Regenerative medicine and cosmetics are currently two outstanding fields for drug discovery. Although many pharmaceutical products for regenerative medicine and cosmetics have received approval by official agencies, several challenges are still needed to overcome, especially financial and time issues. As a result, drug repositioning, which is the usage of previously approved drugs for new treatment, stands out as a promising approach to tackle these problems. Recently, increasing scientific evidence is collected to demonstrate the applicability of this novel method in the field of regenerative medicine and cosmetics. Experts in drug development have also taken advantage of novel technologies to discover new candidates for repositioning purposes following computational approach, one of two main approaches of drug repositioning. Therefore, numerous repurposed candidates have obtained approval to enter the market and have witnessed financial success such as minoxidil and fingolimod. The benefits of drug repositioning are undeniable for regenerative medicine and cosmetics. However, some aspects still need to be carefully considered regarding this method including actual effectiveness during clinical trials, patent regulations, data integration and analysis, publicly unavailable databases as well as environmental concerns and more effort are required to overcome these obstacles.

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer, posing a growing clinical challenge. PTC exhibits two age-related peaks, with established risk factors including family history and radiation exposure. Managing even low-risk, localized PTC cases remain complex, with growing interest in active surveillance as an alternative to immediate surgery. This study employed single-cell RNA sequencing (scRNA-Seq) to explore the predictive value of BRAF and RAS mutations in PTC, shedding light on their impact on disease progression and outcomes. The analyses emphasized the significance of BRAF and RAS mutations in tumor advancement, particularly the unique BRAF V600E mutation associated with aggressive features. The methodology involved scRNA-Seq analysis of PTC and normal samples, unveiling distinct cell clusters and indicating upregulated BRAF and RAS genes. Pathway enrichment analysis highlighted altered biological processes and immune-related pathways in PTC. The study consolidated previous research showing the prevalence of BRAF and RAS mutations in PTC, subtypes with distinct molecular profiles, and the impact of TERT promoter mutations on disease severity. In summary, this study unveils the complex interplay of genetic mutations and the cellular microenvironment in PTC through scRNA-Seq. The upregulated BRAF and RAS genes suggest their roles as PTC drivers, and pathway enrichment reveals alterations in immune-related processes. This synthesis of prior research enhances our understanding of PTC\'s molecular foundations, informing better prognosis and personalized treatment approaches. These insights advance the landscape of PTC management and provide directions for further research.

Aim: This study seeks to explore the possibility of using vitamin E to alleviate the symptoms of polycystic ovarian syndrome (PCOS). Methods: Various computational methods were employed, including network pharmacology utilizing a compound-target-pathway approach, Swiss ADME, OSIRIS® property explorer, pkCSM, PASS online web resource and MOLINSPIRATION® software. In addition, in silico analysis of vitamin E was performed with ten receptors. Results & discussion: Our findings highlight the diverse potential of vitamin E in alleviating PCOS. The observed influence on hormones is in line with existing PCOS theories regarding cyst development, further enhancing the therapeutic promise of vitamin E. Conclusion: In conclusion, our computational analysis indicates that vitamin E shows potential as a therapeutic agent for alleviating PCOS in adolescents.
Polycystic ovarian syndrome (PCOS) is a common condition that affects many girls and young women during their reproductive years. PCOS can lead to problems with the menstrual cycle, difficulties with blood sugar control and sometimes infertility. Unfortunately, there\'s no specific treatment for PCOS yet. This study looked at whether vitamin E might be helpful in treating PCOS in young women. To find out, the researchers used advanced computer-based techniques and analyzed how vitamin E interacts with various parts of the body, including proteins and hormones. Vitamin E appears to influence hormones that play a role in PCOS and cyst formation. It may also have anti-inflammatory properties that could help reduce the symptoms of PCOS. In short, this study suggests that vitamin E might be a valuable option for treating PCOS in adolescents. However, further research and clinical trials are needed to confirm these findings before it can become a standard treatment. This research opens up new possibilities for finding effective solutions for PCOS, which can greatly improve the quality of life for many young women.

UNASSIGNED: Overweight and obesity, high blood pressure, hyperglycemia, hyperlipidemia, and insulin resistance (IR) are strongly associated with non-communicable diseases (NCDs), including type 2 diabetes, cardiovascular disease, stroke, and cancer. Different surrogate indices of IR are derived and validated with the euglycemic-hyperinsulinemic clamp (EHC) test. Thus, using a computational approach to predict IR with Matsuda index as reference, this study aimed to determine the optimal cutoff value and diagnosis accuracy for surrogate indices in non-diabetic young adult men.
UNASSIGNED: A cross-sectional descriptive study was carried out with 93 young men (ages 18-31). Serum levels of glucose and insulin were analyzed in the fasting state and during an oral glucose tolerance test (OGTT). Additionally, clinical, biochemical, hormonal, and anthropometric characteristics and body composition (DEXA) were determined. The computational approach to evaluate the IR diagnostic accuracy and cutoff value using difference parameters was examined, as well as other statistical tools to make the output robust.
UNASSIGNED: The highest sensitivity and specificity at the optimal cutoff value, respectively, were established for the Homeostasis model assessment of insulin resistance index (HOMA-IR) (0.91; 0.98; 3.40), the Quantitative insulin sensitivity check index (QUICKI) (0.98; 0.96; 0.33), the triglyceride-glucose (TyG)-waist circumference index (TyG-WC) (1.00; 1.00; 427.77), the TyG-body mass index (TyG-BMI) (1.00; 1.00; 132.44), TyG-waist-to-height ratio (TyG-WHtR) (0.98; 1.00; 2.48), waist-to-height ratio (WHtR) (1.00; 1.00; 0.53), waist circumference (WC) (1.00; 1.00; 92.63), body mass index (BMI) (1.00; 1.00; 28.69), total body fat percentage (TFM) (%) (1.00; 1.00; 31.07), android fat (AF) (%) (1.00; 0.98; 40.33), lipid accumulation product (LAP) (0.84; 1.00; 45.49), leptin (0.91; 1.00; 16.08), leptin/adiponectin ratio (LAR) (0.84; 1.00; 1.17), and fasting insulin (0.91; 0.98; 16.01).
UNASSIGNED: The computational approach was used to determine the diagnosis accuracy and the optimal cutoff value for IR to be used in preventive healthcare.

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UNASSIGNED: Gene identification for genetic diseases is critical for the development of new diagnostic approaches and personalized treatment options. Prioritization of gene translation is an important consideration in the molecular biology field, allowing researchers to focus on the most promising candidates for further investigation.
UNASSIGNED: In this paper, we discussed different approaches to prioritize genes for translation, including the use of computational tools and machine learning algorithms, as well as experimental techniques such as knockdown and overexpression studies. We also explored the potential biases and limitations of these approaches and proposed strategies to improve the accuracy and reliability of gene prioritization methods. Although numerous computational methods have been developed for this purpose, there is a need for computational methods that incorporate tissue-specific information to enable more accurate prioritization of candidate genes. Such methods should provide tissue-specific predictions, insights into underlying disease mechanisms, and more accurate prioritization of genes.
UNASSIGNED: Using advanced computational tools and machine learning algorithms to prioritize genes, we can identify potential targets for therapeutic intervention of complex diseases. This represents an up-and-coming method for drug development and personalized medicine.

Diabetic retinopathy (DR) is a debilitating diabetic disorder of the retinal microvasculature and the main cause of avoidable blindness in old people. Hesperetin is a plant flavanone largely abundant in citrus species with neuroprotective properties in animal models. This study aimed to explore the neuroprotective and autophagy-enhancing effect of hesperetin in rats with DR. Twenty-four male rats were utilized and allocated to groups: (i) the vehicle group, (ii) DR group and (iii-iv) the DR + hesperetin (50 and 100 mg/kg) groups. Treatment with hesperetin continued for 6 weeks. After the rats were euthanized, their eyes were dissected to detect the biochemical and histological changes in the retinas. Quantification of autophagy markers, beclin 1/LC3/p62, and inflammation markers was performed. Histopathologic changes were investigated after staining with hematoxylin and eosin and periodic acid-Schiff (PAS). Results demonstrated that hesperetin decreased the PAS staining in diabetic rats and attenuated histopathological changes and restored retinal organization and thickness of layers in hematoxylin and eosin staining. Moreover, hesperetin reduced the level of mRNA expression for TNF-α (4.9-fold), IL-1β (4.15-fold), IL-6 (4.6-fold) and NFκB (5.2-fold), as well as the protein level. This was accompanied by induction of autophagy proteins, beclin 1 and LC3-II. Our results afford evidence that hesperetin is effective in alleviating the pathology of DR via suppressing the inflammatory burden and induction of autophagy. After extensive clinical examinations, hesperetin may prove to be a useful option for treatment of DR.

Alzheimer\'s Disease (AD) is a special class of neurodegenerative diseases demarcated as a progressive disorder affecting especially older adults globally. The AD-infected brain shows declination in cognitive functions, memory loss, and other exhausting symptoms. In this study, we focused on using advanced bioinformatics and next-generation sequencing to explore essential clusters of genes from various diversified Alzheimer\'s, Parkinson and Frontotemporal Dementia diseased cases. The significant differential expression analysis of genes (p-value ≤ 0.05, log fold change ≤ 0.05) was carried out, followed by meta-analysis, which resulted in the identification of 20 conserved genes across variable case studies. Out of 20 conserved genes, CASP8 and PTPN11 were observed to show essential regulatory mechanisms in AD metabolic pathways and proceeded further for docking analysis. Moreover, the natural compounds were screened for ligand library preparation based on extensive scientific literature and (ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity)) property check. Molecular docking was carried out with screened ligands and target receptors, resulting in the identification of Rosmarinic acid (RA) with CASP8 having docked score (∆G = -8.0 kcal/mol); Donepezil (FDA drug) dock score (∆G = -7.3 kcal/mol) (control). PTPN11 receptor with Carnosol ligand resulted in docking score (∆G = -9.1 kcal/mol) w.r.t Tacrine (FDA drug) docked score (∆G = -8.0 kcal/mol) followed by MD simulation. This research will aid in the identification of potential natural compounds that future researchers can use for further validation as a potential candidate drug in combating various neurodegenerative diseases highlighting AD.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a causative agent for multiple drug-resistant diseases and is a prime health concern. Currently, antibiotics like vancomycin, daptomycin, fluoroquinolones, linezolid, fifth-generation cephalosporin and others are available in the market for the treatment of MRSA infection.
METHODS: With the increasing prevalence of drug-resistant cases, researchers are actively investigating alternative strategies to combat MRSA, including the exploration of peptide therapeutics. This study employed computational methods to prospect for potential Antimicrobial Peptides (AMPs).
RESULTS: A total of One hundred and fifty antimicrobial peptides were explored based on physicochemical properties. The results showed that Clavanin B was the most appropriate candidate. Molecular Docking and Molecular Dynamics Simulation results showed the protein-peptide interaction of the MRSA target proteins, Penicillin Binding Protein 2a and Panton-Valentine Leukocidin Toxin, with the Antimicrobial Peptide Clavanin B.
CONCLUSIONS: Currently, the antimicrobial peptide database highlights Clavanin B\'s role as an anti-HIV peptide. Moreover, this investigation proposes Clavanin B as a viable repurposed drug for treating MRSA, underscoring its potential deployment in the management of MRSA infections.

After the emergence of the COVID-19 pandemic in late 2019, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has undergone a dynamic evolution driven by the acquisition of genetic modifications, resulting in several variants that are further classified as variants of interest (VOIs), variants under monitoring (VUM) and variants of concern (VOC) by World Health Organization (WHO). Currently, there are five SARS-CoV-2 VOCs (Alpha, Beta, Delta, Gamma and Omicron), two VOIs (Lambda and Mu) and several other VOIs that have been reported globally. In this study, we report a natural compound, Curcumin, as the potential inhibitor to the interactions between receptor binding domain (RBD(S1)) and human angiotensin-converting enzyme 2 (hACE2) domains and showcased its inhibitory potential for the Delta and Omicron variants through a computational approach by implementing state of the art methods. The study for the first time revealed a higher efficiency of Curcumin, especially for hindering the interaction between RBD(S1) and hACE-2 domains of Delta and Omicron variants as compared to other lead compounds. We investigated that the mutations in the RBD(S1) of VOC especially Delta and Omicron variants affect its structure compared to that of the wild type and other variants and therefore altered its binding to the hACE2 receptor. Molecular docking and molecular dynamics (MD) simulation analyses substantially supported the findings in terms of the stability of the docked complexes. This study offers compelling evidence, warranting a more in-depth exploration into the impact of these alterations on the binding of identified drug molecules with the Spike protein. Further investigation into their potential therapeutic effects in vivo is highly recommended.Communicated by Ramaswamy H. Sarma.