Sorafenib is a first-line treatment for patients with advanced hepatocellular carcinoma (HCC), but its clinical efficacy is often compromised by the acquisition of drug resistance. Various cancers, including HCC, are affected by long non-coding RNA (lncRNA), but the mechanisms underlying HCC sorafenib resistance have not been extensively studied. This article aims to summarize the recently reported pathways associated with sorafenib resistance and discusses potential applications for the treatment of HCC. Relevant studies on the resistance of HCC to anti-tumor drugs were retrieved from PubMed. Given the compelling evidence that sorafenib is an effective treatment for advanced HCC, we analyzed the research papers on lncRNA and sorafenib resistance in HCC in the PubMed system in the past decade and found that lncRNA may be involved in sorafenib resistance in HCC through multiple pathways. lncRNA is widely involved in the resistance mechanism of HCC to sorafenib. Recent studies have revealed that numerous lncRNAs, such as NEAT1, affect the sensitivity of HCC to sorafenib through various mechanisms, including autophagy and AKT signaling pathways. lncRNAs play a pivotal role in modulating HCC resistance to sorafenib. And lncRNA is expected to become a new solution to the resistance of sorafenib and other targeted drugs.

The human skin, being the largest organ, provides defense against bacteria, toxins, and ultraviolet radiation. The skin may experience changes like dryness, photodamage, oxidative damage, and inflammation. This review explores sources of fatty acids and how they can prevent skin damage, with the goal of determining their potential for preventing skin aging. The role and significance of various mechanistic pathways and molecular targets involved in skin aging are highlighted. By using current research findings, this review contributes to a comprehensive understanding of how fatty acids may serve as a proactive approach to promoting youthful skin and mitigating the signs of skin aging. In addition to treating specific skin conditions, nutraceuticals offer immense potential to minimize, postpone, or prevent premature skin aging. The substances that are most frequently employed include carotenoids, polyunsaturated fatty acids, plant polyphenols, bioactive peptides, oligosaccharides, and vitamins. Numerous human trials have demonstrated the impact of supplementing with these items on indicators of aging. The most pertinent clinical and non-clinical investigations are assessed in this review. Based on the comprehensive understanding of the significant role of fatty acids in addressing skin aging, this review may open doors and offer avenues for future explorations.

This research explored the antimicrobial, antifungal, and in vivo anticandidal activities of two herbal extracts: Ocimum basilicum (HEOB) and Ocimum sanctum (HEOS). Additionally, the study analyzed the phytochemical components of these extracts. To examine the efficacy of HEOB and HEOS extracts in terms of their antimicrobial, antifungal, and anti-candidal activities and analyze their phytochemical composition, antioxidant potential, and immunomodulatory properties in vivo. Dried flowers and leaves from Ocimum basilicum and Ocimum sanctum were extracted using a cold maceration process with a 1:1 ethanol-water solution. Phytochemical analysis followed established protocols, and the total phenolic and flavonoid contents were measured using colourimetric methods. HPLC was used to determine the concentrations of specific compounds, including rosmarinic acid, rutin, eugenol, and quercetin. Antioxidant activity, specifically nitric oxide (NO) scavenging and antimicrobial properties, was assessed in vitro using the cup plate method. In vivo studies were conducted on immunocompromised mice with systemic candidiasis, treated with plant extracts at 200 and 400 mg/kg or with ketoconazole as a control. Survival rates, tissue histology, and leukocyte counts were evaluated, and statistical analysis was performed using ANOVA. HEOB and HEOS extracts possess strong antimicrobial and antioxidant activities, largely due to flavonoids such as rutin, quercetin, rosmarinic acid and eugenol. In vivo experiments revealed that both extracts effectively reduced fungal load, increased survival rates, and alleviated immunosuppression in mice with systemic candidiasis. The extracts also exhibited significant immunomodulatory properties by boosting cellmediated immune responses. At higher concentrations, the antifungal performance of HEOB and HEOS was similar to that of ketoconazole. HEOB and HEOS exhibited strong antibacterial, antifungal, and anticandidal properties, showing significant effectiveness in treating systemic candidiasis. Their immunomodulatory effects and ability to boost cell-mediated immunity make these extracts promising options for addressing systemic candidiasis, particularly in individuals with weakened immune systems. This research offers valuable insights and sets the stage for future investigations into the treatment of oral and vaginal candidiasis.

Rheumatoid Arthritis (RA) is a chronic autoimmune disease that prominently affects the joints of the body, including one or more types, such as wrists, knees, fingers, and toes. This condition is characterized by specific auto-immune responses, i.e., inflammation, swelling, stiffness, and pain in the body's joints. This results in partial or complete immobility. Several treatment options are available in the pharmaceutical market, commonly immunosuppressants, anti-inflammatory drugs, corticosteroids, anti-antibody drugs, etc. However, such drug treatments provide only symptomatic relief and lack long-term therapeutic efficacy. Thus, there is a need to develop an alternative treatment option that potentially can cure this disease. Recently, researchers have shifted their focus to targeting the root cause involved in the pathogenesis of RA by designing nucleic-acid- based molecules. With this objective, we have provided this review in which we have explored the nucleic acid-based techniques used to treat RA. Various molecular and genetic methods, including antisense oligonucleotides, small interfering RNA (siRNA), CRISPR-Cas9 gene editing, RNA-based vaccines, microRNA (miRNA) therapeutics, and epigenetic modifications are used to target the mechanisms underlying RA pathogenesis. Through the extensive evaluation of clinical and preclinical studies, we reported nucleic acid-based therapy's clinical efficacy, safety, and therapeutic benefits. In addition, this study states the associated pharmacokinetic challenges followed by approaches to overcome them. Nucleic acid-based therapies are susceptible to degradation by nucleases in the body and are not efficiently absorbed due to their considerable molecular weight. Specialized carriers like nanoparticles are employed for their effective delivery. Nucleic acid-based therapies hold immense potential for achieving more effective, less toxic, and patient-centric management of RA, offering hope for improved outcomes and an enhanced quality of life for individuals living with this challenging autoimmune condition.

Datura stramonium (DS) possesses strong medicinal and therapeutic potential but has been rarely evaluated in this context. The present study was intended to evaluate the antioxidant, hepatoprotective, and nephroprotective potential of the crude methanolic leaf extract and ethyl acetate, chloroform, n-hexane, and aqueous fractions of DS in paracetamol-intoxicated rabbits. Paracetamol (2 g/Kg BW) was applied to induce liver and kidney injury in rabbits while the methanolic extract and fractions of DS were applied in the dose range of 150 mg/Kg to 300 mg/Kg body weight for 21 days. Histopathology of the liver, and kidney and analysis of ALT (Alanine Transaminase), ALP (Alkaline Phosphatase), total bilirubin, serum urea, serum creatinine, and serum uric acid were carried out. In vitro antioxidant potential of the extract and fractions of DS was carried out through DPPH (1,1-diphenyl 2-picrylhydrazyl) free radical scavenging assays. The hepatoprotective and nephroprotective potential of the extract and fractions of DS at the dose level of 300 mg/Kg BW was highly significant (P ˂ 0.01). ALT was found elevated in the paracetamol-treated group (117.3 ± 1.61 U/L) compared to the group treated with methanolic extract of DS, (57.3 ± 0.87 U/L) and normal control group (60.6 ± 1.58 U/L) at 300 mg/kg BW. Elevated levels of ALP (120 ± 1.58 U/L) and Bilirubin (1.6 ± 0.32 mg/dl) were found in the paracetamol-treated group compared with the group treated with methanolic extract of DS (67.5 ± 1.35 U/L; 0.2 ± 1.0 mg/dl) and normal control group (70.1 ± 1.53 U/L; 0.4 ± 0.16 mg/dl) respectively at 300 mg/kg BW. The methanolic extract of DS produced a marked scavenging activity of the DPPH free radicals (88.2 ± 0.006 %) followed by the fractions of DS compared to ascorbic acid (95.5 + 0.003%) at a concentration of 1000 μg/ml. The effects were comparable to those produced by ascorbic acid. Liver and kidney histology of the rabbits treated with extract, fractions, and ascorbic acid of DS caused reductions in the pathological features compared to the paracetamol-treated animals. The histological observations and chemical pathological alterations demonstrated the significant hepatoprotective and nephroprotective benefits of the DS extract and its fractions. It has been concluded that the methanolic extract and fractions of DS possess antioxidant, hepatoprotective, and nephroprotective properties in paracetamol-intoxicated rabbits.

Quercetin, a bioactive flavonoid extracted from traditional Chinese medicine, has antihepatocellular carcinoma effects. Farnesoid X receptor (FXR), a nuclear receptor highly expressed in the liver, plays important roles in maintaining hepatic glucose homeostasis, anti-inflammation, liver regeneration, and anti-cancer properties. Whether quercetin regulates the glycolysis/glycolysis pathway through FXR signaling remains unknown. KEGG Enrichment, GO Enrichment, Protein-Protein Interaction (PPI) Network, Molecular Docking, and RNA-Seq Analysis (Swiss Target Prediction, GeneCard databases, Kaplan-Meier Plotter, etc). Cell activity, cell proliferation, and cell cycles were separately analyzed by CCK-8 assay, clone formation assay, and flow cytometry. QRT-PCR determined the mRNA levels of related genes in response to quercetin. HPLCMS/ MSHPLC-MS/MS determined the metabolite profiles. FXR deficiency Hep3B cells were used for discriminating the quercetin's effects with or without FXR. Quercetin-related genes were significantly correlated with FXR in hepatocarcinogenesis, especially in glycolysis. The top 30 related genes between FXR, quercetin, and glycolysis were enriched and chosen to further study. Furthermore, the strongest binding energy determined by the molecular docking model of between quercetin and FXR was -6.55 kcal/mol. Quercetin inhibited cell proliferation by the accumulation of Hep3B cells in the S-phase. The differential expressed genes (C-MYC, PCNA, CYCLIN-D1, and P21) associated with glycolysis were observed. Furthermore, quercetin also inhibited the expression of HK2, GAPDH, and LDHA. Meanwhile, the levels of glycolysis/gluconeogenesis-related metabolites were regulated by quercetin. Quercetin makes an essential anti-HCC effect by crippling the glycolysis/gluconeogenesis process via FXR signaling.

Objective In this study, the causation between serum metabolites and the risk of Diabetic Nephropathy (DN) was investigated by means of a Mendelian Randomization (MR) analysis.Methods Our data on diabetic nephropathy were obtained from the IEU OpenGWAS Project database, while serum metabolite data originated came from the GWAS summary statistics by Chen et al. The Inverse Variance Weighted (IVW) method was the main analysis approach, with Weighted Median (WME) and MR-Egger regression serving as supplementary approaches to construing the causalities between serum metabolites and the DN risk. In addition to the MR-Egger regression intercept, Cochran's Q test was utilized for sensitivity analysis, with P values used as the metric to assess the results.Results In total, 14 SNPs regarding serum metabolites were chosen as Instrumental Variables (IVs). The IVW results indicated that levels of Behenoylcarnitine (C22), Arachidoylcarnitine (C20), and the ratio of 5-methylthioadenosine (MTA) to phosphate exerted a positive causal effect on the DN risk. Conversely, levels of 5-hydroxylysine, Butyrylglycine, 1-stearoyl-glycerophosphocholine (18:0), Isobutyrylglycine, 1-stearoyl-2-oleoyl-GPE (18:0/18:1), N2,N5-diacetylornithine, 2-butenoylglycine, 3-hydroxybutyroylglycine, N-acetyl-isoputreanine, the ratio of Arginine to Ornithine, and the ratio of Aspartate to Mannose exerted a negative impact of causality on the DN risk. By identifying these serum metabolites, high-risk patients can be recognized in the early stages of diabetic nephropathy, enabling preventive measures or delaying its progression. These findings also provide a solid foundation for further research into the underlying etiology of diabetic nephropathy.Conclusion The translation of serum metabolites into clinical applications for DN aims to utilize changes in serum metabolites as biomarkers for early diagnosis, thereby monitoring the progression of DN and providing a foundation for personalized treatment. For instance, the development of serum metabolite diagnostic kits could be used for early detection and prevention of DN. Changes in metabolites can help identify different stages of DN.

Nutraceuticals like methyl gallate and chia seed oil are gaining global attention for their therapeutic potential. This study investigates their effects on hepatocyte apoptosis and liver architecture in a doxorubicin-induced hepatotoxicity model, utilizing techniques such as TUNEL assay, immunohistochemistry (Bax & Bcl2), H&E staining, and scanning electron microscopy. Thirty female Wistar rats were divided into five groups (n=6): Group I (Normal healthy control), Group II (Doxorubicin-intoxicated control), Group III (Doxorubicin-intoxicated + methyl gallate), Group IV (Doxorubicin-intoxicated + chia seed oil), and Group V (Doxorubicin-intoxicated + both). Liver function tests, histology, and cell apoptosis analysis were performed to assess the effects. Doxorubicin-intoxicated rats (Group II) exhibited significantly elevated ALT, AST, and ALP levels (p < 0.001) and severe hepatic damage compared to controls. Group III and Group IV showed significant reductions in liver enzyme levels (p < 0.05 and p < 0.01, respectively), while Group V demonstrated the most significant decrease (p < 0.001). Immunohistochemistry revealed increased Bax and decreased Bcl2 expression in Group II (p < 0.001), which improved significantly with methyl gallate, chia seed oil, and their combination (p < 0.05 to p < 0.001). TUNEL assay showed reduced apoptotic index in treatment groups, with Group V showing the most significant reduction (p < 0.001). Scanning electron microscope (SEM) analysis confirmed restoration of hepatocyte architecture, especially in Group V. Methyl gallate and chia seed oil, individually and in combination, demonstrated significant hepatoprotective effects against doxorubicin-induced hepatotoxicity, with the combination showing the greatest efficacy. These nutraceuticals hold promise as adjunct therapies to reduce doxorubicin-induced liver injury.

Pyrido[2,3-d]pyrimidine and its derivatives have garnered significant attention due to their potential biological and pharmacological activities. Research has demonstrated their significant potential for antitumor and antibacterial applications. Over the years, pyrido[2,3-d]pyrimidine derivatives have remained a research focus for scientists, with numerous synthetic methods and reaction conditions reported. This review comprehensively summarizes the fast, facile, and economical synthetic methods for pyrido[2,3-d]pyrimidine derivatives over the past years, which are categorized based on different synthetic precursors, and evaluates their antitumor and antibacterial activities, aiming to make them better serve the cause of human health.

Chitosan is a kind of natural material with many unique physicochemical and biological properties related to antibacterial, antioxidant, and chelating. In recent years, chitosan-based nano gels (CS-NG) have been widely used in the field of cancer nanomedicine due to their excellent characteristics including biodegradability, biocompatibility, flexibility, large surface area, controllability, high loading capacity, and especially it can be engineered to become stimuli-responsive to tumor environments. In this review, we summarized the main synthesis approaches of CS-NGs including radical polymerization, self-assembly, microemulsion, and ionic gelation methods. These novel CS-NGs are applied in cancer nanomedicine serving as drug delivery, gene delivery, and bioimaging. Besides, we proposed our perspectives regarding the clinical development of CS-NGs cancer nanomedicine applications.