Initial report on the multiple biological and pharmacological properties of hispolon: Exploring stochastic mechanisms.

The development of natural substances derived from nature poses a significant challenge as technologies for the extraction and characterization of active principles advance. Hispolon has received a lot of attention in recent years, ascribable to its wide range of biological activities. It is a phenolic molecule that was extracted from several mushroom species such as Phellinus igniarius, Phellinus linteus, Phellinus lonicerinus, Phellinus merrillii, and Inonotus hispidus. To provide a comprehensive overview of the pharmacological activities of hispolon, this review highlights its anticancer, anti-inflammatory, antioxidant, antibacterial, and anti-diabetic activities. Several scientific research databases, including Google Scholar, Web of Science, PubMed, SciFinder, SpringerLink, Science Direct, Scopus, and, Wiley Online were used to gather the data on hispolon until May 2024. The in vitro and in vivo studies have revealed that hispolon exhibited significant anticancer properties through modifying several signaling pathways including cell apoptosis, cycle arrest, autophagy, and inhibition of angiogenesis and metastasis. Hispolon's antimicrobial activity was proven against many bacterial, fungal, and viral pathogens, highlighting its potential use as a novel antimicrobial agent. Additionally, hispolon displayed potent anti-inflammatory activity through the suppression of key inflammatory mediators, such as inducible NO synthase (iNOS), tumor necrosis factor-α (TNF-α), and cyclooxygenases-2 (COX-2), and the modulation of mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. The antioxidant potential of hispolon was attributed to its capacity to neutralize reactive oxygen species (ROS) and to increase the activity of antioxidant enzymes, indicating a possible involvement in the prevention of oxidative stress-related illnesses. Hispolon's antidiabetic activity was associated with the inhibition of aldose reductase and α-glucosidase. Studies on hispolon emphasized its potential use as a promising scaffold for the development of novel therapeutic agents targeting various diseases, including cancer, infectious diseases, inflammatory disorders, and diabetes.

Stochasticity of anticancer mechanisms underlying clinical effectiveness of vorinostat.

The Food and Drug Administration (FDA) has approved vorinostat, also called Zolinza®, for its effectiveness in fighting cancer. This drug is a suberoyl-anilide hydroxamic acid belonging to the class of histone deacetylase inhibitors (HDACis). Its HDAC inhibitory potential allows it to accumulate acetylated histones. This, in turn, can restore normal gene expression in cancer cells and activate multiple signaling pathways. Experiments have proven that vorinostat induces histone acetylation and cytotoxicity in many cancer cell lines, increases the level of p21 cell cycle proteins, and enhances pro-apoptotic factors while decreasing anti-apoptotic factors. Additionally, it regulates the immune response by up-regulating programmed death-ligand 1 (PD-L1) and interferon gamma receptor 1 (IFN-γR1) expression, and can impact proteasome and/or aggresome degradation, endoplasmic reticulum function, cell cycle arrest, apoptosis, tumor microenvironment remodeling, and angiogenesis inhibition. In this study, we sought to elucidate the precise molecular mechanism by which Vorinostat inhibits HDACs. A deeper understanding of these mechanisms could improve our understanding of cancer cell abnormalities and provide new therapeutic possibilities for cancer treatment.

Unlocking the combined action of Mentha pulegium L. essential oil and Thym honey: In vitro pharmacological activities, molecular docking, and in vivo anti-inflammatory effect.

Mentha pulegium L., a plant widely embraced for its therapeutic properties by populations worldwide, including Morocco, has long been recognized for its potential in treating various ailments. This study aims to comprehensively evaluate the antioxidant, anti-inflammatory, and dermatoprotective properties of essential oil derived from M. pulegium, and thyme honey as well as their combined effects. To unravel the chemical composition, a rigorous GC-MS analysis was conducted. Subsequently, we examined their antioxidant potential through three distinct assays: DPPH●, hydrogen peroxide assay, and xanthine oxidase assay. The anti-inflammatory properties were scrutinized through both in vitro and in vivo experiments. Simultaneously, the dermatoprotective efficacy was investigated in vitro by evaluating tyrosinase inhibition. Our findings revealed that pulegone constitutes the predominant compound in M. pulegium essential oil (MPEO), constituting a remarkable 74.82 % of the composition. Significantly, when the essential oil was combined with thym honey, it exhibited superior anti-inflammatory and dermatoprotective effects across all in vivo and in vitro tests. Moreover, our in silico molecular docking analysis hinted at the potential role of cyclohexanone, 3-methyl, an element found in the MPEO, in contributing to the observed outcomes. While this study has unveiled promising results regarding the combined in vitro, in vivo and in silico biological activities of the essential oil and honey, it is imperative to delve further into the underlying mechanisms through additional experimentation and alternative experimental methods. Understanding these mechanisms in greater detail will not only enhance our comprehension of the therapeutic potential but also pave the way for the development of innovative treatments and applications rooted in the synergy of these natural compounds. Furthermore, it would be advantageous to test different possible combinations using experimental design model. Moreover, it would be better to test the effect of single compounds of MPEO to clearly elucidate their efficiency. MPEO alone or combined with thyme honey may be a useful for the development of novel biopharmaceuticals.

Recent advances and molecular mechanisms of TGF-ß signaling in colorectal cancer, with focus on bioactive compounds targeting.

Colorectal cancer (CRC) is one of the most significant forms of human cancer. It is characterized by its heterogeneity because several molecular factors are involved in contiguity and can link it to others without having a linear correlation. Among the factors influencing tumor transformation in CRC, transforming growth factor-beta (TGF-ß) plays a key promoter role. This factor is associated with human colorectal tumors with a very high prognosis: it increases the survival, invasion, and metastasis of CRC cells, thus functioning as an oncogene. The inhibition of this factor can constitute a major therapeutic route for CRC treatment. Various chemical drugs including synthetic molecules and biotherapies have been developed as TGF-ß inhibitors. Moreover, the scientific community has recently shown a major interest in screening natural drugs inhibiting TGF-ß in CRC. In this context, we carried out this review article using computerized databases, such as PubMed, Google Scholar, Springer Link, Science Direct, Cochrane Library, Embase, Web of Science, and Scopus, to highlight the molecular mechanism of TGF-ß in CRC induction and progression and current advances in the pharmacodynamic effects of natural bioactive substances targeting TGF-ß in CRC.

Black soldier fly (Hermetia illucens L.): A potential small mighty giant in the field of cosmeceuticals.

Background and Aims: Natural products are widely used in the pharmaceutical and cosmetics industries due to their high-value bioactive compounds, which make for "greener" and more environmentally friendly ingredients. These natural compounds are also considered a safer alternative to antibiotics, which may result in antibiotic resistance as well as unfavorable side effects. The development of cosmeceuticals, which combine the cosmetic and pharmaceutical fields to create skincare products with therapeutic value, has increased the demand for unique natural resources. The objective of this review is to discuss the biological properties of extracts derived from larvae of the black soldier fly (BSF; Hermetia illucens), the appropriate extraction methods, and the potential of this insect as a novel active ingredient in the formulation of new cosmeceutical products. This review also addresses the biological actions of compounds originating from the BSF, and the possible association between the diets of BSF larvae and their subsequent bioactive composition. Methods: A literature search was conducted using PubMed and Google Scholar to identify and evaluate the various biological properties of the BSF. Results: One such natural resource that may be useful in the cosmeceutical field is the BSF, a versatile insect with numerous potential applications due to its nutrient content and scavenging behavior. Previous research has also shown that the BSF has several biological properties, including antimicrobial, antioxidant, anti-inflammatory, and wound healing effects. Conclusion: Given the range of biological activities and metabolites possessed by the BSF, this insect may have the cosmeceutical potential to treat a number of skin pathologies.

Adenovirus-mediated expression of MOAP-1, Bax and RASSF1A antagonizes chemo-drug resistance of human breast cancer cells expressing cancer stem cell markers.

Cancer is one of the major leading causes of mortality globally and chemo-drug-resistant cancers pose significant challenges to cancer treatment by reducing patient survival rates and increasing treatment costs. Although the mechanisms of chemoresistance vary among different types of cancer, cancer cells are known to share several hallmarks, such as their resistance to apoptosis as well as the ability of cancer stem cells to produce metastatic daughter cells that are resistant to chemotherapy. To address the issue of chemo-drug resistance in cancer cells, a tetracistronic expression construct, Ad-MBR-GFP, encoding adenovirus-mediated expression of MOAP-1, Bax, RASSSF1A, and GFP, was generated to investigate its potential activity in reducing or inhibiting the chemo-drug resistant activity of the human breast cancer cells, MCF-7-CR and MDA-MB-231. When infected by Ad-MBR-GFP, the cancer cells exhibited round cell morphology and nuclei condensation with positive staining for annexin-V. Furthermore, our results showed that both MCF-7-CR and MDA-MB-231 cells stained positively for CD 44 and negatively for CD 24 (CD44+/CD24-) with high levels of endogenous ALDH activity whereas SNU-1581 breast cancer cells were identified as CD 44-/CD 24- cells with relatively low levels of endogenous ALDH activity and high sensitivity toward chemo-drugs, suggesting that both CD 44 and ALDH activity contribute to chemo-drug resistance. Moreover, both MCF-7-CR and MDA-MB-231 cells showed strong chemo-drug sensitivity to cisplatin when the cells were infected by Ad-MBR-GFP, leading to 9-fold and 2-fold reduction in the IC 50 values when compared to cisplatin treatment alone, respectively. The data were further supported by 3D (soft agar) and spheroid cell models of MCF-7-CR and MDA-MB-231 cells which showed a 2-fold reduction of a number of cell colonies and spheroid size when treated with both Ad-MBR-GFP and cisplatin, and compared to control. Other than chemo-sensitivity, Ad-MBR-GFP-infected cancer cells retarded cell migration. Flow cytometry analysis showed that the mechanism of action of Ad-MBR-GFP involved cell cycle arrest at the G1 phase and inhibition of cellular DNA synthesis. Taken together, our investigation showed that Ad-MBR-GFP mediated chemo-drug sensitization in the infected cancer cells involved the activation of apoptosis signaling, cell cycle arrest, and inhibition of DNA synthesis, suggesting that Ad-MBR-GFP is potentially efficacious for the treatment of chemo-drug resistant cancers.

A systematic review of thromboembolic complications and outcomes in hospitalised COVID-19 patients.

Thromboembolic (TE) complications [myocardial infarction (MI), stroke, deep vein thrombosis (DVT), and pulmonary embolism (PE)] are common causes of mortality in hospitalised COVID-19 patients. Therefore, this review was undertaken to explore the incidence of TE complications and mortality associated with TE complications in hospitalised COVID-19 patients from different studies. A literature search was performed using ScienceDirect and PubMed databases using the MeSH term search strategy of "COVID-19", "thromboembolic complication", "venous thromboembolism", "arterial thromboembolism", "deep vein thrombosis", "pulmonary embolism", "myocardial infarction", "stroke", and "mortality". There were 33 studies included in this review. Studies have revealed that COVID-19 patients tend to develop venous thromboembolism (PE:1.0-40.0% and DVT:0.4-84%) compared to arterial thromboembolism (stroke:0.5-15.2% and MI:0.8-8.7%). Lastly, the all-cause mortality of COVID-19 patients ranged from 4.8 to 63%, whereas the incidence of mortality associated with TE complications was between 5% and 48%. A wide range of incidences of TE complications and mortality associated with TE complications can be seen among hospitalized COVID-19 patients. Therefore, every patient should be assessed for the risk of thromboembolic complications and provided with an appropriate thromboprophylaxis management plan tailored to their individual needs.

Clinical applications and mechanism insights of natural flavonoids against type 2 diabetes mellitus.

Diabetes is a complex disease that affects a large percentage of the world's population, and it is associated with several risk factors. Self-management poses a significant challenge, but natural sources have shown great potential in providing effective glucose reducing solutions. Flavonoids, a class of bioactive substances found in different natural sources including medicinal plants, have emerged as promising candidates in this regard. Indeed, several flavonoids, including apigenin, arbutin, catechins, and cyanidin, have demonstrated remarkable anti-diabetic properties. The clinical effectiveness of these flavonoids is linked to their potential to decrease blood glucose concentration and increase insulin concentration. Thus, the regulation of certain metabolic pathways such as glycolysis and neoglycogenesis has also been demonstrated. In vitro and in vivo investigations revealed different mechanisms of action related to flavonoid compounds at subcellular, cellular, and molecular levels. The main actions reside in the activation of glycolytic signaling pathways and the inhibition of signaling that promotes glucose synthesis and storage. In this review, we highlight the clinical efficiency of natural flavonoids as well as the molecular mechanisms underlying this effectiveness.

Consensus holistic virtual screening for drug discovery: a novel machine learning model approach.

In drug discovery, virtual screening is crucial for identifying potential hit compounds. This study aims to present a novel pipeline that employs machine learning models that amalgamates various conventional screening methods. A diverse array of protein targets was selected, and their corresponding datasets were subjected to active/decoy distribution analysis prior to scoring using four distinct methods: QSAR, Pharmacophore, docking, and 2D shape similarity, which were ultimately integrated into a single consensus score. The fine-tuned machine learning models were ranked using the novel formula "w_new", consensus scores were calculated, and an enrichment study was performed for each target. Distinctively, consensus scoring outperformed other methods in specific protein targets such as PPARG and DPP4, achieving AUC values of 0.90 and 0.84, respectively. Remarkably, this approach consistently prioritized compounds with higher experimental PIC50 values compared to all other screening methodologies. Moreover, the models demonstrated a range of moderate to high performance in terms of R2 values during external validation. In conclusion, this novel workflow consistently delivered superior results, emphasizing the significance of a holistic approach in drug discovery, where both quantitative metrics and active enrichment play pivotal roles in identifying the best virtual screening methodology.Scientific contributionWe presented a novel consensus scoring workflow in virtual screening, merging diverse methods for enhanced compound selection. We also introduced 'w_new', a groundbreaking metric that intricately refines machine learning model rankings by weighing various model-specific parameters, revolutionizing their efficacy in drug discovery in addition to other domains.

Insights into the computer-aided drug design and discovery based on anthraquinone scaffold for cancer treatment: A systematic review.

BACKGROUND: In the search for better anticancer drugs, computer-aided drug design (CADD) techniques play an indispensable role in facilitating the lengthy and costly drug discovery process especially when natural products are involved. Anthraquinone is one of the most widely-recognized natural products with anticancer properties. This review aimed to systematically assess and synthesize evidence on the utilization of CADD techniques centered on the anthraquinone scaffold for cancer treatment. METHODS: The conduct and reporting of this review were done in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 guideline. The protocol was registered in the "International prospective register of systematic reviews" database (PROSPERO: CRD42023432904) and also published recently. The search strategy was designed based on the combination of concept 1 "CADD or virtual screening", concept 2 "anthraquinone" and concept 3 "cancer". The search was executed in PubMed, Scopus, Web of Science and MedRxiv on 30 June 2023. RESULTS: Databases searching retrieved a total of 317 records. After deduplication and applying the eligibility criteria, the final review ended up with 32 articles in which 3 articles were found by citation searching. The CADD methods used in the studies were either structure-based alone (69%) or combined with ligand-based methods via parallel (9%) or sequential (22%) approaches. Molecular docking was performed in all studies, with Glide and AutoDock being the most popular commercial and public software used respectively. Protein data bank was used in most studies to retrieve the crystal structure of the targets of interest while the main ligand databases were PubChem and Zinc. The utilization of in-silico techniques has enabled a deeper dive into the structural, biological and pharmacological properties of anthraquinone derivatives, revealing their remarkable anticancer properties in an all-rounded fashion. CONCLUSION: By harnessing the power of computational tools and leveraging the natural diversity of anthraquinone compounds, researchers can expedite the development of better drugs to address the unmet medical needs in cancer treatment by improving the treatment outcome for cancer patients.

A phase II randomized, double-blind, placebo-controlled study of Nuvastatic (C50SEW505OESA), a standardized rosmarinic acid-rich polymolecular botanical extract formulation to reduce cancer-related fatigue in patients with solid tumors.

AIM: We evaluated the efficacy and safety of Nuvastatic™ (C5OSEW5050ESA) in improving cancer-related fatigue (CRF) among cancer patients. METHODS: This multicenter randomized double-blind placebo-controlled phase 2 trial included 110 solid malignant tumor patients (stage II-IV) undergoing chemotherapy. They were randomly selected and provided oral Nuvastatic™ 1000 mg (N = 56) or placebo (N = 54) thrice daily for 9 weeks. The primary outcomes were fatigue (Brief Fatigue Inventory (BFI)) and Visual Analog Scale for Fatigue (VAS-F)) scores measured before and after intervention at baseline and weeks 3, 6, and 9. The secondary outcomes were mean group difference in the vitality subscale of the Medical Outcome Scale Short Form-36 (SF-36) and urinary F2-isoprostane concentration (an oxidative stress biomarker), Eastern Cooperative Oncology Group scores, adverse events, and biochemical and hematologic parameters. Analysis was performed by intention-to-treat (ITT). Primary and secondary outcomes were assessed by two-way repeated-measures analysis of variance (mixed ANOVA). RESULTS: The Nuvastatic™ group exhibited an overall decreased fatigue score compared with the placebo group. Compared with the placebo group, the Nuvastatic™ group significantly reduced BFI-fatigue (BFI fatigue score, F (1.4, 147) = 16.554, p < 0.001, partial η2 = 0.333). The Nuvastatic™ group significantly reduced VAS-F fatigue (F (2, 210) = 9.534, p < 0.001, partial η2 = 0.083), improved quality of life (QoL) (F (1.2, 127.48) = 34.07, p < 0.001, partial η2 = 0.243), and lowered urinary F2-IsoP concentrations (mean difference (95% CI) = 55.57 (24.84, 86.30)), t (55) = 3.624, p < 0.001, Cohen's d (95% CI) = 0.48 (0.20, 0.75)). Reported adverse events were vomiting (0.9%), fever (5.4%), and headache (2.7%). CONCLUSION: Nuvastatic™ is potentially an effective adjuvant for CRF management in solid tumor patients and worthy of further investigation in larger trials. TRIAL REGISTRATION: ClinicalTrial.gov ID: NCT04546607. Study registration date (first submitted): 11-05-2020.

Influence of Maqian essential oil on gut microbiota and immunoresponses in type 1 diabetes: In silico study.

Diversity and homeostasis of gut bacterial composition is highly associated with the pathogenesis of insulin dysfunction and type 1 diabetes melittus (T1D), hence emerged in parallel with the activation of autoimmunity. We aimed to study the bioactive potential of essential oil from Zanthoxylum myriacanthum var. pubescens Huang (Maqian) through computational approaches. Twelve chemical constituents derived from Maqian essential oil were docked with selected proteins (i.e., 3pig, 1kho, 7dmq, 4m4d, 2z65, 4glp, and 3fxi) in which are involved in gut microbiota modulation in T1D. Subsequently, the prediction of bioavailability properties of the small molecules were evaluated. Among all chemical constituents, the post-docking interaction analysis demonstrated that α-phellandrene exhibits the strongest binding affinity and induces gut microbiota modulation with ß-fructofuranosidase from Bifidobacterium longum. The current result revealed the potential of 3-Carene and α-Pinene in inducing specific changes in gut microbiota downregulating Clostridium perfringens and quenching Leptotrichia shahii respectively. ß-Pinene possess exceptionally strong binding affinity that effectively disrupt the interaction between lipopolysaccharide and its cognate receptors, while α-Phellandrene was exhibited the uppermost binding affinity with TLR4/MD2 and could likely target TLR4 stimulating lipopolysaccharide. Our results are the first to report on the gut microbiota modulation effects of α-Phellandrene and ß-Phellandrene via actions on LPS binding to CD14 and the TLR4 co-receptor signaling. In conclusion, our findings based on computational approaches, small molecules from Maqian present as promising agents which could regulate inflammatory response and modulate gut microbiota in type 1 diabetes mellitus.

Application of Aleppo pine extract for skin burn treatment.

OBJECTIVE: To investigate the Pinus halepensis extracts and determine its healing and antibacterial effects, and to evaluate the treatment of skin burns. METHODS: Aqueous and ethanolic extracts and topical based on Aleppo pine plant extracts were prepared. Thirty male and female Wistar rats were used to study the cutaneous toxicity of extracts from the bark of P. halepensis. The extracts' healing potential for burn wounds were also assessed by evaluating the clinical and macroscopic aspects of the wounds. The antibacterial activity of crude extracts of P. halepensis as well as its wound healing abilities was verified in this investigation. RESULTS: In animals with acute dermal toxicity, there were no signs of treatment-related toxicity or death. The extracts of these plants could be transformed into phytomedicines for the treatment of infected wounds. The results demonstrated that formulated ointments are successful in treating second-degree burns in rats and may be suitable for the short-term therapeutic treatment of second-degree burns. CONCLUSION: This study successfully answered our problem, regarding the efficacy of our extract for treating second-degree burns in rats. Further studies are needed to confirm these results by identifying the molecules responsible for these activities and examining their mechanism of action.

Bioactive compounds from nature: Antioxidants targeting cellular transformation in response to epigenetic perturbations induced by oxidative stress.

Oxidative stress results from a persistent imbalance in oxidation levels that promotes oxidants, playing a crucial role in the early and sustained phases of DNA damage and genomic and epigenetic instability, both of which are intricately linked to the development of tumors. The molecular pathways contributing to carcinogenesis in this context, particularly those related to double-strand and single-strand breaks in DNA, serve as indicators of DNA damage due to oxidation in cancer cases, as well as factors contributing to epigenetic instability through ectopic expressions. Oxidative stress has been considered a therapeutic target for many years, and an increasing number of studies have highlighted the promising effectiveness of natural products in cancer treatment. In this regard, we present significant research on the therapeutic targeting of oxidative stress using natural molecules and underscore the essential role of oxidative stress in cancer. The consequences of stress, especially epigenetic instability, also offer significant therapeutic prospects. In this context, the use of natural epi-drugs capable of modulating and reorganizing the epigenetic network is beginning to emerge remarkably. In this review, we emphasize the close connections between oxidative stress, epigenetic instability, and tumor transformation, while highlighting the role of natural substances as antioxidants and epi-drugs in the anti-tumoral context.

Effectiveness of digital tools for smoking cessation in Asian countries: a systematic review.

AIM: The use of tobacco is responsible for many preventable diseases and deaths worldwide. Digital interventions have greatly improved patient health and clinical care and have proven to be effective for quitting smoking in the general population due to their flexibility and potential for personalization. However, there is limited evidence on the effectiveness of digital interventions for smoking cessation in Asian countries. METHODS: Three major databases - Web of Science (WOS), Scopus, and PubMed - for relevant studies published between 1 January 2010 and 12 February 2023 were searched for studies evaluating the effectiveness of digital intervention for smoking cessation in Asian countries. RESULTS: A total of 25 studies of varying designs were eligible for this study collectively involving a total of n = 22,005 participants from 9 countries. Among different digital tools for smoking cessation, the highest abstinence rate (70%) was reported with cognitive behavioural theory (CBT)-based smoking cessation intervention via Facebook followed by smartphone app (60%), WhatsApp (59.9%), and Pharmacist counselling with Quit US smartphone app (58.4%). However, WhatsApp was preferred over Facebook intervention due to lower rates of relapse. WeChat was responsible for 15.6% and 41.8% 7-day point prevalence abstinence. For telephone/text messaging abstinence rate ranged from 8-44.3% and quit rates from 6.3% to 16.8%. Whereas, no significant impact of media/multimedia messages and web-based learning on smoking cessation was observed in this study. CONCLUSION: Based on the study findings the use of digital tools can be considered an alternative and cost-effective smoking cessation intervention as compared to traditional smoking cessation interventions.

Self-reported side effects of COVID-19 vaccines among the public.

Background: The safety, side effects and efficacy profile of COVID-19 vaccines remain subjects of ongoing concern among the public in Malaysia. The aim of this study was to determine the types of adverse effects following immunisation with COVID-19 vaccines and the differences based on various types of COVID-19 vaccines to raise public awareness and reduce vaccine hesitancy among the public. Methods: A total of 901 Malaysian adults (≥18 years) who received various COVID-19 vaccines were selected to participate in our cross-sectional study through an online survey between December 2021 and January 2022. Results: A total of 814 (90.3%) of the participants reported ≥1 side effect following COVID-19 immunisation. Of these, the predominant symptoms were swelling at the injection site (n = 752, 83.5%), headache (n = 638, 70.8%), pain or soreness at the injection site (n = 628, 69.7%), fatigue or tiredness (n = 544, 60.4%), muscle weakness (n = 529, 58.7%) and diarrhea (n = 451, 50.1%). Recipients of the Pfizer-BioNTech (Comirnaty ®) vaccine reported the highest number of adverse effects (n = 355, 43.6%), followed by mixed COVID-19 vaccines (n = 254, 31.2%), the Oxford-AstraZeneca (ChAdOx1-®[recombinant]) vaccine (n = 113, 13.9%) and the Sinovac (CoronaVac®) vaccine (n = 90, 11.1%). The study showed that individuals who reported significantly more side effects were of elderly age, female gender and high educational level [P value < 0.05]. Mixed COVID-19 vaccine recipients also reported significantly more local and systemic symptoms after the first dose and third dose when compared with other single vaccine recipients. Conclusion: This study demonstrated the types of self-reported adverse effects following immunisation with single and mixed COVID-19 vaccines. These findings may provide the side effects of different COVID-19 vaccines with the hope of educating the public on the safety profiles of these vaccines and reducing vaccine hesitancy among the public.

Gas Chromatography-Mass Spectrometry (GC-MS) Analysis of Scaphium Affine Seed Extract and Assessment of its Anti-Hemorrhoidal Efficacy.

BACKGROUND: Seeds of plant Scaphium Affine are traditionally used by the healers of "India" for the treatment of piles. OBJECTIVE: The primary objective of the study was to assess the anti-hemorrhoidal potential of the ethanolic seed extract of Scaphium affine. METHODS: After the soxhlet extraction method, the seed extract from Scaphium affine was first submitted to phytochemical standardization and then GC-MS analysis. Rats were given Croton oil and Jatropha oil to develop hemorrhoids, and Scaphium affine seed extract (ESA) was administered orally for 5 days and 3 days, respectively, at doses of 1000 and 500 mg/kg. The Rectoanal coefficient (RAC) was calculated as an inflammatory marker. The hemorrhoidal tissues were also subjected to cytokine profiling, biochemical estimation and histopathology. RESULTS: ESA demonstrated the presence of flavonoids, saponins, phytosterols, phenols, and tannins. GCMS analysis elucidated the presence of hexadecanoic acid 2 hydroxy -1,3 propane diyl ester,9 Octadecanoic acid ethyl ester, Cyclohexane 1,4 di methyl cis, Farnesol isomer,1, E-11, Z-13 octa decatriene, Stigmasterol, N-(5 ethyl -1,3,4-thiadiazol-yl) benzamide, N, N Dinitro 1,3,5,7 tetraza bicyclo 93,3,1) as major phytoconstituents. The results depicted more potent anti-hemorrhoidal activity of ESA at 1000 mg/kg, p.o., which was evident through a decrease in RAC. A significant decline in the levels of IL-1ß, IL-6, and TNF-α expression was observed, along with the restoration of altered antioxidants and enzymes. Histopathological analysis confirmed the tissue recovery as it revealed minimal inflammation and decreased dilated blood vessels in treated animals. CONCLUSION: Based on the results it can be concluded that seeds of Scaphium affine showed significant anti-hemorrhoid agents which may be attributed to their anti-inflammatory and anti-oxidant potential due to the presence of certain phytoconstituents in it. The study also supports the traditional use of seeds of Scaphium affine for the first time in the treatment of hemorrhoids.

2D nanostructures: Potential in diagnosis and treatment of Alzheimer's disease.

Two-dimensional (2D) nanomaterials have garnered enormous attention seemingly due to their unusual architecture and properties. Graphene and graphene oxide based 2D nanomaterials remained the most sought after for several years but the quest to design superior 2D nanomaterials which can find wider application gave rise to development of non-graphene 2D materials as well. Consequently, in addition to graphene based 2D nanomaterials, 2D nanostructures designed using macromolecules (such as DNAs, proteins, peptides and peptoids), transition metal dichalcogenides, transition-metal carbides and/or nitrides (MXene), black phosphorous, chitosan, hexagonal boron nitrides, and graphitic carbon nitride, and covalent organic frameworks have been developed. Interestingly, these 2D nanomaterials have found applications in diagnosis and treatment of various diseases including Alzheimer's disease (AD). Although AD is one of the most debilitating neurodegenerative conditions across the globe; unfortunately, there remains a paucity of effective diagnostic and/or therapeutic intervention for it till date. In this scenario, nanomaterial-based biosensors, or therapeutics especially 2D nanostructures are emerging to be promising in this regard. This review summarizes the diagnostic and therapeutic platforms developed for AD using 2D nanostructures. Collectively, it is worth mentioning that these 2D nanomaterials would seemingly provide an alternative and intriguing platform for biomedical interventions.

Tetraclinis articulata (Vahl) Mast. essential oil as a promising source of bioactive compounds with antimicrobial, antioxidant, anti-inflammatory and dermatoprotective properties: In vitro and in silico evidence.

Tetraclinis articulata is a known traditional medicinal plant used to manage various ailments, such as diabetes, rheumatism and infectious diseases. This study aims to determine the chemical constituents of T. articulata essential oil (EO) and to evaluate its in vitro antibacterial, anti-candidal, antioxidant, anti-inflammatory and dermatoprotective properties. In addition, a computational docking approach was used to predict the potential antioxidant, antibacterial, antifungal, anti-inflammatory, and cytotoxic properties of the identified compounds. The volatile oil obtained by hydrodistillation was characterized using gas chromatography-mass spectrometry (GC-MS). The antioxidant activity of T. articulata EO was investigated using three complementary assays: DPPH, ABTS and FRAP. Lipoxygenase (5-LOX) and tyrosinase enzymes were used to assess the anti-inflammatory and dermatoprotective effects of this oil. Moreover, disc-diffusion technique, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays were employed for the antimicrobial screening. The GC-MS analysis revealed that bornyl acetate (41.80 %), α-pinene (17.97 %) and camphor (15.97 %) are the major components of the studied EO. Moreover, T. articulata EO has exhibited promising antioxidant effect on FRAP, DPPH, and ABTS experiments. It also significantly inhibited 5-LOX (IC50 = 67.82 ± 0.03 µg/mL) and tyrosinase (IC50 = 211.93 ± 0.02 µg/mL). The results of MIC and MBC assays indicated that T. articulata EO is able to inhibit the growth of all tested bacteria (Gram + and Gram -) and Candida species. The ratio of tolerance level indicated that the tested oil was bactericidal against the Gram + bacteria and Candida species, whereas it has a bacteriostatic behavior against the Gram- bacteria. In light of these findings, T. articulata EO may be suggested as a potential pharmaceutical agent to prevent inflammation and skin problems and may serve as a natural antimicrobial and antioxidant alternative for sustainable application in food products.

The Use of ChatGPT for Education Modules on Integrated Pharmacotherapy of Infectious Disease: Educators' Perspectives.

BACKGROUND: Artificial Intelligence (AI) plays an important role in many fields, including medical education, practice, and research. Many medical educators started using ChatGPT at the end of 2022 for many purposes. OBJECTIVE: The aim of this study was to explore the potential uses, benefits, and risks of using ChatGPT in education modules on integrated pharmacotherapy of infectious disease. METHODS: A content analysis was conducted to investigate the applications of ChatGPT in education modules on integrated pharmacotherapy of infectious disease. Questions pertaining to curriculum development, syllabus design, lecture note preparation, and examination construction were posed during data collection. Three experienced professors rated the appropriateness and precision of the answers provided by ChatGPT. The consensus rating was considered. The professors also discussed the prospective applications, benefits, and risks of ChatGPT in this educational setting. RESULTS: ChatGPT demonstrated the ability to contribute to various aspects of curriculum design, with ratings ranging from 50% to 92% for appropriateness and accuracy. However, there were limitations and risks associated with its use, including incomplete syllabi, the absence of essential learning objectives, and the inability to design valid questionnaires and qualitative studies. It was suggested that educators use ChatGPT as a resource rather than relying primarily on its output. There are recommendations for effectively incorporating ChatGPT into the curriculum of the education modules on integrated pharmacotherapy of infectious disease. CONCLUSIONS: Medical and health sciences educators can use ChatGPT as a guide in many aspects related to the development of the curriculum of the education modules on integrated pharmacotherapy of infectious disease, syllabus design, lecture notes preparation, and examination preparation with caution.