Current Pharmaceutical Biotechnology - Online First

Generalized anxiety disorder (GAD) is a prevalent and intricate mental disorder that significantly impairs the quality of life of patients. Currently, the exact etiology of GAD remains incompletely understood. Consequently, the discovery of novel drug targets for GAD is highly important.

We obtained cis-eQTL data of druggable genes from the eQTLGen Consortium as the exposure data and GWAS data of GAD from the FinnGen Database as the outcome. The impact of druggable genes on GAD was simulated through Mendelian randomization analysis. Subsequently, a colocalization analysis was conducted to calculate the probability of shared pathogenic variants between the cis-eQTLs of druggable genes and GAD. To further validate our findings, a summary data-based Mendelian randomization (SMR) analysis was carried out.

Mendelian randomization (MR) analysis identified 24 druggable genes with potential causal relationships, among which genetically predicted increased KDM5A levels were associated with a higher risk of GAD (OR=1.0991, 95% CI: 1.0021–1.2056, P=0.0451), suggesting a potential role of KDM5A gene expression in the pathogenesis of GAD. The GAD and KDM5A genes might share a causal variant. The SMR further verified the accuracy of the KDM5A gene.

MR analysis identified KDM5A as a promising therapeutic target for GAD, with additional potential from genes, like MERTK and PPT1. However, the effectiveness of the relevant drug targets requires further validation.

This study suggested that the KDM5A gene might be a potential therapeutic target for treating GAD, providing a direction for future drug development in GAD patients.

The current pharmaceutical industry has increasingly adopted artificial intelligence (AI), integrating it across the entire industrial chain. While AI improves efficiency and reduces costs, it also faces challenges. This study explores both the technological evolution and contemporary innovation hotspots of AI in pharmacy.

This study adopts a fusion analysis of multi-source data, constructing a bi-dimensional analytical framework based on patented inventions (1990-2024) and research articles (2020-2024) as research objects. The study applies the Latent Dirichlet Allocation (LDA) topic model to analyze the evolution of patent topics and employs CiteSpace to construct keyword knowledge graphs from research articles. By integrating patent and article data to define technical labels, the study identifies research hotspots from the perspective of the pharmaceutical life cycle, enabling cross-validation from both scientific and technical dimensions.

The number of AI-related patents in the pharmaceutical field has grown rapidly over the past five years. Technological topics exhibit a distinct evolutionary trend. Research hotspots span the entire pharmaceutical life cycle, from drug development to clinical delivery. Additionally, potential directions for future technological development have been identified.

Research hotspots in the application of AI in pharmaceuticals include target identification, virtual screening, drug delivery, clinical trials, and pharmacovigilance. Precision medicine and explainable AI (XAI)-driven pharmacy modeling are expected to emerge as key directions for future technological development.

AI has already reshaped the pharmaceutical industry through applications across all stages of the pharmaceutical life cycle. It is poised to attract growing research attention and drive innovative applications in the years ahead.

FLRCC is a rare renal carcinoma subtype caused by FH mutations, categorized into hereditary (germline mutations) and sporadic (somatic mutations) forms. These forms are clinically and pathologically similar, complicating differentiation without genetic testing. The aim of this study is to investigate the clinicopathological and molecular genetic differences between hereditary and sporadic fumarate hydratase (FH)-deficient leiomyomatosis and renal cell carcinoma (FLRCC) to improve diagnostic accuracy and clinical management.

A retrospective analysis of 14 FLRCC patients was conducted(May 2020-August 2023). Immunohistochemistry (FH, 2SC, p16), HE staining, and next-generation sequencing (NGS) of tumor tissues and blood leukocytes were performed.

The 14 patients with FH-deficient leiomyoma were 25-54 years old, with a mean age of 36.21 ± 8.16. 78.5% (11/14) had clinical symptoms and multiple, large-sized fibroids (median maximum volume was 75 mm). Patients with leiomyoma and FH deficiency were divided into hereditary and sporadic FLRCC based on FH gene sequencing. Patients with HLRCC had an earlier onset, and the serum tumor marker CA125 was more significant. Moreover, tumor tissues from patients with hereditary and sporadic FH-deficient LRCC differed in immunohistochemical and HE staining characteristics, including more positive p16 and greater susceptibility to invasion and metastasis in patients with HLRCC, as well as malignant proliferation in patients with sporadic FH-deficient LRCC.

Although limited by sample size, our preliminary findings indicated subtle differences in the age of onset, as well as immunohistochemical and histopathological features of hereditary and sporadic FH-deficient LRCC, facilitating the understanding and clinical diagnosis of FLRCC.

In clinical diagnosis, all information should be fully integrated, and a comprehensive judgment should be made to make a correct pathological diagnosis and provide targeted treatment for patients with an FH gene mutation.

This study investigated the role and potential mechanisms of discoidin domain receptor 1 (DDR1) in colon fibrogenesis.

We employed the DSS-induced chronic colitis and fibrosis model to evaluate the therapeutic potential of DDR1 knockout on colonic fibrosis. In vitro experiments involved generating human normal colonic epithelial cells (HIEC line) with DDR1 overexpression by lentivirus transfection. Human colonic fibroblasts were exposed to conditioned medium (CM) from the stably transfected cells that had been treated with transforming growth factor-beta 1 (TGF-β1). The cells were collected for molecular and biochemical analyses.

Our proteomics analysis of DDR1 indicated significant enrichment of proteins involved in the extracellular matrix and fibrosis. In DSS-treated DDR1-KO mice, attenuation of colonic fibrosis and reduced activation of colonic fibroblasts were observed, contrasting significantly with their counterparts in DSS-treated WT mice. Colonic fibroblasts exhibited a marked increase in α-smooth muscle actin and type I collagen expression when exposed to CM from HIEC cells with DDR1 overexpression. Finally, overexpression of DDR1 markedly elevated the levels of p-PI3K, p-Akt, p-mTOR, p62, and LC3B in HIEC cells, resulting in enhanced secretion of TGF-β1.

DDR1 in HIEC cells attenuates autophagy primarily by activating the PI3K/AKT/ mTOR signaling axis and concurrently increasing the autophagic markers LC3B and p62, thereby inducing paracrine secretion of TGF-β1, which drives the activation and proliferation of colonic fibroblasts and elicits a robust profibrotic response.

Our study suggests that DDR1 may be a potential therapeutic target for colonic fibrosis.

Rabies Virus (RV or RABV) is a neurophilic pathogen predominantly transmitted to humans through bites, scratches, or wounds. Upon entering the central nervous system, the virus can cause severe symptoms, including acute encephalitis and paralysis, ultimately leading to death with an almost 100% mortality rate. Hence, it is essential to develop an effective oral rabies vaccine.

We designed and synthesized three modified 5'-cap mRNA vaccines (RV-01(CAP-01), RV-01(CAP-02) and RV-01(CAP-03)) encoding rabies virus glycoproteins in vitro and evaluated their immunogenicity and protective effect in mice.

The modified 5'-cap vaccine was successfully constructed and could be effectively expressed in HEK293 cells. The antibody detection results revealed the abundance of RABV-G in RV-01(CAP-01), RV-01(CAP-02) and RV-01(CAP-03). ELISPOT assays indicated that these variants promoted the production of immune-related cytokines. Furthermore, the modified 5'-cap vaccines could reduce the rabies viral load of mice and effectively prolong their survival.

The rabies mRNA vaccine had high efficacy and safety in preventing rabies, suggesting the great potential of mRNA as a promising candidate for RABV vaccines. However, the potential causes of the differences in the performance of the three modified 5'-cap rabies mRNA vaccines and the clinical application of 5’-Cap altered rabies mRNA vaccines need to be explored.

Hence, these results demonstrated that the modified 5’-cap mRNA vaccine was effective in inducing immune responses, which might be considered a promising prophylactic strategy for rabies.

Breast cancer is a global health challenge with a high mortality rate of 30% of total cases in a year. Breast cancer presents in 4 main types, namely, TNBC, HER2+, luminal A, and Luminal B. Current treatments, though not without side effects, incur substantial cost, and are rendered ineffective by rising drug resistance. Phytochemicals are being investigated for their beneficial effects on breast cancer. Systematically collecting, organizing, and analyzing this data from available literature could benefit the development of more potent chemopreventive and chemotherapeutic approaches with reduced side effects.

To overcome the challenges posed by diverse naming practices, we adopted a sentiment (subjective) based text-mining approach to systematically extract and analyze data on anti-breast cancer phytochemicals from biomedical literature. This method is based on anchor and associated terms to capture authors’ sentiments regarding the therapeutic potential of these compounds. Subsequently, comprehensive and objective information was extracted and curated for each phytochemical, including target genes, pathways, study type, IC50 values, PMIDs, plant sources, and geographical availability.

PhytoCAT (PhytoChemical Affordable Therapeutics for Breast Cancer) is a comprehensive database of phytochemicals, plant extracts, and essential oils, enriched with links to phytogeographic data and chemical structures. PhytoCAT includes data on 28 essential oils, 470 plant extracts, and 1,649 phytochemical compounds. These compounds were classified into several chemical groups, including alkaloids (167), coumarins (43), flavonoids (290), lignans (47), quinones (43), saponins (27), sesquiterpenoid lactones (40), terpenoids (282), triterpenoid saponins (28), and xanthones (22) groups. Additionally, 505 phytochemicals belong to other subclasses such as esters, glucosides, phenanthrenes, and phenylpropanoids. Further, information on their mechanisms of action is also provided.

Phytochemicals have gained significant attention in recent years because of their potential health benefits, particularly in the prevention and treatment of various diseases, including cancer. Compounds such as curcumin, resveratrol, and epigallocatechin gallate (EGCG) are examples of phytochemicals that have shown promise in preclinical studies. PhytoCAT offers a centralized and searchable database enriched with biological, chemical, and pharmacological details. Its structured presentation allows researchers to identify promising compounds and study patterns in chemical class-specific activity.

PhytoCAT provides an evidence-based platform for researchers and clinicians to explore the potential of phytochemicals in breast cancer management. Although PhytoCAT has an advanced search engine, it lacks analytical tools, which we envisage integrating in the future. future. (https://phytocat.igib.res.in/)

Radiation targets cancer but risks causing infertility by damaging sensitive testes, especially spermatogonia. This study investigates IR-induced testicular damage and assesses PGZ's potential protective role as a ferroptosis inhibitor.

In this study, Seventy-two BALB/c mice were randomly divided into eight groups: a control, PGZ (10, 20, and 30 mg/kg), IR (8 Gy), and IR+ PGZ (in three doses). PGZ was administered for 10 consecutive days, and mice were exposed to IR on the 11^th day of the study. 24 h after RT, the mice's testis tissue was subjected to a series of evaluations to assess oxidative stress and antioxidant parameters, with histopathological analyses conducted one week after IR.

Biochemical analyses revealed that exposure to IR significantly increased ferroptosis markers, while concurrently decreasing intracellular antioxidants GSH. Histological examinations confirmed damage to spermatogenic cells, leading to detachment from the basement membrane and reduced sperm counts. Pre-treatment with PGZ at 30 mg/kg effectively reduced the levels of oxidative stress markers and improved antioxidant levels, demonstrating its potential protective effects against ferroptosis.

The results suggest PGZ can protect against radiation-induced testicular damage by inhibiting ferroptosis and promoting spermatogenesis recovery.

These results indicate that PGZ may act as a protective agent against radiation-induced testicular damage and support the recovery of spermatogenesis following IR exposure. Further research is warranted to explore the molecular mechanisms of PGZ's protective effects.

The research on traditional Chinese medicine (TCM) has experienced the transition from qualitative research to quantitative study. The application of mathematical modeling for data processing and analysis offers a more efficient and precise approach compared to conventional methods, enabling the timely acquisition of key efficacy indicators for preliminary evaluation. Therefore, the concept of mathematical modeling has been proposed to form a systematic theoretical system of TCM and diseases.

The article reviews the application of mathematical models in the research of traditional Chinese medicine in terms of compounding, extraction, optimization, quality evaluation, production, new drug development, pharmacokinetics, pharmacodynamics, and clinical symptom analysis. Relevant Chinese and English literature was obtained from PubMed, Cochrane Library, China Science and Technology Journal Database (VIP), Wanfang Data, CNKI and China Biomedical Literature Database (CBM).

We have found that integrating the concept of mathematical modeling with TCM theory has shortened the cycle of extracting active ingredients in traditional Chinese medicine and the development of new drugs, while also accelerating the realization of maximum clinical efficacy.

However, the comprehensiveness and precision of existing databases remain areas for improvement. In the future, further integration of multi-disciplinary technologies will be essential to advance the convergence of traditional medicine and modern science.

This review explores the application of mathematical models in the study of traditional Chinese medicine. It is evident that mathematical modeling has played a pivotal role in promoting fundamental research and the modernization of TCM.

This study aims to examine the impact of Rukangyin (RKY) and its components, LSQR and QTSS, on various cellular processes and signaling mechanisms in MDA-MB-231 triple-negative breast cancer (TNBC) cells.

Twenty-five Sprague-Dawley (SD) rats were randomly assigned to five groups according to the administered drugs, including the RKY group, LSQR group, QTSS group, fluorouracil group, and blank control group (n=5 in each group). The serum samples from each group were then used as a medicated medium for the culture of the TNBC cell line MDA-MB-231. Cell viability tests, apoptosis detection tests, and migration and invasion tests were used to evaluate the cytotoxicity of treated serum. YAP, TAZ, MST1, and LATS1 protein expression and phosphorylation were examined using conventional western blotting methods.

RKY and its QTSS and LSQR components significantly inhibited cell growth and promoted apoptosis in MDA-MB-231 cells. RKY also significantly blocked cell motility with a comparable effect to that of fluorouracil. All serum groups suppressed YAP and TAZ expressions while increasing p-YAP, p-TAZ, MST1, and LATS1 levels, with RKY showing superior efficacy.

In TNBC cells, RKY appears to enhance the tumor-suppressing signals of the Hippo signaling pathway via MST1, LATS1 activation, while restricting its pro-oncogenic action via YAP and TAZ blockade. However, in vivo and animal model experiments are required to confirm these findings.

RKY-medicated serum effectively inhibits growth, induces apoptosis, and reduces motility in the MDA-MB-231 cell line of breast cancer. This therapeutic potential of RKY on TNBC cells draws attention to the need for more investigations.

Cardiovascular diseases (CVDs) are the leading cause of death globally, often complicated by thromboembolic events. Plasmin, a key enzyme in fibrinolysis, is crucial for managing these conditions. Elevated or reduced plasmin levels can indicate thrombotic risks, making it a valuable diagnostic marker. Recent biotechnological advances have developed diagnostic kits to measure plasmin activity, aiding early detection and intervention. Fungal proteases, particularly from micromycetes, are emerging as promising agents in anticoagulant therapy. This study investigates three Aspergillus species — A. caespitosus, A. jensenii and A. neotritici for their potential to produce novel biomedical components.

The fungi were cultured, and their proteolytic profiles were analyzed. Key findings include the identification of specific proteases with plasmin-like and protein C-activating activities. These enzymes were purified using isoelectric focusing and characterized through SDS-PAGE and zymography.

The study confirmed that A. jensenii, and A. neotritici produce proteases with plasmin-like activity, with A. neotritici showing a single 35 kDa non-specific protease, and A. jensenii exhibiting two proteases (33 kDa and 100 kDa) in the acidic zone and one (110 kDa) in the neutral zone, the latter exhibiting specific chymotrypsin and plasmin-like activity.

Among the studied strains, A. neotritici exhibited the fastest secretion of proteases with plasmin-like activity, making it a promising source of enzymes with potential clinical applications. In contrast, A. caespitosus and A. jensenii displayed more complex protease compositions, featuring multiple active enzymes. Notably, one of the A. jensenii proteases showed pronounced specificity toward chymotrypsin and fibrinolytic substrates, indicating its suitability for the development of targeted therapeutic agents.

These findings suggest the potential of these fungal proteases for developing novel anticoagulant therapies and diagnostic tools.

Breast cancer (BC) represents a malignancy affecting populations globally. Its incidence is on the rise. The ethanolic extract of Cyperus rotundus (EECR) has demonstrated potent anticancer activities against multiple human cancer types, inducing apoptosis in BC cells. Autophagic flux protects HER2+ cancer cells from trastuzumab-induced cytotoxicity, so inhibiting it undermines the resistance phenotype. This study aimed to elucidate the therapeutic potential of EECR in trastuzumab-resistant HER2-positive BC and decipher its underlying mechanisms.

Colony formation assay and Cell Counting Kit-8 (CCK-8) assessed cell viability. Flow cytometry was used for cell cycle analysis and apoptosis detection. Western blotting quantified relevant protein expressions. Nude mice were euthanized prior to tissue harvest. Tumor tissues were excised and processed for histological examination, with 5 μm paraffin sections prepared on glass slides for hematoxylin and eosin (H&E) staining. An orthotopic JIMT-1 cell transplantation tumor model was established, and immunohistochemistry was conducted.

EECR demonstrated a dose-dependent suppressive effect on HER2-positive BC cells, inducing apoptosis and G2-M phase cell cycle arrest. It inhibited autophagic flux, as evidenced by LC3 and p62/SQSTM1 accumulation, and upregulated raptor and phosphorylated Mitogen-Activated Protein Kinase (MAPK) in trastuzumab-resistant JIMT-1 cells. Phosphorylated ERK (pERK)/total ERK and Raptor levels were significantly elevated in EECR-treated JIMT-1 cells compared to other treatment groups. Furthermore, EECR significantly inhibited tumorigenic growth in JIMT-1 cells.

This study reveals that EECR effectively impedes autophagic flux in trastuzumab-resistant HER2-positive breast cancer cells, a mechanism increasingly recognized as central to therapeutic resistance. By promoting LC3B and p62 accumulation and modulating the MAPK/mTOR signaling axis, EECR not only disrupts a key survival pathway in resistant cells but also enhances the efficacy of standard chemotherapeutic agents like docetaxel. These dual effects—autophagy inhibition and chemosensitization—underscore EECR’s therapeutic potential as an adjuvant strategy to overcome trastuzumab resistance. Given its multi-target nature and favorable safety profile, EECR represents a promising candidate for future combination therapy in refractory HER2-positive breast cancer.

In view of the increasing resistance of Candida species, it is necessary to explore alternative strategies. In this context, essential oils have emerged as promising options, among which the essential oil of Astronium urundeuva (M. Allemão) Engl. has shown potential, as it is traditionally used in folk medicine for the treatment of inflammation and multiple infections. Thus, the aim of this study was to evaluate the chemical profile, anti-Candida activity, and Fluconazole (FCZ) potentiating effect of the essential oil extracted from the leaves of A. urundeuva (EOAU) and its ability to inhibit the virulence mechanism in Candida species.

The essential oil was obtained via hydrodistillation and characterized using gas chromatography-mass spectrometry. To evaluate the antifungal effects and the modulating activity of Fluconazole (FCZ), the essential oil was diluted in DMSO (1 mL) and SDB medium (9 mL) and tested on 3 Candida strains using the serial microdilution method. In addition, a morphological transition assay was used to evaluate its capacity to inhibit fungal virulence.

The major constituent of EOAU was the monoterpene β-myrcene (71.07%). The results indicate that the essential oil exhibits an antifungal effect, with C. tropicalis being the most susceptible species. At subinhibitory concentrations (MC/8), the EOAU enhanced the action of fluconazole against C. krusei and C. tropicalis. The EOAU strongly inhibited the morphological transition in C. tropicalis.

EOAU is rich in β-myrcene and exhibits an interesting fungistatic effect, making it a great natural candidate for inhibiting Candida spp. virulence.

The crystallization of heme into β-hematin and its subsequent conversion to hemozoin has garnered significant interest as a promising target for the development of novel antimalarial therapies, particularly through the heme detoxification pathway. Furthermore, the therapeutic efficacy of chloroquine (CQ) has been widely recognized, with several studies highlighting its role as an inhibitor of β-hematin and hemozoin formation.

This study reports the synthesis of two novel CQ-derived compounds, 7-chloroquinolin-4-amine (CQC1) and 7-chloro-4-(¹-oxidaneyl)-3,4-dihydroquinoline (CQC2), and evaluates their individual inhibitory effects on β-hematin formation.

Notably, comparative analysis of the experimental data revealed significant variability in the IC50 values for these compounds, which correspond to the concentration required to inhibit 50% of β-hematin synthesis. The impact of incubation time and compound concentration on IC50 values was also investigated.

The findings suggest that increasing the concentration and incubation time of both CQ derivatives led to a reduction in their IC50 values, with both compounds demonstrating enhanced inhibitory activity relative to commercial chloroquine (CQ).

Bacterial cellulose, which is used in many fields from biomedicine to electronics, is promising as an alternative wound dressing instead of traditional gauze in wound treatment.

The objective of this study was to evaluate the potential use of cellulose produced by acetic acid bacteria isolated from rotten fruits as a wound dressing.

In our study, rotten fruit samples were incubated in Hestrin-Schramm (HS) Broth medium. Then, a loopful of the pellicle-forming samples was taken and inoculated onto Hestrin-Schramm (HS) agar using the streak culture method and bacteria were isolated. Identification of bacteria was performed using the BLAST program after 16S rRNA sequence analysis. Physicochemical properties and morphological characterization of bacterial cellulose produced by static culture were examined using Fourier transform infrared (FTIR) and scanning electron microscopy (SEM), respectively, and the swelling ratio was investigated. Antibiotic susceptibilities of bacterial cellulose membranes impregnated with different concentrations of gentamicin (50 µg/mL, 100 µg/mL, 200 µg/mL) against Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 were determined by the disk diffusion method.

The bacteria isolated from rotten fruits were identified as Acetobacter tropicalis NBRC 16470. The structure of cellulose produced by static culture was confirmed by a peak at 3,240 cm⁻¹ in FTIR analysis and fibril structures in SEM analysis. Bacterial cellulose had a swelling ratio of 27.37± 2 .99 fold. The zone diameters formed by bacterial cellulose disk (50 µg/mL gentamicin) and gentamicin (10 µg) disk against Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 were almost the same.

The production of bacterial cellulose, which has the potential to be used as a wound dressing from rotten fruits, is important in terms of recycling and low cost.

The combination of Gardeniae Fructus (ZZ) and Scutellariae Radix (HQ) is a traditional Chinese medicine used for Alzheimer’s disease (AD). However, the molecular mechanisms underlying its anti-dementia effects, particularly its multi-component synergy and pathway modulation, remain poorly understood.

Our study employed an integrated systems pharmacology approach to mechanistically decode the anti-AD properties of ZZ-HQ, combining network pharmacology predictions, molecular docking simulations, and experimental validation to identify critical bioactive components, molecular targets, and therapeutic pathways.

A comprehensive network pharmacology analysis was performed to identify bioactive compounds within the ZZ-HQ complex and their potential protein targets associated with AD. Molecular docking was utilized to predict and assess the binding interactions between key bioactive compounds and AD-related protein targets. Experimental validation focused on baicalin, a major active compound in the ZZ-HQ complex, evaluating its effects on cell viability, apoptosis regulation, oxidative stress reduction, and the activation of the PI3K/Akt signaling pathway.

Fifty-four bioactive compounds were identified in the ZZ-HQ complex, interacting with 258 AD-associated proteins. Key compounds, such as baicalein and norwogonin, demonstrated strong binding affinities with pivotal proteins, including SRC and PIK3R1. Experimental studies further confirmed that baicalin significantly improved cell viability by activating the PI3K/Akt pathway, reducing apoptosis, and alleviating oxidative stress.

Our study uncovered the therapeutic potential of the ZZ-HQ combination in addressing AD through multi-target mechanisms, particularly via modulation of the PI3K/Akt pathway and oxidative stress. These findings provide a scientific basis for the pharmacological effects of ZZ-HQ and offer valuable insights for further research on its potential application in AD treatment.

Oropharyngeal candidiasis (OPC), a fungal infection affecting the mouth and throat, imposes a substantial burden on vulnerable populations such as HIV/AIDS patients, cancer treatment recipients, and the elderly. Conventional antifungal medications are encountering increasing resistance and side effects, necessitating the exploration of novel therapeutic approaches.

This review proposes a comprehensive strategy for developing a novel natural product-based antifungal formulation targeting OPC. The approach involves harnessing promising natural compounds with established antifungal properties and employing advanced delivery systems like mucoadhesive microemulsions to improve efficacy and minimize adverse effects. Additionally, the review explores the integration of computational methods to expedite the identification and development of potent antifungal agents.

A comprehensive literature review was conducted using databases such as PubMed, Scopus, and Web of Science. Search terms included combinations of “oropharyngeal candidiasis,” “natural antifungal agents,” “flavonoids,” “mucoadhesive microemulsions,” “computational drug discovery,” and “in vitro/in vivo studies.” Priority was given to studies published within the last ten years.

The review identifies promising natural compounds with antifungal activity against Candida species commonly associated with OPC. Additionally, several studies highlight the potential of computational tools such as molecular docking and in silico ADMET for rapidly identifying natural compounds with potent antifungal activity and favorable pharmacokinetic and safety profiles. A brief overview of in vitro and in vivo experiments is provided, emphasizing their role in validating the safety and efficacy of the proposed natural product-based antifungal formulation. Formulation and analytical aspects are also discussed.

The multidisciplinary approach outlined, incorporating natural products, computational methods, advanced preclinical in vitro and in vivo experiments, and advanced delivery systems, offers promise for the rapid, cost-effective development of safe and effective optimized formulations to address the growing challenge of OPC, particularly in vulnerable populations.

Nephrotoxicity limits the clinical application of digoxin. One area that might be useful is the mechanical knowledge of altered renal function and renal impairment. We hypothesized that co-administration of naringin would affect digoxin nephrotoxicity by alleviating the altered renal oxidative/ antioxidant redox and apoptotic cascade.

40 male Wistar Albino rats (200 ± 50 g) were grouped into 4, every group included (n= 7), control, Nar., Dig. and Nar. + dig. Groups. Colorimetric estimation of kidney functions and renal oxidative/ antioxidant redox were done.

Comparing digoxin alone, the concomitant administration of digoxin and naringin restored renal antioxidant/ oxidative redox, redistributed Nrf2, HO-1 mRNA exposure with a concomitant down-regulation of NF-κB, AKT and PI3K mRNA expressions. Moreover, a significant decrease of Smad3 and transforming growth factor-β (TGF- β) protein concentrations with a simultaneous rise of Smad7 were noticed in Nar. + dig. Arm when compared to Dig. group.

The co-administration of naringin and digoxin can mitigate digoxin-mediated nephrotoxicity by introducing antioxidant action. This is done by maintaining effects on renal oxidative/antioxidant cycle and lethality via regulating AKT/ PI3k/ Smad3/ Smad7 signaling pathways.

Through comprehensive transcriptome sequencing of liver RNA in mice induced with streptozotocin (STZ) to develop hyperglycemia, we uncovered crucial genes associated with hyperglycemic processes, shedding light on their respective functions. Furthermore, we delved deeply into a discussion surrounding the mechanism behind plasma glucagon-like peptide 1 (PGLP-1) and its role in inhibiting gluconeogenesis.

Liver tissues from mice induced with STZ to develop hyperglycemia (M group), as well as those treated with PGLP-1 (P11 group) and Exendin-4 (E group), were collected. RNA extraction was performed for comprehensive transcriptome sequencing. Differentially expressed mRNA, microRNA (miRNA), and long-chain non-coding RNA (lncRNA) were identified and subjected to analysis of their respective GO and KEGG pathways. An association network involving mRNA-miRNA-lncRNA was constructed to pinpoint target molecules associated with gluconeogenesis. Furthermore, personalized analysis focused on eight gluconeogenesis-related signal pathways obtained from KEGG.

A total of 289 differentially expressed mRNA (dif-mRNA), 21 differentially expressed miRNA (dif-miRNA), and 463 differentially expressed lncRNA (dif-lncRNA) were screened from the M group and P11 group. 182 dif-mRNA, 239 dif-miRNA, and 384 dif-lncRNA were screened from the M group and E group. A total of 427 dif-mRNA, 261 dif-miRNA, and 525 dif-lncRNA were screened from the E group and the P11 group. Among them, mRNA was enriched to the PI3K-Akt signaling pathway, Type ll diabetes mellitus, the Insulin signaling pathway, and the PPAR signaling pathway, while lncRNA was mainly enriched in PI3K-Akt signaling pathway. Similar to the whole transcriptome sequencing, the results of gluconeogenesis personalized analysis showed that the PI3K-Akt signaling pathway was the key pathway, and Gck and Cyp7a1 were highly expressed after PGLP-1 was administered.

According to our findings, we believe that PGLP-1 is a potential regulator of non-coding RNAs, including miRNAs and lncRNAs. Additionally, it modulates the PI3K-Akt signaling pathway, resulting in the upregulation of GcK and Cyp7a1. In this way, it effectively inhibits gluconeogenesis.