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

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

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.
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Effect of surgery on central corneal thickness (a), cell density (b), and hexagonality of endothelial cells (c). Copyright Simona Cavalu et al.
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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

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

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

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

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

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

Green Metallic Nanoparticles: Biosynthesis to Applications

By H. Chopra, T. Bin Emran, Simona Cavalu & al

Algae, plants, bacteria, and fungus have been employed to make energy-efficient, low-cost, and nontoxic metallic nanoparticles in the last few decades. Despite the environmental advantages of using green chemistry-based biological synthesis over traditional methods as discussed in this article, there are some unresolved issues such as particle size and shape consistency, reproducibility of the synthesis process, and understanding of the mechanisms involved in producing metallic nanoparticles via biological entities. Consequently, there is a need for further research to analyze and comprehend the real biological synthesis-dependent processes. Copyright: H. Chopra, Simona Cavalu & al

Schematic representation of biosynthesis of nanoparticles from plants. Copyright H. Chopra, Simona Cavalu & al.

FACTORS AFFECTING BIOSYNTHESIS OF NANOPARTICLES: Nanoparticles creation from biological extracts may also be affected by reaction conditions. Studies have shown that a reaction solution’s pH has a significant impact on the production of the nanoparticles that result. The form and size of the generated nanoparticles may be affected by changes in the reaction pH. When comparing lower acidic pH values to higher acidic pH values, bigger particles are produced. The bigger particles (25–85 nm) were generated at pH two whereas the smaller particles (5–20 nm) were created at pH three and four in a research using Avena sativa biomass (Armendariz et al., 2004). Particle aggregation may have been caused by the lack of functional groups at pH 2, according to the researchers. The bacteria Rhodopseudomonas capsulate was shown to produce gold nanoparticles in a similar manner. It was discovered that, with a pH rise of 7, spherical particles measuring 10–20 nm were present. Nanoplates were formed when the reaction pH was lowered to 4 (He et al., 2007). Copyright: H. Chopra, Simona Cavalu &al.

Antibacterial action of silver nanoparticles via ROS pathway. In comparison to Gram-negative bacteria, Gram-positive bacteria have a stronger cell wall due to a lower concentration of lipopolysaccharides, making them a more formidable barrier to the entry of AgNPs. Gram-negative bacteria’s cell walls and membranes are thinner due to more lipopolysaccharides a and less peptidoglycan. They adhere to AgNPs due to their composition, stability, and negative charge. Because AgNPs have an electrical affinity to bacteria, they may be used to kill them, as was previously stated (Abbaszadegan et al., 2015).Copyright: H. Chopra,
Simona Cavalu & al.
Anticancer effect of zinc nanoparticles. Targeted medication delivery
using ZnO nanoparticles provides new options for cancer
therapy that are both safer and more effective. Zinc oxide
nanoparticles (ZnO) may be used as nanocarriers for various
chemotherapeutic drugs that synergistically impact cancer cells. Copyright: H. Chopra, Simona Cavalu & al.

RECYCLABILITY AND REUSABILITY OF
GREEN-SYNTHESIZED NANOPARTICLES: The areas of materials engineering and nanotechnology are increasingly concerned with sustainability techniques, frameworks, and metrics in an attempt to mitigate
environmental and health concerns connected with the manufacturing, use, and disposal of innovative nanomaterials (Dhingra et al., 2010). Veisi et al., synthesized Ag nanoparticles based on Thymbra spicata, the plant being rich source of thymol, carvacrol and myrcene (Veisi et al., 2018). In spite of the significant catalytic activity of Ag Nanoparticles/Thymbra. When Ag NPs/Thymbra were separated and reapplied in RhB and MB colour degradation, their recycling efficiency was determined correspondingly. Similarly, researchers developed copper nanoparticles using Commersonia bartramia extract and immobilized using Al2O3 surface (Nasrollahzadeh et al., 2019). The catalyst was able to show significant changes upto 7th cycle, for reduction of 2,4-dinitrophenylhydrazine. Copyright: H. Chopra, Simona Cavalu & al.

Despite the environmental advantages of using green chemistry based biological synthesis over traditional methods as discussed in this article there are some unresolved issues such as particle size and shape consistency, reproducibility of the synthesis process, and understanding of the mechanisms involved in producing metallic nanoparticles via biological entities. Therefore, there is a need for further research to analyze and
comprehend the real biological synthesis dependent processes. This is a vastly untapped subject that needs much more research investment to properly leverage the green manufacturing of metallic nanoparticles through living entities. Copyright: H. Chopra, Simona Cavalu &al.

Full text at https://www.frontiersin.org/articles/10.3389/fbioe.2022.874742/full

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

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

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

Therapeutic efficacy of Clompanus pubescens leaves fractions via downregulation of neuronal cholinesterases/Na+-K+ATPase/IL-1 β, and improving the neurocognitive and antioxidants status of streptozotocin-induced diabetic rats

By A. S. Onikanni, Simona Cavalu, G. El-Saber Batiha et al.

Clompanus pubescens leaf fractions displayed
hypoglycemic effect in streptozotocininduced
diabetic rats (A) Fasting blood
glucose level (FBGL) and (B) body weight of
streptozotocin-induced diabetic rats. Copyright A. S. Onikanni, Simona Cavalu, G. El-Saber Batiha et al.
Clompanus pubescens leaf fractions improved the neuronal antioxidant status of streptozotocin-induced diabetic rats. Effect of C. pubescens leaf fractions on the
level of (A) GSH and activities of (B) SOD (C) CAT, (D) GST, and (E) GPx in the brain of streptozotocin-induced diabetic rats. Copyright A. S. Onikanni, Simona Cavalu, G. El-Saber Batiha et al.
The level of Interleukin-1 β (IL-1 β) in streptozotocin-induced diabetic
rats after administration of Clompanus pubescens leaf fractions.Copyright A. S. Onikanni, Simona Cavalu, G. El-Saber Batiha et al.
Clompanus pubescens leaf fractions ameliorates
cognitive deficits in streptozotocin-induced diabetic rats.
Effect of C. pubescens leaf fractions on (A) Y-Maze test, and
(B) novel object recognition (NOR) test.Copyright A. S. Onikanni, Simona Cavalu, G. El-Saber Batiha et al.
3D and 2D views of the receptor-ligand interactions between butyrylcholinesterase (BChE) and the identified
compounds from ethyl acetate fraction of Clompanus pubescens. Copyright A. S. Onikanni, Simona Cavalu, G. El-Saber Batiha et al.
3D and 2D views of the receptor-ligand interactions between acetylcholinesterase (AChE) and the identified compounds
from ethyl acetate fraction of Clompanus pubescens. Copyright A. S. Onikanni,
Simona Cavalu, G. El-Saber Batiha et al.
2D view of the receptor-ligand interactions between sodium-potassium adenosine triphosphatase (Na+-K+-ATPase) and the identified
compounds from ethyl acetate fraction of Clompanus pubescens. Copyright A. S. Onikanni,
Simona Cavalu, G. El-Saber Batiha et al.
In silico gastrointestinal absorption and Blood Brain Barrier Penetration
modelling of the identified compounds from the ethyl acetate fraction of
Clompanus pubescens. Copyright A. S. Onikanni,
Simona Cavalu, G. El-Saber Batiha et al.

Herein, we evaluated the neuroprotective and antioxidant properties of different fractions (ethyl acetate, N-butanol and residual aqueous) of Clompanus pubescens leaves in streptozotocin (STZ)-induced diabetic rats. Our results revealed a significant elevation in the levels of blood glucose, pro-inflammatory cytokines, lipid peroxidation, neuronal activities of acetylcholinesterase, butyrylcholinesterase, nitric oxide, epinephrine, norepinephrine, and Na+/K+-ATPase in diabetic non treated rats. In addition, decreased levels of enzymatic and non-enzymatic antioxidants were observed. Treatment with different fractions of C. pubescens leaves resulted in significant reversal of the biochemical alteration
and improved the neurocognitive deficit in STZ induced diabetic rats. Copyright A. S. Onikanni, Simona Cavalu, G. El-Saber Batiha et al.

Full text at https://www.sciencedirect.com/science/article/pii/S0753332222001184?via%3Dihub

Evolution of diagnostic methods for Helicobacter pylori infections: from traditional tests to high technology, advanced sensitivity and discrimination tools

By A. I. Cardos, Simona Cavalu et al.

Invasive and noninvasive diagnostic tools for H. pylori. Copyright Simona Cavalu et al.
Invasive and noninvasive diagnostic tools for H. pylori. Copyright Simona Cavalu et al.

This paper aims to expose the diagnosis methods for H. pylori that are currently available, high-lighting their assets and limitations. The perspectives and the advantages of nanotechnology along with the concept of nano(bio)sensors and development of lab-on-chip devices as advanced tools for H. pylori detection, differentiation and discrimination is also presented, by emphasizing multiple advantages: simple, fast, cost effective, portable, and miniaturized, small volume of sam-ples required, highly sensitive and selective. It is generally accepted that intelligent sensors devel-opment will completely revolutionize the acquisition procedure and medical decision in the framework of smart healthcare monitoring system. Copyright Simona Cavalu et al.

Histological imaging for H. pylori
Gastric mucosa showing reduced cytoplasmic mucin (blue arrow), reactive epithelial changes (red arrow) and a mix between acute inflammatory cells and chronic inflammatory cells (H&E, ob100x); b) Gastric mucosa showing reduced cytoplasmic mucin (blue arrow), lymphocytes and plasma cells (red arrow). Histological imaging for H. pylori (yellow arrow). H&E, 200x ob; c) Clusters of cells with intracellular H. pylori were widely distributed within the lamina propria (blue arrow) and were especially abundant just below the superficial epithelial cell layer of the gastric mucosa (red ar-row). IHC 100x ob. Images from private collection, Prof. dr. Ovidiu Pop, unpublished. Copyright Simona Cavalu, Ovidiu Pop et al.

The limitations of traditional tools have promoted the development of innovative methods for the rapid and cost-effective diagnosis of H. pylori infection. These novel biosensors, coupled with nanomaterials, may provide a hybrid device with unique physical and chemical properties, which make them an excellent label and sensing device for point of care (POC) diagnosing of H. pylori. Copyright Simona Cavalu et al.

In recent years, the development of nanotechnology allowed the nano-biosensor to be connected to wearable devices, meanwhile, the signal/information is transmitted wirelessly to a smartphone, leading to a smart healthcare monitoring system. The combination between using a smartphone as a reader and the nano-biosensors as a detection method has been already investigated for biomedical applications (detection of various pathogens, chemical substances, cells, etc.), the integration of smart instruments, and nanobiotechnology, leading to all-in-one sensing systems used as portable self-diagnosis devices. Copyright Simona Cavalu et al.

Full text at https://doi.org/10.3390/diagnostics12020508

New therapeutic target in inflammation: Emerging role of dapagliflozin in overcoming lipopolysaccharide-mediated lung injury

By E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.

Effect of dapagliflozin (5 and 10 mg/kg) on the histological features of LPS-induced lung injury. Lung specimens of the Control or DPGZ animals exhibited no
histological alterations of normal bronchioles (B), normal alveoli (A), normal airspaces (AS), and normal alveolar wall thickening (arrowhead). However, LPSexposed
rats exhibited massive inflammatory-cell infiltration of neutrophils, macrophages and lymphocytes (arrows), alveolar wall thickening (arrowheads),
fibrinous exudates (star) and the highest of both the inflammation score and the lung lesion distribution score. In contrast, DPGZ at both the lowest dose and
particularly the highest dose resulted in a marked improvement in lung histological features of lower degree of inflammatory-cell infiltration (arrows) and alveolar
wall thickening (arrowheads) and a significant decline in both the inflammation score and the lung lesion distribution score compared to LPS-exposed rats. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.
Effect of DPGZ (5 and 10 mg/kg) on the level of (A) SOD, (B) CAT, (C) GSH, (D) NOx, and (E) MDA in rats with LPS-induced ALI. SOD: superoxide dismutase, CAT: catalase, GSH: reduced glutathione, NOx: nitric oxide, MDA: malondialdehyde, DPGZ: dapagliflozin, LPS:
lipopolysaccharides. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.

Effect of dapagliflozin treatment on inflammatory markers: MPO activity as well as MCP-1, IL-1β, IL-18, and TNF-α levels. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.
Effect of DPGZ (5 and 10 mg/kg) on p-AMPK/t-AMPK ratio in rats with LPS-induced ALI.
p-AMPK: phosphorylated adenosine monophosphate phosphate kinase, t-AMPK: total adenosine monophosphate phosphate kinase, DPGZ: dapagliflozin, LPS: lipopolysaccharides. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.
Effect of dapagliflozin treatment on NLRP3 levels, NLRP3 gene expression, and caspase-1 activity. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.
Effect of dapagliflozin treatment on NF-kB P65 binding activity and NFĸB p65 (pSer536) levels in rats with LPS-induced ALI. NF-kB: nuclear factor kappa B, DPGZ: dapagliflozin, LPS: lipopolysaccharides. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.

Acute lung injury (ALI) is one the most common causes of morbidity and mortality in critically ill patients. In this study, we examined for first time the role of dapagliflozin (DPGZ) in lipopolysaccharide (LPS)-induced ALI in rats and determined the underlying molecular mechanisms by evaluating the effects of DPGZ on adenosine monophosphate kinase (AMPK), nuclear transcription factor kappa B, nucleotide-binding and oligomerization domain-like receptor 3 inflammasome activation. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.

Full text available at : https://www.sciencedirect.com/science/article/pii/S0753332222000166#fig0005

Phyto-Nanotechnology for the Treatment of Neurodegenerative Disorders

By T. Bhattacharya, G. A. Borges e Soares, H. Chopra, Md. M. Rahman, Z. Hasan, S. S. Swain and Simona Cavalu

Materials 15 00804 g001
Neurodegenerative diseases and the types of neurons affected. Copyright T. Bhattacharya, Simona Cavalu et al.

The strategies involved in the development of therapeutics for neurodegenerative disorders are very complex and challenging due to the existence of the blood-brain barrier (BBB), a closely spaced network of blood vessels and endothelial cells that functions to prevent the entry of unwanted substances in the brain. The emergence and advancement of nanotechnology shows favourable prospects to overcome this phenomenon. Engineered nanoparticles conjugated with drug moieties and imaging
agents that have dimensions between 1 and 100 nm could potentially be used to ensure enhanced efficacy, cellular uptake, specific transport, and delivery of specific molecules to the brain, owing to their modified physico-chemical features. The conjugates of nanoparticles and medicinal plants, or their components known as nano phytomedicine, have been gaining significance lately in the development of novel neuro-therapeutics owing to their natural abundance, promising targeted delivery to the brain, and lesser potential to show adverse effects. In the present review, the promising application, and recent trends of combined nanotechnology and phytomedicine for the treatment of neurological disorders (ND) as compared to conventional therapies, have been addressed. Nanotechnology-based efforts performed in bioinformatics for early diagnosis as well as futuristic precision medicine in ND have also been
discussed in the context of computational approach. schematic presentation of nano-informatic (nanotechnology and bioinformatics) in present dementia or neuro-disorder research.

Materials 15 00804 g002
Schematic presentation of nano-informatic (nanotechnology and bioinformatics) in present dementia or neuro-disorder research. Copyright T. Bhattacharya, Simona Cavalu et al.

Equal advancements in neurophysiology and neuropathology exploration would help in the advancement in nanotechnology, which can be used to provide CNS recovery and neuroprotection. Accordingly, for utilization of nanotechnology in neural system science and neurosurgery, key factors that require consideration include: (1) breakthrough discoveries and developments in drug science and material science, which can help in the manufacturing of the described methodologies; (2) development and advancement of sub-atomic science, sensory system-based neurophysiology, and neuropathology; and (3) planning and combination of explicit nano-empowered therapies to the CNS, which exploit the initial two factors. As a result, nanotechnology could provide the solution and can offer breakthrough therapies for the management and treatment of NDs and can also be used to bypass the current problem of available neurological therapies i.e., non-specific targeting and lower efficacy rates of drug therapies. Therefore, taken together, neurosurgeons, nervous system specialists, neuroscientists, and drug researchers and architects, should take part in utilizing the power of nanotechnology for drug delivery. Consistent with the profoundly interdisciplinary nature of this space of exploration, it is additionally significant to note that nano-informatics and nanotechnology can also provide innovative headways and progressions that are related to fundamental and clinical neuroscience. Copyright T. Bhattacharya, Simona Cavalu et al.

Full text at https://www.mdpi.com/1996-1944/15/3/804/htm

Novel Formulation Based on Chitosan-Arabic Gum Nanoparticles Entrapping Propolis Extract: Production, physico-chemical and structural characterization

By Simona Cavalu et al.

UV-Vis spectra of propolis extract and chitosan/Arabic gum
nanoparticles loaded with propolis. Copyright Simona Cavalu et al.
DLS analyses of colloidal chitosan/Arabic gum/propolis
mixture: a) Particle size distribution; b) Zeta potential. Copyright Simona Cavalu et al.
AFM images of chitosan/Arabic gum nanoparticles
entrapping propolis extract; a) 2D view; b) 3D topography; c)
Surface profile. Copyright Simona Cavalu et al.
AFM images of chitosan/Arabic gum nanoparticles
entrapping propolis extract; a) 2D view; b) 3D topography; c)
Surface profile. Copyright Simona Cavalu et al.
ATR FTIR spectra: a) raw propolis and powder chitosan/Arabic gum/propolis nanoparticles; b) powder chitosan and Arabic gum. Copyright Simona Cavalu et al.

Due to the limitation of chitosan in drug delivery systems, because of its hydrophilicity and solubility, chemical modification was performed in our study by combining with a second natural polymer, Arabic gum, in order to
improve the stability of nanoparticles. Copyright Simona Cavalu et al.

Morphological and structural characterization, using AFM, operating in tapping mode, along with the surface profile. Although the lateral dimensions are influenced by the shape of the probe, the height measurements can provide the height of nanoparticles with a high degree of accuracy and precision. However, larger particles are formed due to the aggregation during storage time. Copyright Simona Cavalu et al.

Structural characterization of polymeric powder
nanoparticles entrapping propolis was performed by ATR
FTIR spectroscopy, and compared with recorded spectrum of raw propolis, chitosan powder and Arabic gum as reference. In the same time, the
marker bands of propolis are well preserved in the polymeric mixture, indicating that the bioactive compounds are stable upon the encapsulation procedure. Copyright Simona Cavalu et al.

In this study we succeeded to prepare and characterize natural polymeric nanoparticles based on chitosan/Arabic gum, entrapping propolis extract. The physico-chemical properties of nanoparticles were assessed by UV-visible and FTIR spectroscopy, along with Dynamic Light Scattering, revealing that particle size obtained from highly dispersed mixture was in the range of 50-400 nm, with large Gaussian distribution, the maximum percentage of size distribution being at around 120 nm. In the same time,
an efficient encapsulation procedure was described using glutaraldehyde as cross-linking agent. The morpholological features of nanoparticles were emphasized by AFM microscopy, demonstrating a good correlation between
the results obtained by DLS technique. The FTIR analysis demonstrated that the marker bands of propolis are well preserved in the polymeric mixture, indicating that the bioactive compounds are stable upon the encapsulation
procedure. In our formulation, we consider that a balanced crosslinking toward electrostatic interaction was established. Propolis release from polymeric matrix was monitored in both simulated gastric acid and simulated intestinal fluids, concluding that our proposed formulation
is suitable for controlled release and pharmaceutical applications. Our results may provide a novel drug design, with improved bioavailability, stability and nutritional value of propolis bioactive compounds during processing and storage, with possible applications in food and nutraceutical industries. Copyright Simona Cavalu et al.

Full text at https://revistadechimie.ro/Articles.asp?ID=6836