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1.
Front Cell Neurosci ; 18: 1399742, 2024.
Article in English | MEDLINE | ID: mdl-39049823

ABSTRACT

Huntington's disease (HD) is caused by an expansion of CAG trinucleotide repeat in the HTT gene; the exact pathogenesis of HD currently remains unclear. One of the promising directions in the study of HDs is to determine the molecular mechanism underlying the development and role of microRNAs (miRNAs). This study aimed to identify the profile of miRNAs in an HD human cell line model as diagnostic biomarkers for HD. To study HD, the human SH-SY5Y HD cell model is based on the expression of two different forms: pEGFP-Q23 and pEGFP-Q74 of HTT. The expression of Htt protein was confirmed using aggregation assays combined with immunofluorescence and Western blotting methods. miRNA levels were measured in SH-SY5Y neuronal cell model samples stably expressing Q23 and Q74 using the extraction-free HTG EdgeSeq protocol. A total of 2083 miRNAs were detected, and 354 (top 18 miRNAs) miRNAs were significantly differentially expressed (DE) (p < 0.05) in Q23 and Q74 cell lines. A majority of the miRNAs were downregulated in the HD cell model. Moreover, we revealed that six DE miRNAs target seven genes (ATN1, GEMIN4, EFNA5, CSMD2, CREBBP, ATXN1, and B3GNT) that play important roles in neurodegenerative disorders and showed significant expression differences in mutant Htt (Q74) when compared to wild-type Htt (Q23) using RT-qPCR (p < 0.05 and 0.01). We demonstrated the most important DE miRNA-mRNA profiles, interaction binding sites, and their related pathways in HD using experimental and bioinformatics methods. This will allow the development of novel diagnostic strategies and provide alternative therapeutic routes for treating HD.

2.
Cytokine ; 182: 156699, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39033730

ABSTRACT

Psoriasis, a prevalent inflammatory skin condition impacting millions globally, continues to pose treatment challenges, despite the availability of multiple therapies. This underscores the demand for innovative treatments. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option due to their capacity to modulate the immune system and facilitate tissue healing. Recent research indicates that MSCs don't just work through direct cell-to-cell interactions but also release extracellular vesicles (EVs), containing various bioactive substances like proteins, lipids, and nucleic acids. This article explores our current knowledge of psoriasis's origins and the potential utilization of MSCs and their EVs, particularly exosomes, in managing the condition. Additionally, we delve into how MSCs and EVs function in therapy, including their roles in regulating immune responses and promoting tissue repair. Lastly, we discuss the obstacles and opportunities associated with translating MSC-based treatments for psoriasis into clinical practice.

3.
Article in English | MEDLINE | ID: mdl-39039685

ABSTRACT

As the world recovers from the COVID-19 pandemic, a resurgence in MPXV cases is causing serious concern. The early clinical similarity of MPXV to common ailments like the flu and cold, coupled with the resemblances of its progressing rash to other infections, underscores the importance of prompt and accurate diagnosis. Among the infections, smallpox is clinically closest to MPXV, and rashes similar to MPXV stages also appear in syphilis and varicella zoster. A comprehensive review of MPXV, herpes, and syphilis was carried out, including structural and morphological features, origins, transmission modes, and computational studies. PubMed literature search on MPXV, using MeSH key terms, yielded 1904 results, with the analysis revealing prominent links to sexually transmitted diseases. More in-depth exploration of MPXV, Herpes Simplex Virus (HSV), and Syphilis revealed further disease interconnections and geographical correlations. These findings emphasize the need for a holistic understanding of these interconnected infectious agents for better control and management.

4.
Pathol Res Pract ; 260: 155422, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38981347

ABSTRACT

Mesenchymal stem/stromal cells (MSCs) are acknowledged for their remarkable ability to undergo differentiation into various cell types. In addition, they exhibit anti-tumor characteristics, prompting endeavors to modify MSCs for employment in cancer therapies. On the contrary, it is imperative to recognize that MSCs have been extensively linked to pathways that facilitate the advancement of tumors. Numerous research studies have sought to modify MSCs for clinical application; however, the outcomes have been ambiguous, potentially due to the heterogeneity of MSC populations. Furthermore, the conflicting roles of MSCs in suppressing and promoting tumor growth present a challenge to the appropriateness of their use in anti-cancer therapies. Currently, there exists a lack of comprehensive comprehension concerning the anti-tumor and pro-tumor characteristics of MSCs for gastric cancer (GC). This article discusses the influence of MSCs on GC, the underlying mechanisms, the origins of MSCs, and their effects. This review article also elucidates how MSCs exhibit dual characteristics of promoting and inhibiting tumor growth. Hence, it is of utmost importance that clinical inquiries aimed at utilizing MSCs as a therapeutic intervention for cancer consider the potentiality of MSCs to accelerate the progression of GC. It is crucial to exercise caution throughout the process of developing MSC-based cellular therapies to enhance their anti-cancer attributes while simultaneously eliminating their tumor-promoting impacts.

5.
Heliyon ; 10(12): e32844, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38975183

ABSTRACT

The most prevalent paediatric vision-threatening medical condition, retinoblastoma (RB), has been a global concern for a long time. Several conventional therapies, such as systemic chemotherapy and focal therapy, have been used for curative purposes; however, the search for tumour eradication with the least impact on surrounding tissues is still ongoing. This review focuses on the genetic origin, classification, conventional treatment modalities, and their combination with nano-scale delivery systems for active tumour targeting. In addition, the review also delves into ongoing clinical trials and patents, as well as emerging therapies such as gene therapy and immunotherapy for the treatment of RB. Understanding the role of genetics in the development of RB has refined its treatment strategy according to the genetic type. New approaches such as nanostructured drug delivery systems, galenic preparations, nutlin-3a, histone deacetylase inhibitors, N-MYC inhibitors, pentoxifylline, immunotherapy, gene therapy, etc. discussed in this review, have the potential to circumvent the limitations of conventional therapies and improve treatment outcomes for RB. In summary, this review highlights the importance and need for novel approaches as alternative therapies that would ultimately displace the shortcomings associated with conventional therapies and reduce the enucleation rate, thereby preserving global vision in the affected paediatric population.

6.
Pak J Med Sci ; 40(5): 962-966, 2024.
Article in English | MEDLINE | ID: mdl-38827843

ABSTRACT

Objective: Evaluation of contemporary disinfection techniques, Moringa Oleifera (M.Oleifera), Phycocyanin activated by photodynamic therapy (PDT), and Chitosan, on S.mutans survival rate and bond integrity of composite to carious-affected dentin (CAD). Methods: The in vitro study was conducted at King Saud University and concluded within three months. Sixty mandibular teeth with cavities extending to the middle third of the dentin were sterilized. S.mutans was inoculated onto the CAD surface of twenty samples. The samples were randomly divided into four groups (n: 15) based on various disinfection regimes. Group-1 received 2% CHX, Group-2 Phycocyanin activated by photodynamic therapy (PDT), Group-3 Chitosan, and Group-4 M.oleifera. S.mutans survival rate was calculated. Ten CAD samples from each group were restored using composite. The bond integrity of samples was assessed using a Universal testing machine (UTM) and failure mode using a stereomicroscope. Analysis of variance (ANOVA) and Tukey's Post Hoc test were used to calculate statistical significance (p=0.05). Results: Group-2 samples subjected to Phycocyanin activated using PDT, displayed minimal survival rate (0.24 ± 0.05 CFU/ml) of S.mutans.Group-1 samples treated with CHX exhibited the highest count of S.mutans (0.69 ± 0.12 CFU/ml). The most robust bond was observed in Group-3 (Chitosan) samples (19.33 ± 0.47 MPa). In contrast, SBS values were lowest in Group-1 (CHX) treated study samples (13.17 ± 1.88 MPa). Conclusion: Chitosan, Phycocyanin activated by PDT, and Moringa Oleifera extract exhibit potential as viable substitutes for chlorhexidine (CHX) in clinical settings, presenting the possibility of better eradication of S.mutans and greater adhesive strength to CAD.

7.
Tissue Cell ; 89: 102415, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38851032

ABSTRACT

Mesenchymal stem cells (MSCs) originating from the umbilical cord (UC) or Wharton's jelly (WJ) have attracted substantial interest due to their potential to augment therapeutic approaches for a wide range of disorders. These cells demonstrate a wide range of capabilities in the process of differentiating into a multitude of cell types. Additionally, they possess a significant capacity for proliferation and are conveniently accessible. Furthermore, they possess a status of being immune-privileged, exhibit minimal tumorigenic characteristics, and raise minimal ethical concerns. Consequently, they are well-suited candidates for tissue regeneration and the treatment of diseases. Additionally, UC-derived MSCs offer a substantial yield compared to other sources. The therapeutic effects of these MSCs are closely associated with the release of nanosized extracellular vesicles (EVs), including exosomes and microvesicles (MVs), containing lipids, microRNAs, and proteins that facilitate intercellular communication. Due to their reduced tumorigenic and immunogenic characteristics, in addition to their convenient manipulability, EVs have arisen as a viable alternative for the management of disorders. The favorable characteristics of UC-MSCs or WJ-MSCs and their EVs have generated significant attention in clinical investigations encompassing diverse pathologies. Therefore, we present a review encompassing current preclinical and clinical investigations, examining the implications of UC-MSCs in diverse diseases, including those affecting bone, cartilage, skin, liver, kidney, neural, lung, cardiovascular, muscle, and retinal tissues, as well as conditions like cancer, diabetes, sepsis, and others.

8.
PLoS One ; 19(6): e0303784, 2024.
Article in English | MEDLINE | ID: mdl-38905286

ABSTRACT

Lung cancer, a relentless and challenging disease, demands unwavering attention in drug design research. Single-target drugs have yielded limited success, unable to effectively address this malignancy's profound heterogeneity and often developed resistance. Consequently, the clarion call for lung cancer drug design echoes louder than ever, and multitargeted drug design emerges as an imperative approach in this landscape, which is done by concurrently targeting multiple proteins and pathways and offering a beacon of hope. This study is focused on the multitargeted drug designing approach by identifying drug candidates against human cyclin-dependent kinase-2, SRC-2 domains of C-ABL, epidermal growth factor and receptor extracellular domains, and insulin-like growth factor-1 receptor kinase. We performed the multitargeted molecular docking studies of Drug Bank compounds using HTVS, SP and XP algorithms and poses filter with MM\GBSA against all proteins and identified DB02504, namely [3-(1-Benzyl-3-Carbamoylmethyl-2-Methyl-1h-Indol-5-Yloxy)-Propyl-]-Phosphonic Acid (3-1-BCMIYPPA) as multitargeted lead with docking and MM\GBSA score range from -8.242 to -6.274 and -28.2 and -44.29 Kcal/mol, respectively. Further, the QikProp-based pharmacokinetic computations and QM-based DFT showed acceptance results against standard values, and interaction fingerprinting reveals that THR, MET, GLY, VAL, LEU, GLU and ASP were among the most interacting residues. The NPT ensemble-based 100ns MD simulation in a neutralised state with an SPC water model has also shown a stable performance and produced deviation and fluctuations <2Å with huge interactions, making it a promising multitargeted drug candidate-however, experimental studies are suggested.


Subject(s)
Lung Neoplasms , Molecular Docking Simulation , Molecular Dynamics Simulation , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/pharmacokinetics , Drug Design , Indoles/chemistry , Indoles/pharmacology , Indoles/pharmacokinetics , Density Functional Theory
9.
Curr Drug Deliv ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38867526

ABSTRACT

INTRODUCTION: Desloratadine, a second-generation antihistaminic drug, is poorly watersoluble and requires amelioration of the dissolution rate to improve its pharmacokinetics properties. METHOD: This study investigated the impact of polymer, surfactant types, and concentration on the particle size, zeta potential, and dissolution efficiency of nanosuspensions formulated through the solvent antisolvent precipitation method. To optimize the delivery of Desloratadine nanosuspension, we used Minitab software and a 4-factor, 2-level full factorial design. Physicochemical properties and drug release studies were conducted to evaluate the suggested nanosuspension formulations. The optimization goals included minimizing particle size and zeta potential while maximizing dissolution efficiencies. RESULT: The selected optimal nanosuspension demonstrated favourable values, including a particle size of 478.63 ± 15.67 nm, a zeta potential of -36.24 ± 3.21 mV, and dissolution efficiencies in double distilled water and buffer of 90.29 ± 3.75 % and 93.70 ± 3.67 %, respectively. The optimized formulation was subjected to additional analysis using X-ray powder diffraction (XPRD), scanning and transmission electron microscopy (SEM and TEM), and Fourier-transform infrared spectroscopy (FTIR). CONCLUSION: The optimized nanosuspension formulation also underwent further studies under optimal lyophilization conditions, revealing the effectiveness of mannitol as a cryoprotectant at a concentration of 8%.

10.
Article in English | MEDLINE | ID: mdl-38818905

ABSTRACT

Central nervous system tumors are abnormal proliferations of neuronal cells within the brain and spinal cord. They can be primary or secondary and place a heavy financial, psychological, and physical burden on individuals. The highly selective blood-brain barrier, which only permits specific molecules to flow into the brain parenchyma, inhibits the efficacy of pharmacological medicines. Treatment options include surgery, chemoradiotherapy, and targeted therapy. Despite advances in therapy over the past few decades, the overall morbidity and mortality rates are still high, emphasizing the need for improved therapeutic choices to improve survival and quality of life further. Nano pharmaceuticals have demonstrated encouraging outcomes in in vivo trials using microscopic particles to enhance bioavailability and selectivity. The most successful clinical results to date have been achieved by liposomes, extracellular vesicles, and biomimetic nanoparticles; nevertheless, clinical trials are required to confirm their safety, efficacy, affordability, longterm impact, and success in patients from various demographics. Nano pharmaceuticals have the potential to change the paradigm of therapy for brain tumors, allowing better outcomes as primary and adjunctive therapy.

11.
Nutr Metab (Lond) ; 21(1): 26, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755627

ABSTRACT

Neurodegenerative diseases represent one of the utmost imperative well-being health issues and apprehensions due to their escalating incidence of mortality. Natural derivatives are more efficacious in various preclinical models of neurodegenerative illnesses. These natural compounds include phytoconstituents in herbs, vegetables, fruits, nuts, and marine and freshwater flora, with remarkable efficacy in mitigating neurodegeneration and enhancing cognitive abilities in preclinical models. According to the latest research, the therapeutic activity of natural substances can be increased by adding phytoconstituents in nanocarriers such as nanoparticles, nanogels, and nanostructured lipid carriers. They can enhance the stability and specificity of the bioactive compounds to a more considerable extent. Nanotechnology can also provide targeting, enhancing their specificity to the respective site of action. In light of these findings, this article discusses the biological and therapeutic potential of natural products and their bioactive derivatives to exert neuroprotective effects and some clinical studies assessing their translational potential to treat neurodegenerative disorders.

12.
EXCLI J ; 23: 300-334, 2024.
Article in English | MEDLINE | ID: mdl-38655092

ABSTRACT

Cutaneous Squamous Cell Carcinoma (cSCC) is a common and potentially fatal type of skin cancer that poses a significant threat to public health and has a high prevalence rate. Exposure to ultraviolet radiation on the skin surface increases the risk of cSCC, especially in those with genetic syndromes like xerodermapigmentosum and epidermolysis bullosa. Therefore, understanding the molecular pathogenesis of cSCC is critical for developing personalized treatment approaches that are effective in cSCC. This article provides a comprehensive overview of current knowledge of cSCC pathogenesis, emphasizing dysregulated signaling pathways and the significance of molecular profiling. Several limitations and challenges associated with conventional therapies, however, are identified, stressing the need for novel therapeutic strategies. The article further discusses molecular targets and therapeutic approaches, i.e., epidermal growth factor receptor inhibitors, hedgehog pathway inhibitors, and PI3K/AKT/mTOR pathway inhibitors, as well as emerging molecular targets and therapeutic agents. The manuscript explores resistance mechanisms to molecularly targeted therapies and proposes methods to overcome them, including combination strategies, rational design, and optimization. The clinical implications and patient outcomes of molecular-targeted treatments are assessed, including response rates and survival outcomes. The management of adverse events and toxicities in molecular-targeted therapies is crucial and requires careful monitoring and control. The paper further discusses future directions for therapeutic advancement and research in this area, as well as the difficulties and constraints associated with conventional therapies.

13.
J Biomol Struct Dyn ; : 1-15, 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38486457

ABSTRACT

The Japanese encephalitis virus, (JEV), is a flavivirus mostly transmitted by Culex mosquitoes mostly present in Southeast Asia and the Western Pacific region. Ardeid-wading birds are the natural reservoir of JEV; nonetheless, pigs are frequently a key amplifying host during epidemics in human populations. Although more domestic animals and wildlife are JEV hosts, it is unclear how these animals fit into the ecology and epidemiology of the virus. Even though there is no specific therapy, vaccines are available to prevent this infection. However, current vaccinations do not work against every clinical isolate and can cause neurological problems in certain people. In this study, we have screened 501 phytochemical compounds from various plants from the Zingeberaceae family against the RdRp protein of JEV. Based on this, the top five compounds (IMPHY014466, IMPHY004928, IMPHY007097, IMPHY014179 and IMPHY005010) were selected based on the obtained docking scores, which was above -8.0 Kcal/mol. Further, the binding affinity of these selected ligands was also analysed using molecular interaction, and the presence of interactions like hydrogen bonds, hydrophobic bonds and polar bonds with respective active residues were identified and studied elaborately. Furthermore, the dynamic stability of the docked RdRp protein with these selected phytochemicals was studied using Molecular dynamic simulation and essential dynamics. The free energy landscape analysis also provided information about the energy transition responsible stability of the complex. The results obtained advocated phytochemical compounds from the zingeberaceae family for future experimental validation, as these compounds exhibited significant potential as JEV antagonists.Communicated by Ramaswamy H. Sarma.

14.
Plants (Basel) ; 13(5)2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38475570

ABSTRACT

Plants that possess a diverse range of bioactive compounds are essential for maintaining human health and survival. The diversity of bioactive compounds with distinct therapeutic potential contributes to their role in health systems, in addition to their function as a source of nutrients. Studies on the genetic makeup and composition of bioactive compounds have revealed them to be rich in steroidal alkaloids, saponins, terpenes, flavonoids, and phenolics. The Solanaceae family, having a rich abundance of bioactive compounds with varying degrees of pharmacological activities, holds significant promise in the management of different diseases. Investigation into Solanum species has revealed them to exhibit a wide range of pharmacological properties, including antioxidant, hepatoprotective, cardioprotective, nephroprotective, anti-inflammatory, and anti-ulcerogenic effects. Phytochemical analysis of isolated compounds such as diosgenin, solamargine, solanine, apigenin, and lupeol has shown them to be cytotoxic in different cancer cell lines, including liver cancer (HepG2, Hep3B, SMMC-772), lung cancer (A549, H441, H520), human breast cancer (HBL-100), and prostate cancer (PC3). Since analysis of their phytochemical constituents has shown them to have a notable effect on several signaling pathways, a great deal of attention has been paid to identifying the biological targets and cellular mechanisms involved therein. Considering the promising aspects of bioactive constituents of different Solanum members, the main emphasis was on finding and reporting notable cultivars, their phytochemical contents, and their pharmacological properties. This review offers mechanistic insights into the bioactive ingredients intended to treat different ailments with the least harmful effects for potential applications in the advancement of medical research.

15.
PLoS One ; 19(3): e0297138, 2024.
Article in English | MEDLINE | ID: mdl-38483874

ABSTRACT

Vitamin D receptor (VDR) gene is implicated in hypertension vulnerability due to its role in regulating the renin-angiotensin system (RAS) and blood pressure. In this case-control study, a carefully selected cohort of 111 hypertensive individuals and 100 healthy controls underwent serum analysis using HPLC to measure 25-hydroxy vitamin D levels. Polymorphic variations in the VDR gene were detected and characterized using the PCR-RFLP method. At first, lower 25-hydroxy vitamin D levels were observed in hypertensive individuals compared to controls (p<0.001). The genotype frequency of the VDR gene TaqI showed no significant difference between cases and controls (p>0.05). Similarly, no significant difference was found in the VDR gene BsmI genotype frequency between hypertensive patients and controls (p>0.05). However, a statistically significant distinction was observed in the VDR gene FokI genotype frequency between cases and controls (p<0.01). The odds ratios for FokI genotypes (CC, CT, TT, and CT+TT) were 1.0, 0.590, 1.566, and 0.963, respectively. Furthermore, serum 25-hydroxy vitamin D levels were significantly higher in control subjects compared to hypertensive patients across all genotypes of VDR (p<0.001). Hypertensive patients, excluding those with the FokI VDR gene CC genotype, exhibited significantly higher systolic blood pressure levels compared to the control group (p<0.05). Similarly, hypertensive subjects displayed elevated diastolic blood pressure levels compared to the control group (p<0.001). Overall, the results suggest the presence of a potential inverse correlation between serum 25-hydroxy vitamin D levels and hypertension. The association analysis conducted indicated that there is no significant association between TaqI and bsmI genotypic variants and the risk of developing hypertension. However, it was observed that VDR gene polymorphisms do have a clear association with hypertension susceptibility, as evidenced by the significantly higher occurrence of FokI genotypic variants in hypertensive patients. Our study therefore introduces the possibility of utilizing 25-hydroxy vitamin D deficiency and VDR gene polymorphisms as a biomarker for hypertension.


Subject(s)
Hypertension , Vitamin D Deficiency , Humans , Receptors, Calcitriol/genetics , Case-Control Studies , Genetic Predisposition to Disease , Polymorphism, Genetic , Vitamin D , Vitamin D Deficiency/complications , Vitamin D Deficiency/genetics , Genotype , Hypertension/genetics , Polymorphism, Single Nucleotide
16.
Arch Gynecol Obstet ; 309(5): 1707-1723, 2024 May.
Article in English | MEDLINE | ID: mdl-38316651

ABSTRACT

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects a substantial percentage of women, estimated at around 9-21%. This condition can lead to anovulatory infertility in women of childbearing age and is often accompanied by various metabolic disturbances, including hyperandrogenism, insulin resistance, obesity, type-2 diabetes, and elevated cholesterol levels. The development of PCOS is influenced by a combination of epigenetic alterations, genetic mutations, and changes in the expression of non-coding RNAs, particularly microRNAs (miRNAs). MicroRNAs, commonly referred to as non-coding RNAs, are approximately 22 nucleotides in length and primarily function in post-transcriptional gene regulation, facilitating mRNA degradation and repressing translation. Their dynamic expression in different cells and tissues contributes to the regulation of various biological and cellular pathways. As a result, they have become pivotal biomarkers for various diseases, including PCOS, demonstrating intricate associations with diverse health conditions. The aberrant expression of miRNAs has been detected in the serum of women with PCOS, with overexpression and dysregulation of these miRNAs playing a central role in the atypical expression of endocrine hormones linked to PCOS. This review takes a comprehensive approach to explore the upregulation and downregulation of various miRNAs present in ovarian follicular cells, granulosa cells, and theca cells of women diagnosed with PCOS. Furthermore, it discusses the potential for a theragnostic approach using miRNAs to better understand and manage PCOS.


Subject(s)
Hyperandrogenism , MicroRNAs , Polycystic Ovary Syndrome , Humans , Female , Polycystic Ovary Syndrome/metabolism , MicroRNAs/genetics , Hyperandrogenism/genetics , Obesity/genetics , Biomarkers
17.
Saudi Pharm J ; 32(3): 101984, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38384476

ABSTRACT

Current research focuses on explicitly developing and evaluating nanostructured lipidic carriers (NLCs) for the chemotherapeutic drug Ribociclib (RCB) via the topical route to surmount the inherent bioavailability shortcomings. The absolute oral bioavailability has not been determined, but using a physiologically based pharmacokinetic model it was predicted that 65.8 % of the standard dose of RCB (600 mg) would be absorbed mainly in the small intestine. RCB-NLCs were produced using the solvent evaporation method, and Box-Behnken Design (BBD) was employed to optimize composition. The prepared NLCs had an average PS of 79.29 ± 3.53 nm, PDI of 0.242 ± 0.021, and a %EE of 86.07 ± 3.14. The TEM analysis disclosed the spherical form and non-aggregative nature of the NLCs. The outcomes of an in-vitro release investigation presented cumulative drug release of 84.97 ± 3.37 % in 24 h, significantly higher than that from the RCB suspension (RCB-SUS). Ex-vivo skin permeation investigations on rodent (Swiss albino mice) revealed that RCB-NLCs have 1.91 times increases in skin permeability comparable to RCB-SUS. Compared to RCB-SUS, RCB-NLCs were able to penetrate deeper into the epidermis membrane than RCB-SUS as per the findings of confocal microscopy. In dermatokinetic study, higher amount of RCB was maintained in both the layers of mice's skin when treated with RCB-NLCs gel comparable to the RCB-SUS gel preparation. The in-vitro, ex-vivo, CLSM, and dermatokinetics data demonstrated a significant possibility for this novel RCB formulation to be effective against skin cancer.

18.
Sci Rep ; 14(1): 3502, 2024 02 12.
Article in English | MEDLINE | ID: mdl-38346990

ABSTRACT

Depression negatively impacts mood, behavior, and mental and physical health. It is the third leading cause of suicides worldwide and leads to decreased quality of life. We examined 18 genes available at the genetic testing registry (GTR) from the National Center for Biotechnological Information to investigate molecular patterns present in depression-associated genes. Different genotypes and differential expression of the genes are responsible for ensuing depression. The present study, investigated codon pattern analysis, which might play imperative roles in modulating gene expression of depression-associated genes. Of the 18 genes, seven and two genes tended to up- and down-regulate, respectively, and, for the remaining genes, different genotypes, an outcome of SNPs were responsible alone or in combination with differential expression for different conditions associated with depression. Codon context analysis revealed the abundance of identical GTG-GTG and CTG-CTG pairs, and the rarity of methionine-initiated codon pairs. Information based on codon usage, preferred codons, rare, and codon context might be used in constructing a deliverable synthetic construct to correct the gene expression level of the human body, which is altered in the depressive state. Other molecular signatures also revealed the role of evolutionary forces in shaping codon usage.


Subject(s)
Codon Usage , Suicide , Humans , Depression/genetics , Quality of Life , Codon/genetics
19.
Article in English | MEDLINE | ID: mdl-38415490

ABSTRACT

BACKGROUND: A nanoemulsion is a colloidal system of small droplets dispersed in another liquid. It has attracted considerable attention due to its unique properties and various applications. Throughout this review, we provide an overview of nanoemulsions and how they can be applied to various applications such as drug delivery, food applications, and pesticide formulations. OBJECTIVE: This updated review aims to comprehensively overview nanoemulsions and their applications as a versatile platform for drug delivery, food applications, and pesticide formulations. METHODS: Research relevant scientific literature across various databases, including PubMed, Scopus, and Web of Science. Suitable keywords for this purpose include "nanoemulsion," "drug delivery," and "food applications." Ensure the search criteria include recent publications to ensure current knowledge is included. RESULTS: Several benefits have been demonstrated in the delivery of drugs using nanoemulsions, including improved solubility, increased bioavailability, and controlled delivery. Nanoemulsions have improved some bioactive compounds in food applications, including vitamins and antioxidants. At the same time, pesticide formulations based on nanoemulsions have also improved solubility, shelf life, and effectiveness. CONCLUSION: The versatility of nanoemulsions makes them ideal for drug delivery, food, and pesticide formulation applications. These products are highly soluble, bioavailable, and targeted, providing significant advantages. More research and development are required to implement nanoemulsion-based products on a commercial scale.

20.
Curr Med Chem ; 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38369709

ABSTRACT

Epidemiological trends in cancer research show that lung cancer can affect up to 1 in 15 men and 1 in 17 women. With incidence rates as high as these and significant associated mortality and morbidity, it is no wonder that lung cancer is one of the main areas of research focused on cancer. Advances in targeted treatments and specialized irradiation protocols have allowed the treatment of more advanced cases. However, as the patient numbers grow, so does the need for cancer-preventive strategies. The present narrative review focuses on soy isoflavones' role in the chemoprevention of lung cancer and their possible role in therapeutic adjuncts. Laboratory studies on lung cancer cell lines have shown that isoflavones can induce apoptosis, tamper with the expression of proliferative molecular pathways, and even reduce tumor angiogenesis. Additionally, population-level studies have emerged that correlate the consumption of isoflavonoids with reduced risk for the development of lung cancer. Interestingly enough, the literature also contains small-scale studies with evidence of isoflavones being effective chemotherapeutic adjuncts that are currently understudied. Our literature review underlines such findings and provides a call for the enhancement of research regarding naturally occurring dietary products with possible anticarcinogenic effects.

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