Assessment of heat stress contributing factors in the indoor environment among vulnerable populations in Klang Valley using principal component analysis (PCA).

Rising global temperatures can lead to heat waves, which in turn can pose health risks to the community. However, a notable gap remains in highlighting the primary contributing factors that amplify heat-health risk among vulnerable populations. This study aims to evaluate the precedence of heat stress contributing factors in urban and rural vulnerable populations living in hot and humid tropical regions. A comparative cross-sectional study was conducted, involving 108 respondents from urban and rural areas in Klang Valley, Malaysia, using a face-to-face interview and a validated questionnaire. Data was analyzed using the principal component analysis, categorizing factors into exposure, sensitivity, and adaptive capacity indicators. In urban areas, five principal components (PCs) explained 64.3% of variability, with primary factors being sensitivity (health morbidity, medicine intake, increased age), adaptive capacity (outdoor occupation type, lack of ceiling, longer residency duration), and exposure (lower ceiling height, increased building age). In rural, five PCs explained 71.5% of variability, with primary factors being exposure (lack of ceiling, high thermal conductivity roof material, increased building age, shorter residency duration), sensitivity (health morbidity, medicine intake, increased age), and adaptive capacity (female, non-smoking, higher BMI). The order of heat-health vulnerability indicators was sensitivity > adaptive capacity > exposure for urban areas, and exposure > sensitivity > adaptive capacity for rural areas. This study demonstrated a different pattern of leading contributors to heat stress between urban and rural vulnerable populations.

Association between physiological responses and heat shock protein 70 (HSP70) expressions in the vulnerable populations of Kuala Lumpur.

Continued heat exposure can cause physiological and cellular responses. This study investigated the association between physiological responses and heat shock protein 70 (HSP70) expressions in Kuala Lumpur's urban vulnerable population. We conducted a cross-sectional study involving 54 participants from four areas classified as experiencing moderate to strong heat stress. Physiological measurements included core body temperature, heart rate, and diastolic and systolic blood pressure. RT-qPCR and ELISA were also performed on blood samples to assess HSP70 gene and protein expressions. Despite indoor heat stress, participants maintained normal physiological parameters while there were significant indications of HSP70 expression at both the gene and protein levels. However, our study found no significant correlation (p > 0.05) between physiological responses and HSP70 expressions. This study shows no interaction between physiological responses and HSP70 expressions in the study population, revealing the complex mechanisms of indoor heat stress in vulnerable individuals.

Best practices for managing malodorous and infected wounds in advanced cervical cancer.

This cross-sectional study was conducted to examine the most effective strategies for managing malodorous and infected wounds in patients who have been diagnosed with advanced cervical cancer. The research was conducted in Liupanshui, China. The study specifically examined demographic profiles, wound characteristics and effectiveness of wound management approaches. The study incorporated the heterogeneous sample of 289 participants who fulfilled the inclusion criteria. Data collection was conducted via structured questionnaires and medical record evaluations. Descriptive statistics and statistical analyses, such as regression analysis, were utilized to evaluate demographic attributes, wound profiles and effects of different approaches to wound management. The findings unveiled the heterogeneous demographic composition of patients, encompassing differences in socioeconomic standing, educational attainment and age. A wide range of wound characteristics were observed, as 65.7% of lesions during the acute phase with diameter between 2 and 5 centimetres, while 41.5% of lesions had this range. The most prevalent types of infections were those caused by fungi (48.4%), followed by bacterial infections lacking resistance (38.1%). A moderate degree of odour intensity was prevalent, affecting 45.0% of the cases. With maximal odour reduction of 80%, a mean healing time of 25 days and patient satisfaction rating of 4.5 out of 5, Negative Pressure Wound Therapy demonstrated itself to be the most efficacious treatment method. Additional approaches, such as photodynamic therapy and topical antibiotic therapy, demonstrated significant effectiveness, as evidenced by odour reductions of 70% and 75%, respectively, and patient satisfaction ratings of 4.3 and 4.2. Thus, the study determined challenges associated with management of malodorous and infected lesions among patients with advanced cervical cancer. The results underscored the significance of individualized care approaches, drew attention to efficacious wound management techniques and identified critical determinants that impacted patient recuperation. The findings of this study hold potential for advancing palliative care for individuals diagnosed with advanced cervical cancer.

Effect of Dietary Fiber Supplementation on Metabolic Endotoxemia: A Protocol for Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Introduction: Metabolic endotoxemia (ME) is the main cause of sub-clinical chronic inflammation, which subsequently triggers the onset of several chronic diseases. However, recent reports have indicated that dietary fiber (DF) contributes significantly to ameliorating ME and inflammation. This protocol aims to provide an outline of all procedures in synthesizing the available data on the effect of DF against ME. Methods: Following the PRISMA 2020 guidelines for preparing protocols, this protocol was registered in the International Prospective Registry of Systematic Reviews (PROSPERO) with registration number (CRD42023417833). In this review, we specifically focused on the inclusion of clinical trials that met the following criteria: they were published or available as preprints, employed random, quasi-random, or cross-over designs, and were exclusively documented in the English language. Clinical medical subject headings (MeSH) as search terms were used on prominent databases such as MEDLINE, COCHRANE library, PubMed, World Health Organization International Clinical Trials Registry Platforms, and US National Institutes of Health Ongoing Trials Register Clinicaltrials.gov. Results and discussion: This protocol will guide the exploration of articles that report changes in ME biomarkers in subjects supplemented with DF. The findings of this protocol will ensure a comprehensive evaluation of available evidence, provide a quantitative summary, identify patterns and trends, enhance statistical power, and address heterogeneity, which collectively will clarify the optimal types, doses, and duration of DF interventions for managing ME and low-grade inflammation. Ethics and dissemination: The quantitative data of clinical trials will be collected, and a meta-analysis will be performed using RevMan V.5.3 software. Therefore, no ethical approval is required.

Induction of Apoptosis and Modulation of Caspase Activity on MCF-7 Human Breast Cancer Cells by Bioactive Fractionated Cocoa Leaf Extract.

BACKGROUND: The objective of this study was to investigate the potential anti-proliferative activities of a methanolic extract of cocoa leaves (CL) obtained through sequential partition and fractionation against MCF-7 breast cancer cells.  Methods: The methanolic extract of CL was partitioned in three separated solvents (hexane, dichloromethane, and methanol). Hexane partition was the most potent against MCF-7 cells growth with the lowest IC50 value. Then, it was subjected to two fractionation procedures, resulting in the identification of the CL bioactive fraction (II-F7) with potent toxicity against MCF-7 cells. RESULTS: Further investigation into CL bioactive fraction (II-F7) revealed significant dose-dependent growth inhibitory effects on MCF-7 cells, which were attributed to the induction of apoptosis, as evidenced by the presence of apoptotic bodies, fragmented DNA, and disruption of mitochondrial membrane potential. Additionally, treatment with CL bioactive fraction (II-F7) upregulated the expression of pro-apoptotic genes (DDIT3, GADD45G and HRK) and significantly increased the activities of caspase-8 and caspase-9. CONCLUSION: Overall, this study suggests that bioactive fraction (II-F7) from CL extract has significant and selective cytotoxicity against MCF-7 cells through inducing apoptosis and has potential as a therapeutic agent for breast cancer treatment.

The Efficacy of Metformin and Exenatide in Polycystic Ovary Syndrome (PCOS) Patients / La eficacia de metformina y exenatida en pacientes con síndrome de ovario poliquístico (SOP)

Introducción: El Síndrome del Ovario Poliquístico (SOP) es un trastorno hormonal que afecta al 5-10% de las mujeres que se encuentran en edad reproductiva. este metanálisis tiene como objetivo evaluar la eficacia de la metformina y la exenatida, respectivamente, y comparar la eficacia de ambos fármacos utilizando el Índice de Masa Corporal (IMC), el colesterol de lipoproteínas de baja densidad (LDL-C), el colesterol de lipoproteínas de alta densidad (HDL-C) y los niveles de testosterona. Método: En este estudio se consultaron Scopus, Science Direct, Oxford Journal, Wiley Online Library y Medline a través del motor de búsqueda PubMed. El análisis estadístico de los estudios incluidos se realizó mediante el software RevMan 5.4. Resultados: Hubo 6 estudios incluidos en el análisis del estudio. Hubo una reducción significativa en el IMC de las pacientes con SOP con exenatida frente a metformina (diferencia de medias = 0,51; intervalo de confianza (IC) del 95 % = 0,07; 0,96; I 2 = 52 %; p = 0,02). También hubo una reducción significativa en el nivel de testosterona de los pacientes con SOP con exenatida frente a metformina (diferencia de medias = 0,15; intervalo de confianza (IC) del 95 % = 0,07; 0,22;I 2 = 0 %; p = 0,0002). No hubo efecto sobre la media de LDL-C y de HDL-C cuando se comparó entre metformina y exenatida. Este muestra que la exenatida es eficaz para reducir el IMC y los niveles de testosterona en pacientes con SOP. Conclusiones: Hubo una reducción significativa en el IMC y los niveles de testosterona de los pacientes con SOP cuando se usó exenatida en comparación con metformina. Sin embargo, no hubo efecto sobre la media de los niveles de LDL-C y HDL-C de las pacientes con SOP. (AU)

Introduction: Polycystic Ovary Syndrome (PCOS) is a hormonal disorder that affects 5-10% of women who are their reproductive age. This meta-analysis aims to evaluate the efficacy of metformin and exenatide, respectively, and to compare the efficacy of both drugs using Body Mass Index (BMI), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and testosterone level. Method: Scopus, Science Direct, Oxford Journal, Wiley Online Library, and Medline (through the PubMed search engine) were used in this study. Statistical analysis of the included studies was done using the RevMan 5.4 software. Results: There were 6 studies included in the analysis of the study. There was a significant reduction in BMI of PCOS patients with exenatide versus metformin (mean difference = 0.51; 95% confidence interval (CI)= 0.07, 0.96, I 2= 52%; p=0.02). There was also a significant reduction in the testosterone level of PCOS patients with exenatide versus met-formin (mean difference = 0.15; 95% confidence interval (CI)= 0.07, 0.22, I 2= 0%; p=0.0002). There was no effect on the mean of LDL-C and of HDL-C when compared between metformin and exenatide This meta-analysis shows that exenatide is effective in reducing BMI and testosterone levels in PCOS patients. Conclusions: There were a significant reduction in BMI and testosterone levels of PCOS patients when exenatide was used as compared to metformin. However, there was no effect on the mean of the LDL-C and HDL-C levels of the PCOS patients. (AU)

Role of Honey as a Bifunctional Reducing and Capping/Stabilizing Agent: Application for Silver and Zinc Oxide Nanoparticles.

The use of natural reducing and capping agents has gained importance as a way to synthesize nanoparticles (NPs) in an environmentally sustainable manner. Increasing numbers of studies have been published on the green synthesis of NPs using natural sources such as bacteria, fungi, and plants. In recent years, the use of honey in the synthesis of metal and metal oxide NPs has become a new and promising area of research. Honey acts as both a stabilizing and reducing agent in the NP synthesis process and serves as a precursor. This review focuses on the use of honey in the synthesis of silver NPs (Ag-NPs) and zinc oxide NPs (ZnO-NPs), emphasizing its role as a reducing and capping agent. Additionally, a comprehensive examination of the bio-based reducing and capping/stabilizing agents used in the honey-mediated biosynthesis mechanism is provided. Finally, the review looks forward to environmentally friendly methods for NP synthesis.

Cancer and Disease Diagnosis - Biosensor as Potential Diagnostic Tool for Biomarker Detection.

Analysis of cancer biomarkers has enormous promise for advancing our molecular understanding of illness and facilitating more precise and timely diagnosis and follow-up care. MicroRNA, exosomes, ctDNA, CTCs, and proteins are only some of the circulating biomarkers that can be detected by liquid biopsy instead of the more intrusive and time-consuming process of doing a tissue biopsy. As the cancer diagnosis bio-markers reveal ultra-low levels in the early stages of the disease, highly sensitive approaches are urgently required. Researchers have taken an interest in a optical biosensor for detecting cancer biomarkers as a potential tool for early disease diagnosis. These techniques have the potential to aid in the development of effective treatments, ultimately leading to a higher rate of patient survival. This review briefly discuss the i) understanding of cancer and biomarkers for early diagonosis purpose ii) Molecular methods and ii) biosensor-based diagnostics. The reseach primary focus on advancement in biosensor design using various concepts ie., Electrochemical, Chemiluminescence and Colorimetric, Surface plasmons (SP), Surface plasmon resonance (SPR), localized surface plasmon resonance (LSPR), Fluorescence, Fiber-based sensors, Terahertz based biosensors, and Surface enhanced Raman spectroscopy (SERS). As a result of the local electric field amplification around plasmonic (usually gold and silver) nanostructures, surface-enhanced Raman spectroscopy (SERS) has emerged as a rapid, selective, and sensitive alternative to conventional laboratory analytical methods, making significant strides in a number of biosensing applications but still under developing stage to be used as diagnostic tool in clinical research.

Cancer and Apoptosis.

Cancer is an uncontrolled growth of normal cells due to unchecked regulatory mechanisms working inside the rapidly dividing cells. In this complex cancer disease treatment, various strategies are utilized to get rid of cancer cells effectively. The different methods combine approaches used to treat cancer, such as radiotherapy, surgery, and chemotherapy. Chemotherapy is among the most effective ways, along with radiotherapy and surgical removal of cancer tissue. Effective chemotherapy based on modification of conventional drugs along with various molecular therapeutic targets, which involve different inhibitors that work in a specific manner in inhibiting particular events activated in cancer cells-the understanding of molecular signaling pathways holds key in the development of targeted therapeutics. After the fundamental signaling pathway studies, a single signaling pathway targeting approach or multiple targeting could display remarkable results in cancer therapeutics. The signal approach includes the signal pathway target. However, a double targeted pathway could effectively aid in inhibiting cell growth or metastasis either due to triggering natural suicidal mechanism (apoptosis) activation. The particular environment of cells regulates cell growth and differentiation. Various proteins in the extracellular matrix (ECM) regulate the process of cancer initiation or progression. The ECM collagens, elastins proteins, fibronectins, and laminins might reduce the effectiveness of treatment therapy, reflecting them as an essential target. Any dysregulation in the composition of ECM reflects the regulatory ineffectiveness in a particular area. These have an association with poor prognosis, cell propagation, and metastasis, along drug resistance.Regulation in physiological processes associated with developmental process and maintaining the homeostasis. The pathogenesis of cancer might be connected to dysregulation in cell death programs, including autophagy, necrosis, and the most desirable cell death mechanism called apoptosis: programmed cell death, the highly regulatory mechanism of natural cell death involved in tissue development. The apoptosis involves characteristic feather of cell death which includes specific morphological change along with biochemical alteration. It includes tightly regulated irreversible events, i.e., phosphatidylserine externalization and DNA fragmentation, mainly via the intrinsic and extrinsic pathways. Targeting apoptosis in the development of therapeutics could be the ultimate process in treating cancer via chemotherapy. During apoptosis, cell death occurs without causing much damage or inflammation in neighboring cells. Various pro-apoptosis and anti-apoptosis proteins involved in the regulation of apoptosis could act as a remarkable target. The apoptosis inactivation is the critical dysregulatory process in the majority of cancer types. There is an increase in research development regarding apoptosis-targeted therapeutics. A understanding of apoptotic signaling pathways, a fundamental knowledge, aids in developing particular inhibitors for anti-apoptotic and activator of pro-apoptotic proteins.In both apoptosis pathways (extrinsic and intrinsic), pro-apoptotic and anti-apoptotic proteins act as potential regulators in cell division and growth. The pro-apoptotic proteins Bax trigger the activation of the intrinsic pathway, an excellent target for developing therapeutics, and are currently in clinical trials. Similarly, the inhibitor of the anti-apoptotic proteins is also on track in the drug development process. The considerable importance of apoptosis-based anticancer drugs is also due to improving the drug sensitivity via reversing the resistive mechanisms in cancer cells. The dysregulatory or inactivated apoptosis mechanism involve Bcl-2 family proteins which include both pro-apoptotic members downregulation and anti-apoptotic upregulation, various inhibitors of apoptosis as inhibitory proteins (IAPs), cell cycle dysregulation, dysregulatory repair system, cell progression pathway activation of NF-κB, tumor suppressor (p53) regulation, and death receptors (DRs) of the extrinsic pathway.

Cancer and apoptosis: The apoptotic activity of plant and marine natural products and their potential as targeted cancer therapeutics.

Cancer is a multifactorial, multi-stage disease, including complex cascades of signaling pathways-the cell growth governed by dysregulated and abrupt cell division. Due to the complexity and multi-regulatory cancer progression, cancer is still a challenging disease to treat and survive. The screening of extracts and fractions from plants and marine species might lead to the discovery of more effective compounds for cancer therapeutics. The isolated compounds and reformed analogs were known as future prospective contenders for anti-cancer chemotherapy. For example, Taxol, a potent mitotic inhibitor discovered from Taxus brevifolia, suppresses cell growth and arrest, induces apoptosis, and inhibits proliferation. Similarly, marine sponges show remarkable tumor chemo preventive and chemotherapeutic potential. However, there is limited research to date. Several plants and marine-derived anti-cancer compounds having the property to induce apoptosis have been approved for clinical trials. The anti-cancer activity kills the cell and slows the growth of cancer cells. Among cell death mechanisms, apoptosis induction is a more profound mechanism of cell death triggered by naturally isolated anti-cancer agents. Evading apoptosis is the major hurdle in killing cancer cells, a mechanism mainly regulated as intrinsic and extrinsic. However, it is possible to modify the apoptosis-resistant phenotype of the cell by altering many of these mechanisms. Various extracts and fractions successfully induce apoptosis, cell-cycle modulation, apoptosis, and anti-proliferative activity. Therefore, there is a pressing need to develop new anti-cancer drugs of natural origins to reduce the effects on normal cells. Here, we've emphasized the most critical elements: i) A better understanding of cancer progression and development and its origins, ii) Molecular strategies to inhibit the cell proliferation/Carcino-genesis, iii) Critical regulators of cancer cell proliferation and development, iv) Signaling Pathways in Apoptosis: Potential Targets for targeted therapeutics, v) Why Apoptosis induction is mandatory for effective chemotherapy, vi) Plants extracts/fractions as potential apoptotic inducers, vii) Marine extracts as Apoptotic inducers, viii) Marine isolated Targeted compounds as Apoptotic inducers (FDA Approved/treatment Phase). This study provides a potential therapeutic option for cancer, although more clinical studies are needed to verify its efficacy in cancer chemotherapy.

Recent Advances in Honey-Based Nanoparticles for Wound Dressing: A Review.

Wounds with impaired healing, including delayed acute injuries and chronic injuries, generally fail to progress through normal healing stages. A deeper understanding of the biochemical processes involved in chronic wound cures is necessary to correct the microenvironmental imbalances in the wound treatment designs of products. The therapeutic benefits of honey, particularly its antimicrobial activity, make it a viable option for wound treatment in a variety of situations. Integration with nanotechnology has opened up new possibilities not only for wound healing but also for other medicinal applications. In this review, recent advances in honey-based nanoparticles for wound healing are discussed. This also covers the mechanism of the action of nanoparticles in the wound healing process and perspectives on the challenges and future trends of using honey-based nanoparticles. The underlying mechanisms of wound healing using honey are believed to be attributed to hydrogen peroxide, high osmolality, acidity, non-peroxide components, and phenols. Therefore, incorporating honey into various wound dressings has become a major trend due to the increasing demand for combination dressings in the global wound dressing market because these dressings contain two or more types of chemical and physical properties to ensure optimal functionality. At the same time, their multiple features (low cost, biocompatibility, and swelling index) and diverse fabrication methods (electrospun fibres, hydrogels, etc.) make them a popular choice among researchers.

A systematic review of health sciences students' online learning during the COVID-19 pandemic.

BACKGROUND: This study aims to analyse the effectiveness of distance learning during the COVID-19 pandemic among undergraduate health sciences students using systematic review. Online learning has been chosen as the best approach to continue offering education in this pandemic era. METHOD: The screening process was done using Scopus, ScienceDirect and PubMed based on the eligibility criteria. Out of 1486 studies, 1269 were screened. A total of 64 eligible studies obtained were included in the quantitative analysis. Results were categorized into i) student attitudes (perceptions/satisfactions/engagements), and ii) student learning outcomes, and compared to the Kirkpatrick model. RESULTS: Although facing difficulties, 50% of the studies was moderately satisfied with distance learning, while 36% was highly satisfied and 17% dissatisfied. Most studies (26%) reported flexibility in online learning. Internet issues (19%) and low interaction between learners and instructors (19%) were the most prevalent problems mentioned. Online education engages students better than traditional learning. The learning outcome was assessed using two categories: i) academic performance and ii) skill development. Most studies (72%) stated that online learning improves academic performance, 14% reported a drop, and 14% stated no effect, while an increase in clinical skills and communication skills were reported. Kirkpatrick evaluation revealed 80% of the studies obtained was evaluated at level 1 (reaction), 8% at level 2 (learning), 12% at level 3 (behaviour) and none at level 4 (results). CONCLUSION: Overall, this systematic review found that the online learning performed better than expected during COVID-19, but the data gained is insufficient to say it is beneficial when compared to other types of teaching approaches.

Anti-aging and antioxidant of four traditional malaysian plants using simplex centroid mixture design approach.

Aging is a naturally biological process with adverse effects. The continuous accumulation of reactive oxygen species (ROS) trigger cellular and tissue damage by activating several aging enzymes. The antioxidant properties of traditional medicinal plants used by Jakun aborigine's community are a promising approach to alleviate aging process and prevent Alzheimer. The aim of the current investigation was to optimize a novel anti-aging formulation from traditional plants (Cnestis palala stem, Urceola micrantha stem, Marantodes pumilum stem and Microporus xanthopus fruiting bodies) using simplex centroid mixture design (SCMD). After selecting the optimal formulations based on desirability function of antioxidant activity (DPPH, ABTS ˙ + and FRAP), they were further examined against the activity of aging-related-enzymes (collagenase, tyrosinase, acetyl- and butyrylcholinesterase). The single extracts of C. palala, U. micrantha and the binary mixture of C. palala and U. micrantha were the optimal formulations with high antioxidant activities. Single extract of U. micrantha showed the highest inhibition towards matrix metalloproteinase-1 (49.44 ± 4.11 %), while C. palala water extract showed highest inhibitions towards tyrosinase (14.06 ± 0.31%), acetylcholinesterase (32.92 ± 2.13%) and butyrylcholinesterase (34.89 ± 2.84%) enzymes. The single extracts of C. palala and U. micrantha displayed better activity as compared to the binary mixture formulation. In conclusion, these findings could be a baseline for further exploration of novel anti-aging agents from natural resources.

Breast Cancer: A Global Concern, Diagnostic and Therapeutic Perspectives, Mechanistic Targets in Drug Development.

Cancer is a complex multifactorial process, unchecked and abrupt division, and cell growth-conventional chemotherapy, along with radiotherapy, is used to treat breast cancer. Due to reduce efficacy and less survival rate, there is a particular need for the discovery of new active anticancer agents. Natural resources such as terrestrial/marine plants or organisms are a promising source for the generation of new therapeutics with improving efficacy. The screening of natural plant extracts and fractions, isolations of phytochemicals, and mechanistic study of those potential compounds play a remarkable role in the development of new therapeutic drugs with increased efficacy. Cancer is a multistage disease with complex signaling cascades. The initial study of screening whole extracts or fractions and later the isolation of secondary compounds and their mechanism of action study gives a clue of potential therapeutic agents for future drug development. The phytochemicals present in extracts/fractions produce remarkable effects due to synergistically targeting multiple signals. In this review, the molecular targets of extracts/ fractions and isolated compounds highlighted. The therapeutic agent's mechanistic targets in drug development focused involves; i) Induction of Apoptosis, ii) modulating cell cycle arrest, iii) Inhibition or suppression of invasion and metastasis and iv) various other pro-survival signaling pathways. The phytochemicals and their modified analogs identified as future potential candidates for anticancer chemotherapy.

Understanding Hyaluronan Receptor (CD44) Interaction, HA-CD44 Activated Potential Targets in Cancer Therapeutics.

Cancer is a complex mechanism involving a series of cellular events. The glycoproteins such as hyaluronan (HA) are a significant element of extracellular matrix (ECM), involve in the onset of cancer developmental process. The pivotal roles of HA in cancer progression depend on dysregulated expression in various cancer. HA, also gain attention due to consideration as a primary ligand of CD44 receptor. The CD44, complex transmembrane receptor protein, due to alternative splicing in the transcription process, various CD44 isoforms predominantly exist. The overexpression of distinct CD44 isoforms (CD44v) standard (CD44s) depends on the tumour type and stage. The receptor proteins, CD44 engage in a variety of biological processes, including cell growth, apoptosis, migration, and angiogenesis. HA-CD44 interaction trigger survival pathways that result in cell proliferation, invasion ultimately complex metastasis. The interaction and binding of ligand-receptor HA-CD44 regulate the downstream cytoskeleton pathways involve in cell survival or cell death. Thus, targeting HA, CD44 (variant and standard) isoform, and HA-CD44 binding consider as an attractive and useful approach towards cancer therapeutics. The use of various inhibitors of HA, hyaluronidases (HYALs), and utilizing targeted Nano-delivery of anticancer agents and antibodies against CD44, peptides gives promising results in vitro and in vivo. However, they are in clinical trials with favourable and unfavourable outcomes, which reflects the need for various modifications in targeting agents and a better understanding of potential targets in tumour progression pathways.

Approaches for Mitigating Microbial Biofilm-Related Drug Resistance: A Focus on Micro- and Nanotechnologies.

Biofilms play an essential role in chronic and healthcare-associated infections and are more resistant to antimicrobials compared to their planktonic counterparts due to their (1) physiological state, (2) cell density, (3) quorum sensing abilities, (4) presence of extracellular matrix, (5) upregulation of drug efflux pumps, (6) point mutation and overexpression of resistance genes, and (7) presence of persister cells. The genes involved and their implications in antimicrobial resistance are well defined for bacterial biofilms but are understudied in fungal biofilms. Potential therapeutics for biofilm mitigation that have been reported include (1) antimicrobial photodynamic therapy, (2) antimicrobial lock therapy, (3) antimicrobial peptides, (4) electrical methods, and (5) antimicrobial coatings. These approaches exhibit promising characteristics for addressing the impending crisis of antimicrobial resistance (AMR). Recently, advances in the micro- and nanotechnology field have propelled the development of novel biomaterials and approaches to combat biofilms either independently, in combination or as antimicrobial delivery systems. In this review, we will summarize the general principles of clinically important microbial biofilm formation with a focus on fungal biofilms. We will delve into the details of some novel micro- and nanotechnology approaches that have been developed to combat biofilms and the possibility of utilizing them in a clinical setting.

Secondary Metabolites, Antioxidant, and Antiproliferative Activities of Dioscorea bulbifera Leaf Collected from Endau Rompin, Johor, Malaysia.

Breast cancer is among the most commonly diagnosed cancer and the leading cause of cancer-related death among women globally. Malaysia is a country that is rich in medicinal plant species. Hence, this research aims to explore the secondary metabolites, antioxidant, and antiproliferative activities of Dioscorea bulbifera leaf collected from Endau Rompin, Johor, Malaysia. Antioxidant activity was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) assays, while the cytotoxicity of D. bulbifera on MDA-MB-231 and MCF-7 breast cancer cell lines was tested using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell cycle analysis and apoptosis were assessed using flow cytometry analysis. Phytochemical profiling was conducted using gas chromatography-mass spectrometry (GC-MS). Results showed that methanol extract had the highest antioxidant activity in DPPH, FRAP, and ABTS assays, followed by ethyl acetate and hexane extracts. D. bulbifera tested against MDA-MB-231 and MCF-7 cell lines showed a pronounced cytotoxic effect with IC50 values of 8.96 µg/mL, 6.88 µg/mL, and 3.27 µg/mL in MCF-7 and 14.29 µg/mL, 11.86 µg/mL, and 7.23 µg/mL in MDA-MB-231, respectively. Cell cycle analysis also indicated that D. bulbifera prompted apoptosis at various stages, and a significant decrease in viable cells was detected within 24 h and substantially improved after 48 h and 72 h of treatment. Phytochemical profiling of methanol extract revealed the presence of 39 metabolites such as acetic acid, n-hexadecanoic acid, acetin, hexadecanoate, 7-tetradecenal, phytol, octadecanoic acid, cholesterol, palmitic acid, and linolenate. Hence, these findings concluded that D. bulbifera extract has promising anticancer and natural antioxidant agents. However, further study is needed to isolate the bioactive compounds and validate the effectiveness of this extract in the In in vivo model.

Honey and its nutritional and anti-inflammatory value.

Inflammation is the main key role in developing chronic diseases including cancer, cardiovascular diseases, diabetes, arthritis, and neurodegenerative diseases which possess a huge challenge for treatment. With massively compelling evidence of the role played by nutritional modulation in preventing inflammation-related diseases, there is a growing interest into the search for natural functional foods with therapeutic and preventive actions. Honey, a nutritional healthy product, is produced mainly by two types of bees: honeybee and stingless bee. Since both types of honey possess distinctive phenolic and flavonoid compounds, there is recently an intensive interest in their biological and clinical actions against inflammation-mediated chronic diseases. This review shed the light specifically on the bioavailability and bioaccessibility of honey polyphenols and highlight their roles in targeting inflammatory pathways in gastrointestinal tract disorders, edema, cancer, metabolic and cardiovascular diseases and gut microbiota.

Acute Inflammation and Oxidative Stress Induced by Lipopolysaccharide and the Ameliorative Effect of Stingless Bee Honey.

BACKGROUND: Systemic acute inflammation is the hallmark of sepsis and is associated with multiple organ dysfunction. OBJECTIVE: This study investigated the potential of Stingless Bee Honey (SBH) to suppress lipopolysaccharide (LPS)-induced systemic acute inflammation in rats and to reveal the probable mechanism of action. METHODS: Rats received 4.6 and 9.2 g/kg SBH for 7 days followed by a single injection of LPS after which blood samples were taken 6h later. RESULTS: LPS induced liver, kidney, heart, and lung injury, were manifested by increased serum transaminases, alkaline phosphatase, creatine kinase, creatinine, and urea, along with multiple histological alterations, particularly leukocyte infiltration. Pro-inflammatory cytokines were elevated in the serum, and NF-κB p65, p38 MAPK, and HMGB-1 were significantly increased in different tissues of LPS-challenged rats. SBH prevented tissue injury, ameliorated pro-inflammatory cytokines, and suppressed NF-κB p65, p38 MAPK, and HMGB-1 in rats that had received LPS. In addition, SBH diminished reactive oxygen species (ROS) production, lipid peroxidation, and oxidative DNA damage, and enhanced glutathione and Nrf2 in LPS-treated rats. CONCLUSION: SBH prevents systemic acute inflammation by suppressing NF-κB, p38 MAPK, HMGB-1, oxidative stress, and tissue injury in rats. Thus, SBH may represent an effective anti-inflammatory nutraceutical, pending further mechanistic studies.