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Background and purpose: The increasing rate of opportunistic infections caused by Candida and other yeasts is becoming a major health concern worldwide. However,systematic data on the epidemiology and the yeast species infections in Malaysia is still limited. In this regard, the present research aimed to identify pathogenic yeasts utilizing an economically practical and easily available molecular technique and evaluate the prevalence of pathogenic yeasts in a Malaysian tertiary care hospital.Materials and Methods: Yeast isolates were collected from Sultan Abdul Halim Hospital, Kedah, Malaysia, from October 2020 to October 2021. Molecular identification of the isolates was performed by one enzyme-based polymerase chain reaction restriction fragment length polymorphism method.Results: Candida albicans was the most prevalent species, accounting for 120 isolates (59%) in total. The most prevalent non albicans Candida species were C. tropicalis (n=33,16%), C. krusei (Pichia kudriavzevii) (n=12, 5.8%), C. glabrata (n=12, 5.8%), and C.parapsilosis (n=6, 3%). Other unusual Candida species were C. guilliermondii (2), C.metapsilosis (2), C. orthopsilosis (1), C. lusitaniae (1), C. rugosa (1), C. haemulonii (1), C. bracarensis (1), and C. dubliniensis (1). Moreover, Talaromyces marneffei (1), Kodamaea ohmeri (1), Cryptococcus neoformans (3), and Cryptococcus laurentii (1) were among the other yeasts identified.Conclusion: The Molecular technique used in this study identified 96% of isolates,including mixed species. According to the findings, the most prevalent species are C. albicans, C. tropicalis, C. krusei, and C. glabrata.

Background and Purpose: Invasive candidiasis is one of the most common systemicmycoses, and studies have shown mixed yeast infections. Malaysia lacks mixed yeastculture data.Materials and Methods: Yeast isolates were collected in Sultan Abdul Halim Hospital,North Malaysia, from October 2020 to October 2021. Chromogenic Candida differentialagar media and PCR-RFLP were used to identify yeast species.Results: A total of 206 yeast isolates were collected from different body sites of patients.The majority of the yeast isolates (n=104) were obtained from the urine. Other isolates were extracted from blood (n=52), vaginal swabs (n=45), ear discharge (n=2), tracheal aspirate (n=2), tissue (n=2), skin (n=1), nail (n=1), sputum (n=1), and cerebrospinal fluid (n=1). In total, 200 yeast samples were identified as single species, and six isolates were a mixture of Candida species.Conclusion: Malaysia lacks accurate epidemiological data on mixed yeast infections.We identified all samples to the species level, including mixed yeast cultures, using theMspI enzyme and PCR-RFLP.

Data on the epidemiology and the antifungal susceptibility of Candida species infections in Malaysia is still limited. The study aimed to review and compare studies reporting the prevalence of Candida species and antifungal susceptibility of Candida infections in Peninsular Malaysia. Data from 22 studies published between 2009 and 2018. Data was collected using National Center for Biotechnology Information and Google Scholar using the keywords “Candida and Malaysia.” Around 19 Candida species were identified in a total of 35,608 Candida isolates analyzed in these studies. In most studies examined, C. albicans (66.3%) was the predominant species, followed by C. glabrata (11.7%), C. parapsilosis (10.7%), C. tropicalis (9.5%), and C. krusei (1.19%). Vaginal swabs yielded the most isolates, followed by the respiratory system, urine, blood, oral, pus, and other locations. The demographic, racial, and gender data were recorded only in two studies. Totally, eight studies examined 396 isolates for antifungal susceptibility to common antifungal medications. The average antifungal susceptibility of isolates and efficacy of drugs in these studies ranged between 45 and 99% for most common antifungal drugs. Caspofungin had the highest susceptibility at 99%, whereas itraconazole had the lowest at only 45%. Overall, this review provided a comprehensive summary of all the current research on predominant Candida species in Peninsular Malaysia.

Mushrooms are traditionally used for various medicinal purposes in traditional oriental medicine. The Japanese and Chinese are familiar with the medicinal macro fungus Lentinula edodes (Shiitake mushroom). This study aims to evaluate the role of chemical compounds from L. edodes using network pharmacology and in-vitro studies for management of Obesity. Bioactive compounds in extracts of L. edodes were identified by GC-MS analysis. Compounds were later screened for their drug-like property by Lipinski's rule. In addition, public databases (SEA, STP, Omim and DisGenet) were searched to identify genes associated with selected molecules and obesity, as well as genes that overlap obesity target genes with genes related to L. edodes. Additionally, analysis was performed using Enrichr KG to predict the disease targets of L. edodes. Finally, network was constructed between the overlapping genes and bioactive molecules using Rstudio. Further in-vitro studies were carried out using 3T3-L1 cell line. The genes related to the selected compounds and obesity were identified and overlapped. The disease targets of L. edodes was predicted by enrichment analysis and was found to be linked to obesity. Furthermore, the hub gene was found to be fatty acid amide hydrolase, and the key bioactive compound was hexadecanoic acid methyl ester. The in-vitro cell culture studies confirmed the inhibition of adipogenesis in mushroom extract-treated 3T3-L1 cells and the augmentation of adiponectin. The study suggests that the hub gene fatty acid amide hydrolase might alleviate obesity by inhibiting arachidonoyl ethanolamide signaling, which would enhance the action of fatty acid amide hydrolase and limit appetite in L. edodes extract.

PD-1 (Programmed Cell Death Protein-1) and PD-L1 (Programmed Cell Death Ligand-1) play a crucial role in regulating the immune system and preventing autoimmunity. Cancer cells can manipulate this system, allowing them to escape immune detection and promote tumor growth. Therapies targeting the PD-1/PD-L1 pathway have transformed cancer treatment and have demonstrated significant effectiveness against various cancer types. This study delves into the structure and signaling dynamics of PD-1 and its ligands PD-L1/PD-L2, the diverse PD-1/PD-L1 inhibitors and their efficacy, and the resistance observed in some patients. Furthermore, this study explored the challenges associated with the PD-1/PD-L1 inhibitor treatment approach. Recent advancements in the combination of immunotherapy with chemotherapy, radiation, and surgical procedures to enhance patient outcomes have also been highlighted. Overall, this study offers an in-depth overview of the significance of PD-1/PD-L1 in cancer immunotherapy and its future implications in oncology.

In the present study, we addressed the imperative for potent anticancer agents through Wedelia chinensis, a medicinal plant abundant in the robust antihepatotoxic and antitumor compound wedelolactone. Hindrances in conventional propagation methods due to cross-pollination and habitat degradation prompted us to pioneer in vitro rapid multiplication using plant tissue culture. Optimal outcomes were attained employing Murashige and Skoog (MS) medium supplemented with Indole-3-butyric acid (IBA) (0.5 mg/L) and Kinetin (KN) (5.0 mg/L), yielding 97.67% shoot regeneration and 81.67% rooting from nodal explants. Transplanted plantlets exhibited a 92% survival rate. We established a wedelolactone extraction protocol using toluene:ethyl acetate:formic acid (5:4:1) for High-performance thin-layer chromatography (HPTLC) analysis, trailblazing wedelolactone quantification and 2C DNA analysis in W. chinensis via flow cytometry. Experiments under heavy metal stress with CuSO4 unveiled physiological responses, with peak wedelolactone content [193.90 μg/g dry weight (dw)] in vitro at 75 μM CuSO4, surpassing in vivo levels (89.95 μg/g dw) by 116%. By pioneering successful in vitro rapid multiplication and enhanced wedelolactone content, we bridge a critical gap in the conservation and production of this medicinal plant. Our findings not only offer a sustainable means of propagation but also present a viable strategy for elevating the yield of potent bioactive molecules like wedelolactone, holding immense promise for the development of novel therapeutic interventions and addressing the pressing healthcare challenges of our time.

Head and neck cancers are among the deadliest cancers, ranked sixth globally in rates of high mortality and poor patient prognoses. The prevalence of head and neck squamous cell carcinoma (HNSCC) is associated with smoking and excessive alcohol consumption. Despite several advances in diagnostic and interventional methods, the morbidity of subjects with HNSCC has remained unchanged over the last 30 years. Epigenetic alterations, such as DNA hypermethylation, are commonly associated with several cancers, including HNSCC. Thus, epigenetic changes are considered promising therapeutic targets for chemoprevention. Here, we investigated the effect of EGCG on DNA hypermethylation and the growth of HNSCC. First, we assessed the expression levels of global DNA methylation in HNSCC cells (FaDu and SCC-1) and observed enhanced methylation levels compared with normal human bronchial epithelial cells (NHBE). Treatment of EGCG to HNSCC cells significantly inhibited global DNA hypermethylation by up to 70–80% after 6 days. Inhibition of DNA hypermethylation in HNSCC cells was confirmed by the conversion of 5-methylcytosine (5-mc) into 5-hydroxy methylcytosine (5hmC). DNA methyltransferases regulate DNA methylation. Next, we checked the effect of EGCG on the expression levels of DNA methyltransferases (DNMTs) and DNMT activity. Treatment of EGCG to HNSCC cells significantly reduced DNMT activity to 60% in SCC-1 and 80% in FaDu cells. The protein levels of DNMT3a and DNMT3b were downregulated in both cell lines after EGCG treatment. EGCG treatment to HNSCC cells reactivated tumor suppressors and caused decreased cell proliferation. Our in vivo study demonstrated that administration of EGCG (0.5%, w/w) as a supplement within an AIN76A diet resulted in inhibition of tumor growth in FaDu xenografts in nude mice (80%; p < 0.01) compared with non-EGCG-treated controls. The growth inhibitory effect of dietary EGCG on the HNSCC xenograft tumors was associated with the inhibition of DNMTs and reactivation of silenced tumor suppressors. Together, our study provides evidence that EGCG acts as a DNA demethylating agent and can reactivate epigenetically silenced tumor suppressors to inhibit the growth of HNSCC cells.

Previously, we and others have shown that the regular intake of green tea polyphenols (GTPs) reduces ultraviolet B (UVB) radiation-induced skin cancer by targeting multiple signaling pathways, including DNA damage, DNA repair, immunosuppression, and inflammation. Here, we determine the effect of GTPs on UVB-induced epigenetic changes, emphasizing DNA hypermethylation in UV-exposed skin and tumors and their association with miR-29, a key regulator of DNA methyltransferases (DNMTs). Skin cancer was induced in SKH-1 hairless mice following repeated exposures of UVB radiation (180 mJ/cm2, three times/week, 24 weeks) with or without GTPs supplementation (0.2%) in drinking water. Regular intake of GTPs inhibited tumor growth by hindering the cascade of DNA hypermethylation events. GTPs supplementation significantly blocked UVB-induced DNA hypermethylation in the skin (up to 35%; p < 0.0001) and in tumors (up to 50%; p < 0.0001). Experimental results showed that the levels of DNA hypermethylation were higher in GTPs-treated mice than in the control group. The expressions of miR-29a, miR-29b, and miR-29c were markedly decreased in UV-induced skin tumors, and GTPs administration blocked UVB-induced miR-29s depletion. Furthermore, these observations were verified using the in vitro approach in human skin cancer cells (A431) followed by treatment with GTPs or mimics of miR-29c. Increased levels of miR-29 were observed in GTPs-treated A431 cells, resulting in increased TET activity and decreased DNA hypermethylation. In conclusion, UVB-mediated miR-29 depletion promotes DNA hypermethylation and leads to enhanced tumor growth by silencing tumor suppressors. Regular intake of GTPs rescued UVB-induced miR-29 depletion and prevented tumor growth by maintaining reduced DNA hypermethylation and activating tumor suppressors. Our observations suggest that miR-based strategies and regular consumption of GTPs could minimize the risk of UVB-induced skin cancers and contribute to better management of NMSCs.

Dengue is an important public health problem worldwide, with India contributing nearly a third of global dengue disease burden. The measurement of neutralizing antibody responses is critical for understanding dengue pathophysiology, vaccine development and evaluation. Historically, dengue virus neutralization titers were measured using plaque reduction neutralization tests (PRNTs), which were later adapted to focus reduction neutralization tests (FRNTs). Given the slow and laborious nature of both these assays, there has been interest in adapting a high-throughput flow cytometry based neutralization assay. However, flow cytometry based assays typically underestimate neutralization titers, and in situations where the titers are low they can even fail to detect neutralization activity. In this study, by evaluating graded numbers of input Vero cell numbers and viral inoculum, we optimized the flow cytometry based neutralization assay in such a way that it is sensitive and scores titers that are in concordance with focus reduction neutralization tests for each of the four dengue virus serotypes (p < 0.0001). Given that dengue is a global public health concern, and several research groups are making efforts to understand its pathophysiology and accelerate vaccine development and evaluation both in India and worldwide, our findings have timely significance for facilitating these efforts.