Tag Archives: Simona Cavalu

Cataract Surgery in Elderly Patients: Corneal Structure and Endothelial Morphological Changes after Phacoemulsification

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by A.L. Ciorba, A. Teusdea, G. Roiu and Simona Cavalu

The aim of this study was to evaluate the influence of ultrasounds used in phacoemulsification during cataract surgery on the corneal structure and morphology in patients over 65 years. We compared the outcomes of phacoemulsification techniques in terms of corneal cell morphology in
77 patients over 65 years old and 43 patients under 65 years old. Corneal cell density, central corneal thickness and hexagonality were measured preoperatively and post-surgery (at 1 and 4 weeks) by specular microscopy. The effect of gender, axial length and anterior chamber depth on the parameters of corneal endothelium were evaluated. In both groups, a progressive decrease in endothelial cells was observed, starting from the first week post-surgery until the fourth postoperative week. The central
corneal thickness increased in both groups with maximum values at the first week postoperatively, while their initial values were restored in the fourth week post-surgery, with no statistical difference between groups. Statistically significant differences were noticed in terms of cell hexagonality in the group over 65, showing smaller hexagonality at all preoperative and postoperative time points compared to group under 65. Our result highlights the importance of routine specular microscopy
performed before surgery, regardless the age of the patients, with caution and careful attention to the phaco power intensity, ultrasound energy consumption and intraoperative manipulation of instruments, as well as proper use of viscoelastic substances to reduce corneal endothelium damage, especially in elderly patients. Copyright Simona Cavalu et al.

Cataract is considered a multifactorial eye disease, due to the opacification of the lens, that leads to visual impairment when is located in the visual axis. The main cause for cataract development is ageing together with oxidative stress. Risk factors associated with cataract are known to be
educational and income status, smoking, diabetes, ultraviolet radiation, body mass index, estrogen replacement therapy, drug use (non-steroidal antiinflammatory drugs), traumatic injuries, chemicals and local diseases like uveitis or retinal detachment. The surgical technique, the anterior
chamber depth and the use of ophthalmic viscoelastic devices are other factors that can influence the damage degree of the endothelium, as well as the type of IOLs implanted (toric versus non-toric), especially in patients with corneal degeneration or dystrophies. Studies report endothelial cell loss rates from 4% to 25% after phacoemulsification. In this context, the aim of our study was to investigate the main outcomes of cataract surgery in terms of corneal cell density (CD), central corneal thickness (CCT) and hexagonality (HEX) of the endothelial cells in patients over 65 years of age compared to those under 65. Copyright Simona Cavalu et al.

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Representative images of endothelial cell layer (colored dots) 1 week after surgery performed with specular microscopy for (a) patient from group B (≤65 years old) and (b) patient from group A (>65 years old). Legend: CCT—corneal central thickness; CD—cell density; CV—coefficient of variation; HEX—cell hexagonality; N—normal value; MIN—minimum value; MAX—maximum value; AVG—average value; SD—standard deviation of specular image; Pleomorphism—percentage of cells with variation from normal hexagonal shape; Polymegathism—size variation in the endothelial monolayer. Copyright Simona Cavalu et al.
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Combined socio-demographic and clinical characteristics of group A (>65 y) and B (≤65 y). Legend: LE—left eye; RE—right eye; AXL—axial length; ACD—anterior chamber depth. Copyright Simona Cavalu et al.
Copyright Simona Cavalu et al.

Endothelial Cell Density (CD)

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Graphical comparison means of (a) CD_pre, (b) CD_post1w and (c) CD_post4w parameters, with confidence intervals as error-bars, calculated for AgeGrp factor levels. Copyright
Simona Cavalu et al.
Copyright Simona Cavalu et al.
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Graphical comparison means of (a) CCT_pre, (b) CCT_post1w and (c) CCT_post4w parameters, with confidence intervals as error-bars, calculated for AgeGrp factor levels. Copyright
Simona Cavalu et al.
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Graphical comparison means of (a) HEX_pre, (b) HEX_post1w and (c) HEX_post4w parameters, with confidence intervals as error-bars, calculated for AgeGrp factor levels. Copyright Simona Cavalu et al.
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Correlation matrix between measured variables. Legend: AXL, axial length; ACD, anterior chamber depth; CCT_pre, central corneal thickness preoperative; CD_pre, cell density preoperative; HEX_pre, hexagonality of endothelial cells preoperative; CD_loss, cell density loss; U/S, ultrasound energy consumption; EPT, effective phaco time (a) Group A (>65); (b) Group B (≤65). Copyright Simona Cavalu et al.
Copyright Simona Cavalu et al.
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Regression line of prediction of the post-operative (CD_Post1W) cell density (multiple regression FINAL model) for the group B (≤ 65 y). Copyright Simona Cavalu et al.
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Regression line of prediction of the post-operative (CD_Post1W) cell density (multiple regression FINAL model) for the group A (>65 y). Copyright Simona Cavalu et al.

Our study evaluated the influence of phacoemulsification cataract surgery technique on corneal cell density, central corneal thickness and hexagonality preoperatively and postoperatively at 1 and 4 weeks using the specular microscope. The effect of gender, axial length and anterior chamber depth on the parameters of corneal endothelium in the two groups, under and over 65 years of age were evaluated. There were significant differences between the preoperative and postoperative cell density values in both groups, with a progressive loss of cells until the fourth week of evaluation. A significant increase in the CCT was observed in both groups after the first week, while the initial values were restored to almost normal by the fourth week post-surgery, with no statistical difference between group A and B. The cell hexagonality suffered a progressive drop in both groups, with significantly lower HEX values at all preoperative and postoperative times in group A (>65 y). Although the cell density loss was significant in both groups, but more advanced in older patients, accompanied with increased central corneal thickness and reduced values of hexagonality, we had no cases of endothelial decompensation secondary to surgical trauma, characterized by epithelial and subepithelial bullae and stromal edema (also known as bullous keratopathy) that is directly responsible for vision loss following cataract surgery. This outcome can be associated to a good preoperative assessment of the patient, together with the surgeon’s experience and the application of viscoelastic substances with protective role on the corneal endothelium.
Phacoemulsification can and truly does improve the visual function of all patients, under and over 65 years old with senile or presenile cataracts, giving them fully independence for daily activities, improving their life quality. The use of specular microscopy in all patients undergoing phacoemulsification and intraoperative proper use of viscoelastic substances for endothelium protection, as well as making adjustments of intraoperative parameters used for nucleus removal according to preoperative cell density values and caution in terms of phaco power intensity and ultrasound energy, for a successful cataract surgery are all strongly recommended. Copyright Simona Cavalu et al.

The full text of this article at https://www.mdpi.com/2308-3417/9/3/77

Unlocking the Secrets of Post-Surgical Flexion: The Vital Role of Rehabilitation in Total Knee Arthroplasty Recovery

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By Gelu Murvai, Simona Cavalu et al.

This article delves into the critical aspect of postoperative flexion, particularly in the context of total knee arthroplasty (TKA), commonly known as total knee replacement. Postoperative flexion serves as a pivotal metric for assessing the success of the procedure and a patient’s ability to regain functional knee movement. The exploration encompasses the desired range of post-surgery flexion, the surgical factors influencing it, and the indispensable role of rehabilitation in facilitating patients in achieving functional flexion. The study tracks the progress of 713 patients who underwent total knee arthroplasty utilizing the cemented technique, categorizing them based on whether they received non-steroidal anti-inflammatory drugs for postoperative treatment. The monitoring of prosthetic and knee complications, along with the evaluation of the Knee Association Score (KSS) for functional assessment, revealed postoperative complications in approximately 18.23% of the patient cohort. These complications were predominantly associated with a restricted range of motion (ROM < 90°) and patellar clunk syndrome. Significantly, the KSS scale exhibited notable enhancements in the quality of life at 12 months post-surgery compared to preoperative and 6-month assessments. The majority of patients achieved scores classified as good or excellent, underlining the positive impact of the surgical approach and postoperative management on functional outcomes and overall patient well-being. Copyright Gelu Murvai, Simona Cavalu et al.

Prosthetic Complications

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It is evident that there is a 6.1% higher incidence of patients experiencing complications related to normal range of motion in the NSAIDs group, with statistically significant differences (χ2 = 106.511, p = 0.001). Additionally, regarding patellar clunk syndrome, 6.9% more patients were observed in the NSAID group, also showing a statistically significant difference (χ2= 113.230, p = 0.001). Copyright G. Murvai, Simona Cavalu et al.

Knee Complications

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Knee complications, including redness, clunk, rigidity, mechanical issues, septic complications, and fractures, were monitored. Copyright G. Murvai, Simona Cavalu et al.
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A total of 275 patients experienced all six problems, 28 individuals had five different problems, 136 patients were affected by four different types of problems, 84 people had three, and 108 patients had two different types of problems. Additionally, 27 patients had only one of the six problems, while 54 had none of the six types of problems. Copyright G. Murvai,Simona Cavalu et al.

Knee Society Score (KSS)

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Graphical representation of mean KSS scale scores at the study’s commencement and conclusion in preoperative stage (A) and after 6 months (B). Copyright G. Murvai,
Simona Cavalu et al.
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Average values of the KSS scale at the three evaluation time points. Copyright G. Murvai, Simona Cavalu et al.

A comprehensive statistical analysis revealed a noteworthy disparity between the two research groups. The calculated F-statistic (ANOVA) of 4640 yielded a p-value of 0.032, indicating statistical significance. Importantly, the group receiving non-steroidal anti-inflammatory drugs (NSAIDs), denoted as the “N-group”, exhibited significantly superior results in comparison to the counterpart group. The observed statistical difference underscores the impact of NSAIDs on the evolution of KSS, implying a meaningful influence on the functional outcomes measured by this scoring system. These findings suggest a potential association between the use of NSAIDs and enhanced postoperative knee function, providing valuable insights into the factors contributing to the divergent results within the studied patient cohorts. Further investigation into the specific mechanisms and implications of NSAID administration in the context of total knee arthroplasty may illuminate pathways for optimizing patient outcomes and guiding clinical decision making. Copyright G. Murvai, Simona Cavalu et al.

Conclusions

Postoperative complications affected approximately 18.23% of the patient cohort, primarily concerning normal range of motion (ROM < 90°) and patellar clunk syndrome.Inadequate healing, such as excessive scar tissue formation or adhesions around the joint, can limit movement and may necessitate additional surgery.Misalignment of the prosthesis can result in restrictions in the normal movement of the joint, often requiring surgical revision.The group of patients who experienced complications related to normal range of motion recorded a significantly higher percentage (6.1%) when NSAIDs were administered, and in terms of patellar clunk syndrome, the percentage was 6.9% higher in this group.The KSS scale showed a significant increase in the 6-month quality-of-life assessments, with the majority of patients achieving scores considered good or excellent. The mean values of the KSS scale exhibited statistically significant improvements at the two evaluation points, reflecting an enhancement in the patients’ quality of life.Limitations noted include small sample sizes, which could affect the overall results. We did not perform a range of motion analysis due to limited data availability, and the existence of a risk of bias in the articles may influence our results. Short-term follow-up may underestimate side effects. Additionally, clinical heterogeneity could not be completely eliminated, requiring more randomized controlled trials for subgroup analysis. Copyright G. Murvai, Simona Cavalu et al.

Full text available at https://www.mdpi.com/2673-1592/5/4/93

New Sport Supplements Based on Aronia melanocarpa and Bee Pollen to Enhance Antioxidant Capacity and Nutritional Value

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By A. Tirla, Simona Cavalu et al.

Designing New Sport Supplements. Copyright Simona Cavalu et al.

With a high number of athletes using sport supplements targeting different results, the need for complex, natural and effective formulations represents an actual reality, while nutrition dosing regimens aiming to sustain the health and performance of athletes are always challenging. In this context, the main goal of this study was to elaborate a novel and complex nutraceutical supplement based on multiple bioactive compounds extracted from Aronia melanocarpa and bee pollen, aiming to support physiological adaptations and to minimize the stress generated by intense physical activity in the case of professional or amateur athletes. Our proposed formulations are based on different combinations of Aronia and bee pollen (A1:P1, A1:P2 and A2:P1), offering personalized supplements designed to fulfill the individual requirements of different categories of athletes. The approximate composition, fatty acid profile, identification and quantification of individual polyphenols, along with the antioxidant capacity of raw biological materials and different formulations, was performed using spectrophotometric methods, GS-MS and HPLC-DAD-MS-ESI+. In terms of antioxidant capacity, our formulations based on different ratios of bee pollen and Aronia were able to act as complex and powerful antioxidant products, highlighted by the synergic or additional effect of the combinations. Overall, the most powerful synergism was obtained for the A1:P2 formulation. Copyright Simona Cavalu et al.

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FTIR spectra of dried Aronia fruits (a) and bee pollen (b) were recorded using an ATR accessory, along with the ultrastructural details captured via SEM.
Copyright Simona Cavalu et al.
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Experimental design: development of novel sport supplements based on Aronia melanocarpa (A) and bee pollen (P) at different ratios (A1:P1; A1:P2 and A2:P1, v/v). Copyright
Simona Cavalu et al.

The unique combination of Aronia melanocarpa and bee pollen might provide the elements for a personalized sport diet tailored to a particular individual’s requirements. The individualization of supplementation is possible according to each specific sport activity. A better capacity of the organism to cope with intense and repeated training sessions could be sustained via supplementation with the different formulations proposed in our study. The maximum synergism in terms of the antioxidant effect of Aronia melanocarpa in combination with bee pollen was demonstrated for the formulation A1:P2. Further clinical studies are necessary to prove the performances of these formulations in vivo and to monitor possible adverse effects. Copyright Simona Cavalu et al.

Full text at https://www.mdpi.com/1420-3049/28/19/6944#

Emerging Role of GLP-1 Agonists in Obesity: A Comprehensive Review of Randomised Controlled Trials

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By Mihaela Popoviciu, Lorena Paduraru, Galal Yahya , Kamel Metwally  and Simona Cavalu

Obesity is a chronic disease with high prevalence and associated comorbidities, making it a growing global concern. These comorbidities include type 2 diabetes, hypertension, ventilatory dysfunction, arthrosis, venous and lymphatic circulation diseases, depression, and others, which have a negative impact on health and increase morbidity and mortality. GLP-1 agonists, used to treat type 2 diabetes, have been shown to be effective in promoting weight loss in preclinical and clinical studies. This review summarizes numerous studies conducted on the main drugs in the GLP-1 agonists class, outlining the maximum achievable weight loss. Our aim is to emphasize the active role and main outcomes of GLP-1 agonists in promoting weight loss, as well as in improving hyperglycemia, insulin sensitivity, blood pressure, cardio–metabolic, and renal protection. We highlight the pleiotropic effects of these medications, along with their indications, contraindications, and precautions for both diabetic and non-diabetic patients, based on long-term follow-up studies. Copyright Simona Cavalu et al.

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The worldwide prevalence of obesity in 2025: (a) females and (b) males. Obesity refers to BMI ≥ 30 kg/m2. Age-standardized estimates for adults aged 20 years and older. Data obtained from NCD-RisC study. Copyright Simona Cavalu et al.
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Complications of obesity. Copyright: Simona Cavalu et al.

The Emergence of Glucagon-Like Peptide 1 Receptor Agonists and the First Results Obtained upon Administration of Exenatide. Copyright: Simona Cavalu etal.

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The structure of GLP-1-parent.
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Development of exenatide and the corresponding chemical structure.
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Development of Lixisenatide and the corresponding chemical structure.
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Development of liraglutide and the corresponding chemical structure.
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Development of semaglutide and the corresponding chemical structure.
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Development of tirzepatide and the corresponding chemical structure.
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Development of albiglutide and the corresponding chemical structure. Copyright:
Simona Cavalu et al.

The combined central and peripheral actions of GLP-1 RA promote satiety, decrease hunger, and ultimately reduce food intake. While GLP-1 RA-induced deceleration of gastric emptying and occasional nausea may contribute to the weight-reducing effects, they appear to play a minor and temporary role. The inhibition of food intake by GLP-1/RA-mediated GLP-1 has been attributed to both direct central actions, with GLP-1 receptors present in brain regions involved in food intake and energy balance, and indirect pathways via vagal afferents originating in the gut and portal circulation. Copyright: Simona Cavalu et al.

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Distribution of GLP-1 receptors. GLP-1Rs (pdb6X18) mainly exist in the neurons of the brain and the beta cells of the pancreas. Copyright: Simona Cavalu et al.

Table 5. Summary of clinical trials that investigated weight loss using Exenatide. Copyright: Simona Cavalu et al.

StudyDosage/Patients/DurationMain Outcomes, Weight ReductionSide EffectsRef.
Duration-1Exenatide 2 mg/week, against the pre-existing 10 µg/twice per day version
N = 295, 30 weeks		No increased risk of hypoglycaemia and similar reductions in body weightNausea reported in both treatments, but more often for 10 µg/twice per day formulation[136]
Duration-2Exenatide (2 mg once/week) versus maximum approved doses sitagliptin, thiazolidinedione, or pioglitazone, in patients treated with metforminAverage 2.3 kg weight loss in exenatide group, 0.8 kg reduction in sitagliptin group, and 2.8 kg weight gain with pioglitazoneNausea and diarrhea in exenatide and sitagliptin groups[137]
Duration-3Exenatide (2 mg once/week) versus insulin glargine titrated to glucose targets
N = 456, 84 weeks		Average 2.6 kg decrease in bodyweight with exenatide, compared with a 1.4 kg increase with glargine, accompanied by improved glycemic controlNo evidence[145]
Duration-4Exenatide once weekly (EQW) compared with metformin, pioglitazone, and sitagliptin (SITA)
N = 820, 26 weeks		2.0 kg decrease with exenatide versus 0.8 kg reduction with sitagliptin and 1.5 kg increase with pioglitazoneExenatide once weekly induced nausea and diarrhea[146]
Duration-5Exenatide (2 mg once/week)) versus exenatide twice daily (5 µg during 4 weeks followed by 10 µg during 20 weeks) in order to improve glycemic control, body weight, and safety.
N = 252, 24 weeks		Similar reductions in mean body weight from baseline to wk 24 observed in both groups (−2.3 ± 0.4 kg and −1.4 ± 0.4 kg)In both groups, the majority of nausea was transient and mild to moderate in intensity, while the incidence decreased over time[138]
Duration-6Exenatide once weekly (2 mg) versus liraglutide (1.8 mg) once daily in patients with T2DM.
N = 911, 26 weeks		Better body weight reductions in liraglutide group (average 2.68–3.57 kg)Nausea predominantly in exenatide group; diarrhea and vomiting more frequently in the liraglutide group and with decreasing incidence over time in both groups[144]
Duration-7Exenatide 2 mg once weekly or placebo in patients with T2DM inadequately controlled despite titrated insulin glargine ± metformin.
N = 461, 28 weeks		Body weight reduction average of 1.5 kg with exenatide versus placebo.Gastrointestinal and injection-site adverse events more frequent with exenatide + IG than with placebo + IG[140]
Duration Neo-1Exenatide 2 mg once/week, self-injectable Miglyol suspension (QWS-AI) versus exenatide 10 µg twice daily (BID),
N = 375, 28 weeks		Significant body weight was reduced in both groupsGastrointestinal adverse events were reported in 22.7% of patients within exenatide QWS-AI group and 35.6% in exenatide BID group[141,142]
Duration-Neo-2Exenatide 2 mg once-weekly Miglyol suspension for autoinjection (QWS-AI) versus sitagliptin (100 mg once/day oraly) or placebo.
N = 364, 28 weeks		Average 1.12 kg and, respectively, 1.19 kg decrease of bodyweight in exenatide and sitagliptin groups versus 0.15 kg increase in the placeboGastrointestinal events and injection-site reactions[142]

In most studies, GLP-1 levels were not related to insulin concentration or measures of insulin resistance. In preclinical models, GLP-1 mainly demonstrates a stimulatory effect on the HPG axis. Therefore, pharmacological stimulation of the GLP-1R by GLP-1RA might be able to reverse gonadotropin suppression in various states of metabolic imbalance.Due to the complexity of biological systems, the final effect of GLP-1 on the HPG axis is multifactorial and appears to integrate other synergistic and counterbalancing metabolic and endocrine factors. In addition, GLP-1 appears to have a direct anti-fibrotic and anti-inflammatory effect on peripheral reproductive tissues.In conclusion, clinical studies and the anatomical distribution of GLP-1R suggest that GLP-1 might play a vital role as a modulatory signal between metabolic and reproductive systems. Management of comorbidities increasingly common in T2DM patients, such as obesity and liver disease, needs to be better addressed. In this regard, ongoing studies will provide further information on whether the benefits of GLP-1 extend to these indications. Copyright: Simona Cavalu et al.

The full text here: https://www.mdpi.com/1422-0067/24/13/10449

Ganetespib (STA-9090) augments sorafenib efficacy via necroptosis induction in hepatocellular carcinoma: Implications from preclinical data for a novel therapeutic approach

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By Sameh Saber, Alexandru Hasan, Simona Cavalu et al.

Sorafenib, a multikinase inhibitor, is a first-line treatment for advanced hepatocellular carcinoma, but its longterm effectiveness is limited by the emergence of resistance mechanisms. HSP90 plays a critical role in conferring resistance to sorafenib in HepG2 cells under hypoxic
conditions and N-Nitrosodiethylamine-exposed mice. To augment the effects of sorafenib, we investigated the use of ganetespib, an HSP90 inhibitor. We observed a significant negative correlation between LAMP2 and MLKL. Combining ganetespib with sorafenib showed a synergistic cytotoxic effect and resulted in the accumulation of p62 and inhibition of macroautophagy. Copyright Sameh Saber, Alexandru Hasan, Simona Cavalu et al.

Effect of SFB and GTSB on % growth inhibition (A)
and combination index (B). The CTC50 values represent the
concentration at which 50% of cell growth is inhibited and
providing insights into the drugs’ potency against the
tested cells. Copyright Sameh Saber, Alexandru Hasan, Simona Cavalu et al.
Effect of SFB and the combination of GTSB and SFB on the levels of HSP90 (A), HSP70 (B), LAMP2 (C), MLKL (D), and p62 (E) in HepG2 cells. Additionally, a
correlation analysis of the measured parameters was conducted (F). Copyright Sameh Saber, Alexandru Hasan, Simona Cavalu et al.
Effect of SFB and the combination of GTSB and SFB on the number of
nodules per liver (A), liver index (B), AFP (C), and ROS (D). Copyright Sameh Saber, Alexandru Hasan, Simona Cavalu et al.
Liver specimens were stained with H&E to evaluate the effect of different treatments on hepatic architecture and the development of hepatocellular carcinoma. These findings suggest that SFB and the combination of SFB with GTSB may have therapeutic potential for treating HCC. Copyright Sameh Saber, Alexandru Hasan, Simona Cavalu et al.
Correlation analysis for the effect of SFB and the combination of GTSB and SFB on the measured parameters (HSP90, HSP70, LAMP2, MLKL, p62, HIF-1α,
and VEGF).Copyright Sameh Saber, Alexandru Hasan, Simona Cavalu et al.

The proper transportation of proteins across the lysosomal membrane
in the CMA process is dependent on essential components,
including HSP90 and LAMP2. Our study indicates that under hypoxic
conditions, there is a significant upregulation of HSP90 and LAMP2
expression. Our findings suggest that MLKL, which is the mediator of
necroptosis, can be degraded through the CMA pathway under hypoxia.
Furthermore, our preclinical data show that HSP90 plays a critical role
in conferring resistance to SFB under hypoxia by inhibiting necroptosis.
Combining GTSB with SFB may offer a promising therapy for HCC. Copyright Sameh Saber, Alexandru Hasan, Simona Cavalu et al.

Full text available at: https://doi.org/10.1016/j.biopha.2023.114918

Type 1 Diabetes Mellitus and Autoimmune Diseases: A Critical Review of the Association and the Application of Personalized Medicine

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By Mihaela S. Popoviciu, Simona Cavalu et al.

T1DM is frequently associated with other autoimmune illnesses, the most common being autoimmune thyroid disorders affecting more than 90% of people with T1D and autoimmune disorders. Antithyroid antibodies are present in around 20% of children with T1D at the start of the illness and are more frequent in girls. Patients with T1DM often have various other co‐existing multi‐system autoimmune disorders including but not limited to thyroid diseases, parathyroid diseases, celiac disease, vitiligo, gastritis, skin diseases, and rheumatic diseases. Copyright M. S. Popoviciu, Simona Cavalu et al.

Personalized medicine has recently gained favor in the scientific, medical, and public domains, and is frequently heralded as the future paradigm of
healthcare delivery. With the evolution of the ‘omics’, the individualization of therapy is not only closer to reality but also the need of the hour. Copyright: M.S.Popoviciu, Simona Cavalu et al.

Personalized Medicine as an approach to T1DM and associated autoimmune diseases.
T1DM is associated with multiple other endocrine abnormalities—including thyroid, adrenal, gastrointestinal, rheumatological, and dermatological—that might be inapparent initially. Suggested approaches for managing these conditions are based on maintaining an electronic database with a recording of antibody screening and identifying biomarkers. Copyright: M.S. Popoviciu, Simona Cavalu et al.
Table 1. The autoimmune diseases and corresponding antibodies. Copyright: M.S. Popoviciu, Simona Cavalu et al.
Table 2. Personalized medicine and T1DM. Copyright: M.S. Popoviciu, Simona Cavalu et al.

The coexistence of T1DM and another autoimmune disease in the same patient has a major impact on the patient’s quality of life, affecting glucose metabolism, preventing effective insulin therapy, and influencing diabetes control. Hence, we recommend personalizing the treatment of patients with diabetes mellitus in line with their comorbidities and the course of the disease. We also highlight the need for making antibody screening a regular part of disease protocol at least in regions where autoimmune diseases are prevalent, if not everywhere. The co‐existent autoimmune diseases thus treated in tandem can help better patient outcomes. Future studies are warranted to contribute region‐wise prevalence data of these associations as regional and ethnic variations have been largely seen; this data can thus help improve clinical decision making.

Copyright: M.S. Popoviciu, Simona Cavalu et al.

Full text available at: https://www.mdpi.com/2075-4426/13/3/422#B56-jpm-13-00422

Precision Medicine and the future of Cardiovascular Diseases:A Clinically oriented Comprehensive Review

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By Yashendra Sethi, Hitesh Chopra, Simona Cavalu et al.

Copyright Simona Cavalu et al.

The prevalence of CVDs has nearly doubled, increasing from 271 million in 1990 to 523 million in 2019. Additionally, the global trend for the years lived with disability has doubled, increasing from 17.7 million to 34.4 million over the same period. The advent of precision medicine in cardiology has ignited new possibilities for individually personalized, integrative, and patient-centric approaches to disease prevention and treatment, incorporating the standard clinical data with advanced “omics”. These data help with the phenotypically adjudicated individualization of treatment. The major objective of this review was to compile the evolving clinically relevant tools of precision medicine that can help with the evidence-based precise individualized management of cardiac diseases with the highest DALY. The field of cardiology is evolving to provide targeted therapy, which is crafted as per the “omics”, involving genomics, transcriptomics, epigenomics, proteomics, metabolomics, and microbiomics, for deep phenotyping. Research for individualizing therapy in heart diseases with the highest DALY has helped identify novel genes, biomarkers, proteins, and technologies to aid early diagnosis and treatment. Precision medicine has helped in targeted management, allowing early diagnosis, timely precise intervention, and exposure to minimal side effects. Despite these great impacts, overcoming the barriers to implementing precision medicine requires addressing the economic, cultural, technical, and socio-political issues. Precision medicine is proposed to be the future of cardiovascular medicine and holds the potential for a more efficient and personalized approach to the management of cardiovascular diseases, contrary to the standardized blanket approach. Copyright Simona Cavalu et al.

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The OMICS in precision medicine. Copyright Yashendra Sethi, Simona Cavalu et al.
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Timeline of the evolution of precision medicine in cardiology. Copyright Yashendra Sethi, Simona Cavalu et al.
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Domains of precision medicine in cardiology. Copyright Yashendra Sethi, Simona Cavalu et al.

Precision medicine is the future of medicine and holds promise for the more efficient management of cardiovascular diseases, owing to their gradual onset and heterogeneous, multimorbid, and chronic nature. The pathogenesis of these diseases may begin decades before any ultimate disease manifestation. Therefore, the use of precisely targeted tools for diagnosis and personalized treatment can revolutionize management by allowing the prevention, early diagnosis, and tailored treatment of cardiovascular diseases. Precision medicine is still an evolving field and many of the technologies needed for its implementation are in nascent stages. Moreover, the research and data on precision medicine are limited because of the ethical, social, legal, and economic issues, which may have produced an unavoidable bias in this review as well. This review explored the literature on precision medicine in cardiology and tried to outline and summarize the most clinically relevant sections of the evolving field. As we evolve in our capacity and infrastructure to employ tools exploring the genomics, proteomics, and metabolomics of cardiovascular diseases, we stand to see a future where a more precise therapy tailored to the needs, demands and limitations of an individual patient would no longer be a dream but a responsibility. The future of cardiology is here; we need to assimilate, adapt and make it more accessible by educating the providers about the evolving field and making infrastructure more equitable to the public. Copyright Yashendra Sethi, Simona Cavalu et al.

Full access here: https://www.mdpi.com/2077-0383/12/5/1799#

Evaluation of the Corneal Endothelium Following Cataract Surgery in Diabetic and Non-Diabetic Patients

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By Adela Ciorba, Amir M. Abdelhamid, G. Roiu, S. Saber and Simona Cavalu

Figure 1. Representative images of endothelial cell layer (coloured dots) 1 week after surgery performed with specular microscopy for (a) diabetic patient and (b) non-diabetic patient. Copyright: Simona Cavalu et al.

The aim of this study was to evaluate the influence of phacoemulsification cataract surgery on the state of the corneal endothelium in diabetic versus non-diabetic patients. We compared the corneal cell morphology in 48 diabetics with good glycemic control and 72 non-diabetic patients before and after uneventful phacoemulsification. Corneal cell density, central corneal thickness, and hexagonality were measured preoperatively and post-surgery (at 1 and 4 weeks) by specular microscopy. The effect of age, gender, axial length, and anterior chamber depth on the parameters of
the corneal endothelium were evaluated. Copyright Simona Cavalu et al.

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Combined socio-demographic and clinical characteristic of diabetic and non-diabetic groups. Legend: AXL—axial length; ACD—anterior chamber depth. Copyright Simona Cavalu et al.
Correlation matrix between measured variables before the surgery. Legend: AXL, axial length; ACD, anterior chamber depth; CCT_PRE, central corneal thickness preoperative; CD_PRE, cell density preoperative; HEX_PRE, hexagonality of endothelial cells preoperative;
* significance, p < 0.05. Copyright Simona Cavalu et al.
Diagnostics 13 01115 g006
Effect of surgery on central corneal thickness (a), cell density (b), and hexagonality of endothelial cells (c). Copyright Simona Cavalu et al.
Diagnostics 13 01115 g007
Effect of diabetes on surgical outcomes, including central corneal thickness, cell density, and hexagonality of endothelial cells postoperative at 1st week (a) and at 4th week (b). Copyright Simona Cavalu et al.

Conclusions

We noticed significant differences between pre-surgical and postoperative CD values in both diabetic and non-diabetic patients. Despite good glycemic control, diabetic patients had more pronounced morphological abnormalities compared to those of non-diabetics, but visual outcomes after phacoemulsification with IOL implantation were similar in both groups. A drop in the postoperative endothelial density was noted after the first week, in both groups. A significant increase in central corneal thickness was also noted in both groups one week after phacoemulsification, but there was no statistical significance after 4 weeks in the diabetic group. In terms of cell hexagonality, statistically significant differences were noted after 4 weeks in both groups.A major finding in our study is that, although an advanced loss of CD was noted, along with an increased CCT and a reduction of hexagonality (especially in the diabetic group), there were no cases of postoperative bullous keratopathy, probably due to several factors, such as surgeon’s experience and the use of viscoelastic substances with a protective role, as well as a careful preoperative evaluation and a good glycemic index (HbA1c < 7%).We strongly recommend routine specular microscopy and HbA1c evaluation before all cataract surgeries. Regarding intraoperative precautions, a high level of monitoring is necessary in terms of pacho power intensity and ultrasound energy, along with a proper application of the dispersive viscoelastic substances to reduce the risk of endothelial damage for a successful surgical procedure.

Copyright Simona Cavalu et al.

Full text here https://www.mdpi.com/2075-4418/13/6/1115

New Insight and Future Perspectives on Nutraceuticals for Improving Sports Performance of Combat Players: Focus on Natural Supplements, Importance and Advantages over Synthetic Ones

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By A. Tirla, F. Islam, Md. R. Islam, Simona Ioana Vicas and Simona Cavalu

The aim of our work is to highlight nutritional requirements/nutritional assessment, the importance of daily dietary intake in combat players, which increasingly includes a broad range of sports nutrition supplements, and the roles of vitamins, minerals and proteins, combined with antioxidants and strength training, in muscular performance. The main nutrients required in the daily diet of combat players, the mechanisms of action, the main outcomes and possible side effects are summarized. Special attention is paid to natural supplements and their importance and advantages over synthetic ones, along with future trends of development. Copyright Simona Cavalu et al.

Vitamin and mineral classification. Copyright Simona Cavalu et al.
The impact of polyphenols on one’s health and the possibility of improving exercise performance. Copyright Simona Cavalu et al.

The Roles of Antioxidants and Strength Training in Muscular Performance

During exercise, the metabolism is accelerated, oxygen consumption is high and the production of reactive oxygen species (ROS) increases. In addition, after muscle contraction, phospholipase A2 is activated, which initiates a cascade of enzymes, resulting in the formation of ROS. On the one hand, exercise-induced ROS have negative effects, causing altered cellular structure and function and, consequently, muscle damage, immune dysfunction and fatigue. On the other hand, ROS formation after exercise can also have beneficial effects, such as stimulating glycogen resynthesis and reducing susceptibility to infection while initiating and promoting adaptative responses to training, thus enhancing athletic performance. Copyright Simona Cavalu et al.

Nanotechnological Tools for Nutraceuticals and Functional Foods

The individualization of meals based on biometric data has become a significant trend in modern nutrition. This study has been spurred on by technological developments in various domains, including analytical instrumentation, biotechnology, computers and data processing . As a result, personalized dietary gadgets tailored to a particular individual’s requirements could be developed. Personalized diets could advise a person to eat more of certain food groups. On the other hand, several food and nutrition companies work on functional foods and beverages enhanced with specific nutrients or nutraceuticals. Many of these things will be dependent on colloidal delivery technologies, which can incorporate a range of bioactive compounds into foods and beverages. These individualized diets can be adapted to an individual’s needs in various ways, including combining multiple nutrients in a single delivery system or integrating multiple delivery systems containing different nutrients, as we will see later. However, there is presently no information on the appropriate type and concentration of various bioactive components
to distribute to specific individuals, which will have to be discovered when colloidal delivery systems are constructed. As a result, future research should consider this much broader perspective, including advanced development in designing nanostructures with new or significantly improved attributes for the implementation of novel nutraceuticals in sports nutrition. Copyright Simona Cavalu et al.

Full text at https://www.mdpi.com/2076-3417/12/17/8611

Carbocisteine as a Modulator of Nrf2/HO-1 and NFκB Interplay in Rats: New Inspiration for the Revival of an Old Drug for Treating Ulcerative Colitis

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By A. M. Abdelhamid, Simona Cavalu, Sameh Saber et al.

The current therapies for UC lack relative effectiveness and are associated with adverse effects. Therefore, novel therapeutic options should be developed. It has been well documented that modulating the Nrf2/NFκB is a promising therapeutic target in inflammation. Carbocisteine is a mucoregulatory medication and its efficacy in COPD was found to be more closely related to its antioxidant and anti-inflammatory properties.
Carbocisteine has not yet been examined for the management of UC. Hence, our approach was to investigate the potential coloprotective role of carbocisteine in acetic acid-induced colitis in rats. Copyright Sameh Saber, Simona Cavalu et al.

Effect of CRBST 250 and 500 mg/kg on colon weight/length ratio (A); DAI (B); MDI (C); and the colon pictures (D) in rats with AA-induced UC. Results
in figure (A) are shown as the mean ± SD and in figure (B,C) are shown as the median ± interquartile range (n = 6). Normal, normal
control rats administered the vehicle; CRBST 500, normal rats administered carbocisteine (500 mg/kg); UC, AA-induced UC rats administered the vehicle; UC/CRBST
250, AA-induced UC rats treated with carbocisteine (250 mg/kg); UC/CRBST 500, AA-induced UC rats treated with carbocisteine (500 mg/kg). Copyright Simona Cavalu, Sameh Saber et al.
Effect of CRBST 250 and 500 mg/kg on histopathological characteristics and histopathological score in rats with AA-induced UC. Representative histological appearance of colon tissue specimens stained with H&E from Normal (A) and CRBST 500 (B) control groups, Colonic sections from UC group (C) showing deepithelialization,erosions (green arrow), disrupted mucosa (M) and submucosa (SM), inflammatory cell infiltration (blue diamond), edema (orange double arrow), congestion (brown arrow) and complete necrosis of the crypts (blue arrow); Colonic sections from UC/CRBST 250 (D) and UC/CRBST 500 (E) showing a moderate restoration of architecture. Copyright Simona Cavalu, Sameh Saber et al.
The proposed mechanism of action of carbocisteine. Copyright Simona Cavalu, Sameh Saber et al.

Nrf2 and NF-κB are the two key transcription factors that regulate cellular responses to oxidative stress and inflammation respectively. Pharmacological and genetic studies indicate
functional cross-talk between these two critical pathways. Carbocisteine, at
doses that are quite higher than the human effective dose, inhibited oxidative stress, inflammatory response, and apoptosis in acetic acid-induced colitis in rats through activating Nrf2 and suppressing NFκB. The current study provides a potential basis for repurposing the safe and
commonly used mucoregulator, carbocisteine, for the treatment of UC. However, further research into other pathways that run parallel to those proposed in the current study is required to assess the reliability of carbocisteine as a treatment for UC. Copyright Simona Cavalu, Sameh Saber et al.

Full text available at https://doi.org/10.3389/fphar.2022.887233

Preparation, Physico-Chemical Properties and Biomedical Applications of Nanoparticles

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Edited By Simona Cavalu

Nowadays, the impact of nanotechnology on applications in medicine and biomedical sciences has broader societal and economic effects, enhancing awareness of the business, regulatory, and administrative aspects of medical applications. The selected papers included in the present special issue gives readers a critical, balanced and realistic evaluation of existing nanomedicine developments and future prospects, allowing practitioners to plan and make decisions. The topics covers the use of nanoparticles and nanotechnology in medical applications including biomaterials for tissue regeneration, diagnosis and monitoring, surgery, prosthetics, drug delivery systems, nanocarriers, wound dressing. I would like to express my gratitude to all contributors to this issue, who have given so much of their time and effort to help create this collection of high quality papers.

Copyright Simona Cavalu

Bioactive Based Nanocarriers for the Treatment of Viral Infections and SARS-CoV-2

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By Ravi Goyal, Abhijit Dey, Md. Habibur Rahman, Simona Cavalu et al.

The spread and pandemic of viral diseases are becoming a major threat to public health and a burden on the financial prosperity of communities worldwide. In recent years, SARS-CoV-2 has made a dramatic lifestyle change. This has promoted scientists not to use synthetic anti-virals, such as protease inhibitors, nucleic acid analogs, and other anti-virals, but to
study less toxic anti-viral phytomolecules. An emerging approach includes searching for eco-friendly therapeutic molecules to develop phytopharmaceuticals. This article briefly discusses numerous bioactive molecules that possess anti-viral properties, their mode of action, and possible applications in treating viral diseases, with a special focus on coronavirus and various nano-formulations used as a carrier for the delivery of phytoconstituents for improved bioavailability. Copyright Simona Cavalu et al.

Structure of Coronavirus. Copyright Simona Cavalu et al.
The activity of anti-viral phytomolecules with their mechanisms of action. Copyright
Simona Cavalu et al.
Proposed mechanism of action of various essential oils for anti-viral activity. Copyright Simona Cavalu et al.
Role of enzyme and protein inhibitors in SARS-CoV. Copyright Simona Cavalu et al.
Herbs are effective in preventing COVID-19 infection. Copyright Simona Cavalu et al.

Various delivery systems, such as self-nano emulsifying drug delivery systems (SNEDDS), hydrogels, phytosomes, microspheres, transferases, etc., have been used for the delivery of phytoconstituents with anti-viral potential. These nanoformulations displayed numerous effects, such as improved oral solubility, systemic bioavailability, delayed metabolism, and enhanced therapeutic activity. Copyright Simona Cavalu et al.

Different nano-formulations for the delivery of phytoconstituents with anti-viral potential. Copyright Simona Cavalu et al.

Numerous natural products, along with essential oils and herbal constituents isolated from them, are observed to possess the strong potential to fight against viral infections and their discoveries can provide further help in synthesizing derivatives and therapeutic leads. As large research studies in this area are only preliminary, further details of experimentation in characterizing the bioactive constituent, defining the principal mechanisms, as well as evaluating the efficacy and in vivo studies, are encouraged to develop more therapeutically sound anti-viral therapies through natural products. Furthermore, additional studies need to be performed to explore the possibility of developing combination therapies with other natural agents, such as polyherbal nanoformulations with site-specificity, which may help in reducing the risk of developing drug-resistant viruses. Phytopharmaceuticals will continue to play an important role and contribute to novel nanoformulations as a carrier for safe and cost-effective
delivery systems. Copyright Simona Cavalu et al.

Full text available at : https://www.mdpi.com/2079-4991/12/9/1530/htm

Natural Small Molecules in Breast Cancer Treatment: Understandings from a Therapeutic Viewpoint

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By Md. R. Islam, F. Islam, MH. Nafady, T B. Emran, Simona Cavalu &al

Breast cancer (BrCa) is considered a global public health concern ; it is the second most widely diagnosed cancer and a prominent cause of mortality in women. As a result, to reduce the number of BrCa-related mortality, effective BrCa therapies are necessary. Furthermore, people of certain races or ethnicities are more likely to develop BrCa. African American women under the age of 40 are twice as likely to develop BrCA as white women of the same age. Females of American, African, and Hispanic heritage can be identified with aggressive and severe types of BrCa. Copyright Md.R. Islam, F. Islam, MH Nafady, Simona Cavalu & al.

Molecular subtypes of breast cancer and triple-negative breast cancer types are depicted.
Overall survival (for breast cancer subtypes) and relapse-free survival (for TNBC subtypes) are used to distinguish the subtypes. Copyright Md.R. Islam, F. Islam, MH Nafady,
Simona Cavalu & al.

Risk Factors for Breast Cancer. Despite the urgent need for effective and novel therapies, there is considerable concern in identifying BrCa risk factors and improving chemo-preventive and lifestyle adjustment actions that can help decrease the impact of the disease. Although BRCA1 and BRCA2, as tumor-suppressor proteins, signify less than 10% of cases; their
discovery has overwhelmingly influenced patient treatment. Other risk factors linked with ER-positive BrCa progress, for example early menarche, early thelarche, and first pregnancy at a later age, are less well characterized and may also be linked to increased estrogen exposure. Obesity and metabolic syndrome, additionally, have been recently established as significant BrCa risk factors, a link that is particularly noteworthy considering the present obesity epidemic. Increased influence of adipokines and inflammatory cytokines, as well as increases in circulating insulin and insulin-like growth factors, local estrogen synthesis in adipose tissue, and the impact of circulating insulin and insulin-like growth factors, are all thought to play a role in disease development. Copyright Md.R. Islam, F. Islam, MH Nafady, Simona Cavalu & al.

Natural Compounds against Breast Cancer: Quercetin, Tetrandrine, Thymoquinone, Resveratrol, Honokiol, Garcinol, Biochanin A, Lycopene, Shikonin, Sulforaphane, Echinacea, Garlic, Turmeric, Burdock, Carotenoids, Green Tea.

Multifunctional effects of natural compounds on breast cancer. Some of these compounds may have synergistic impacts or aid in the fight against multidrug resistance. Natural compounds may play an important role in treating and preventing BrCa in the not-too-distant future, given all of these factors.Copyright Md.R. Islam, F. Islam, MH Nafady, Simona Cavalu & al.

Natural substances have been shown through multiple investigations
to decrease carcinogenesis and reverse cancer growth by triggering apoptosis and cell cycle arrest. They impact tumor cells by interfering with cell death pathways such as extrinsic and intrinsic apoptosis and autophagy. These compounds inhibit cancer cell proliferation through these processes while causing minimal harm to normal cells. Natural compounds are currently being explored in clinical practice because of their anticancer
and apoptotic effects and low toxicity. Many of these substances will likely be used to treat BrCa as they have previously been found to have significant effects against various illnesses]. Finally, the natural compounds mentioned are just a fraction of the many chemicals that have been revealed to have anti-BrCa properties. Through the potential of these compounds, researchers are getting closer to finding a cure for BrCa. These compounds
have the potential to lower BrCa-related mortality and help people live longer across the world. Therefore, natural substances should continue to be investigated as an option for BrCa therapy. Copyright Md.R. Islam, F. Islam, MH Nafady, Simona Cavalu & al.

Full text available at https://www.mdpi.com/1420-3049/27/7/2165

Septic cardiomyopathy: The Value of Immuno-histochemical Diagnostics and Role of Lipopolysaccharide Receptor (CD14)

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By P. M. Reil, T. T. Maghiar, N. Vîlceanu, A. Pascalau, Claudia Teodora Judea Pusta, F. Marcu , Simona Cavalu and Ovidiu Pop

The aim of this our study was to determine any significance of the mCD14 and sCD14 levels in the septic cardiomyopathy, and to evaluate the correlation with lipopolysaccharide-binding protein (LBP) by means of immuno-histological examinations.

(A,B) H&E normal aspects of the control group, showing cardiac muscle fibers with interstitial edema and inflammatory infiltrate. (A) Cardiac muscle fibers with small nuclei located centrally—white arrows (magnification 100×). (B) The nuclei of the fibers are enlarged in volume, revealing cellular suffering—white arrows (magnification 200×). (C) The negative expression of CD14 in a specimen belonging to the control group. The causes of death in the control group were not related to heart disease (magnification 100×). (D) Immunohistochemical image of numerous myocardial fibers with inflammatory cells intercalated, with the membrane marked in brown, showing low CD14 expression (<10%)—white arrows (magnification 40×). (E) Immunohistochemical image of the myocardial cells, with numerous inflammatory cells intercalated and membranous immune expression of CD14 marked in brown and white arrows. Its expression is revealed mainly on the macrophage membrane surface, but also minimally distributed on the neutrophil surface of mCD14. No expression is seen in the blood vessels—yellow arrows (magnification 40×). (F) Immunohistochemical image of a blood vessel located intramuscularly—yellow arrows. In the vessel’s lumen there can be noticed granular areas of extracellular, soluble CD14 (brown color) along with monocytes and neutrophils (mCD14)—white arrows (magnifications 40×). Copyright P. M. Reil, T. T. Maghiar, N. Vîlceanu, A. Pascalau, Claudia Teodora Judea Pusta, F. Marcu , Simona Cavalu and Ovidiu Pop

The study showed: 1) a positive association between markedly increased values of CD14 and an adverse patient evolution; 2) significant increase in the level of membranous and soluble CD14 surface protein in the study group; 3) tendency for higher values in relation to older patients, but without statistical significance; 4) no statistically relevant difference regarding the patient’s gender, provenance, or infection site; 5) a positive association between cellular expression (membranous, mCD14) and intravascular (soluble, sCD14) levels; 6) CD14 plays a double role: (a) as a component of the innate immune system, a pattern recognition receptor (PRR) proposed to bind conserved molecular structures on microbes (pathogen-associated molecular patterns, PAMPs, e.g., LPS); (b) as an active agent involved in the apoptotic cell cleaning process. Apoptotic cell-associated molecular patterns (ACAMPs) interfere with PRR and LPS-like
structures, as revealed on apoptotic cells. (Copyright P. M. Reil, T. T. Maghiar, N. Vîlceanu, A. Pascalau, Claudia Teodora Judea Pusta, F. Marcu , Ovidiu Pop and Simona Cavalu)

We suggest that a large amount of sCD14 detected in the myocardial tissue will activate the mCD14–TRL4–LBP–LPS complex and further induce an inadequate immune response, resulting in severe heart damage. A higher amount of LPS will induce more significant heart damage. Identification of the presence of mCD14 and sCD14 in the myocardium tissue can allow the indubitable diagnosis of septic cardiomyopathy. (Copyright P. M. Reil, T. T. Maghiar, N. Vîlceanu, A. Pascalau, Claudia Teodora Judea Pusta, F. Marcu , Simona Cavalu and Ovidiu Pop)

Full text available at: https://www.mdpi.com/2075-4418/12/4/781/htm

Nifuroxazide-loaded cubosomes for pulmonary delivery attenuates bleomycin-induced lung fibrosis

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By Sameh Saber, Mohamed Nasr, Simona Cavalu & al

This study highlights the importance of cubosomes as a drug delivery
system in enhancing the bioavailability of nifuroxazide (NXZD), a poorly soluble STAT3 inhibitor. NXZD loaded cubosomes (NXZD-LC) were in vitro and in vivo evaluated. In vitro, cubosomes presented a poly-angular
nanosized particles with a mean size and zeta potential of 223.73 ± 4.73 nm and 20.93 ± 2.38 mV, respectively. The entrapment efficiency of nifuroxazide was 90.56 ± 4.25%. The in vivo pharmacokinetic study and the
lung tissue accumulation of NXZD were performed by liquid chromatography-tandem mass spectrometry after oral administration to rats. The nanoparticles exhibited a two-fold increase and 1.33 times of bioavailability and lung tissue concentration of NXZD compared to NXZD dispersion, respectively. In view of this, NXZD-LC effectively
attenuated PF by targeting STAT3 and NF-κB signals. Copyright Sameh Saber, Mohamed Nasr, Simona Cavalu & al.

NXZD-loaded cubosomes; Mean plasma concentration-time profile (mean ± SD) after intra-gastric administration of NXZD suspension and
NXZD-loaded cubosomes. Copyright Sameh Saber, Mohamed Nasr, Simona Cavalu & al.
Effect of NXZD suspension and NXZD-loaded cubosomes on lung tissue histological features in intratracheal bleomycin-exposed rats. BLMC group exhibited a massive
inflammatory-cell infiltration (arrows), alveolar wall thickening (arrowhead), and the highest inflammation score. BLMC + NXZD showed moderate
inflammatory-cell infiltration (arrow) and alveolar wall thickening (arrowhead) and a non-significant difference in the inflammatory score compared with that of
BLMC group.Copyright Sameh Saber, Mohamed Nasr, Simona Cavalu & al.
Effect of NXZD suspension and NXZD-loaded cubosomes on lung tissue fibrotic changes in intratracheal bleomycin-exposed rats: significant decrease in the A% of
fibrosis compared with that of BLMC group.Copyright Sameh Saber, Mohamed Nasr,
Simona Cavalu & al.
Effect of NXZD suspension and NXZDloaded
cubosomes on the levels of LDH (a)
and BALF total protein (b) in intratracheal
bleomycin-exposed rats. Copyright Sameh Saber, Mohamed Nasr, Simona Cavalu & al.
Effect of NXZD suspension and NXZDloaded
cubosomes on MDA (a), NOx (b), GSH
(c) and SOD (d) in intratracheal bleomycinexposed
rats. Copyright Sameh Saber, Mohamed Nasr, Simona Cavalu & al.
Effect of NXZD suspension and NXZD-loaded cubosomes on COL1A1 mRNA expression (a), hydroxyproline (b) and ICAM-1 (c) in lung tissue in intratracheal
bleomycin-exposed rats. Copyright Sameh Saber, Mohamed Nasr, Simona Cavalu & al.
Effect of NXZD suspension and NXZD-loaded
cubosomes on TLR4 mRNA expression (a), TLR4 (b),
IL-6 (c), TNF-α (d) and MCP-1 (e) in lung tissue in
intratracheal bleomycin-exposed rats. Copyright Sameh Saber, Mohamed Nasr,
Simona Cavalu & al.
Effect of NXZD suspension and NXZDloaded
cubosomes on TGF-β1 mRNA expression
(a), TGF-β1 (b), PDGF-BB (c) and TIMP-1
(d) in intratracheal bleomycin-exposed rats. Copyright Sameh Saber, Mohamed Nasr,
Simona Cavalu & al.
Effect of NXZD suspension and NXZD-loaded cubosomes on NF-κB p65 DNA binding activity (a), STAT3 mRNA expression (b) and p-STAT3 (Tyr 705) (c) in
intratracheal bleomycin-exposed rats. Copyright Sameh Saber, Mohamed Nasr,
Simona Cavalu & al.

Nifuroxazide showed a potential anti-inflammatory effect, improved antioxidant defense, and suppressed fibrogenic mediators in the lung tissue. To conclude, cubosomes represent an advantageous pharmaceutical delivery system for enhancing pulmonary delivery of poorly soluble drugs. Additionally, since NXZD does induce cross-resistance to other antibacterial agents and does not adversely affect the physiological intestinal bacterial flora, repurposing NXZD as an antifibrotic agent is a promising challenge and new therapeutic approach for unmet therapeutic needs. Copyright Sameh Saber, Mohamed Nasr, Simona Cavalu & al.

Full text at

https://www.sciencedirect.com/science/article/pii/S0753332222001196