Genetic variants associated with dengue hemorrhagic fever. A systematic review and meta-analysis.

Dengue hemorrhagic fever (DHF) is a severe condition resulting from the dengue virus, with four serotypes known as DEN-1, DEN-2, DEN-3, and DEN-4. Genetic variations play a crucial role in influencing susceptibility to DHF. Therefore, this investigation conducted a meta-analysis to uncover genetic changes that might have remained undetected in individual studies due to small sample sizes or methodological differences. Among 2212 initially identified studies, 23 were deemed suitable for analysis based on PRISMA guidelines. Toll-like receptors (TLR) and CD209 showed significant association with DHF (odds ratios: TLR=0.56, CD209 =0.55), indicating protective effects. However, tumor necrosis factor (TNF) and human leukocyte antigen (HLA) did not exhibit a statistically significant relationship with DHF. This study emphasizes the relevance of TLR and CD209 in DHF susceptibility and resistance across diverse geographical locations.

Diverse Pharmacological Potential of different Substituted Pyrazole Derivatives.

The chemistry of heterocyclic compounds has been a topic of research interest. Some five-membered heterocyclic compounds have been the subject of extensive research due to their different types of pharmacological effects. The five-membered nitrogen-containing heterocyclic compounds pyrazole, pyrazoline, and pyrazolone derivatives have a lot of interest in the fields of medical and agricultural chemistry due to their diverse spectrum of therapeutic activities. Various substituted pyrazole, pyrazoline, and pyrazolone compounds exhibited diverse pharmacological effects like Anti-microbial, anti-inflammatory, anti-tubercular, anti-fungal, anti-malarial, anti-di-abetic, diuretic, anti-depressant, anticonvulsant, antioxidant, anti-leishmanial, antidiabetic, and antiviral, etc. In recent decades, the synthesis of numerous pyrazole, pyrazoline, and pyrazolone derivatives by different synthetic methods as well as research into their chemical and biological behavior have become more important. This review focuses on synthetic methods of the pyrazole, pyrazoline, and pyrazolone derivatives, which have significant biological properties and a variety of applications.

Isoform switching leads to downregulation of cytokine producing genes in estrogen receptor positive breast cancer.

Objective: Estrogen receptor breast cancer (BC) is characterized by the expression of estrogen receptors. It is the most common cancer among women, with an incidence rate of 2.26 million cases worldwide. The aim of this study was to identify differentially expressed genes and isoform switching between estrogen receptor positive and triple negative BC samples. Methods: The data were collected from ArrayExpress, followed by preprocessing and subsequent mapping from HISAT2. Read quantification was performed by StringTie, and then R package ballgown was used to perform differential expression analysis. Functional enrichment analysis was conducted using Enrichr, and then immune genes were shortlisted based on the ScType marker database. Isoform switch analysis was also performed using the IsoformSwitchAnalyzeR package. Results: A total of 9,771 differentially expressed genes were identified, of which 86 were upregulated and 117 were downregulated. Six genes were identified as mainly associated with estrogen receptor positive BC, while a novel set of ten genes were found which have not previously been reported in estrogen receptor positive BC. Furthermore, alternative splicing and subsequent isoform usage in the immune system related genes were determined. Conclusion: This study identified the differential usage of isoforms in the immune system related genes in cancer cells that suggest immunosuppression due to the dysregulation of CXCR chemokine receptor binding, iron ion binding, and cytokine activity.

Diverse pharmacological potential of pyridazine analogs against various diseases.

Pyridazinone analogs possess diverse types of pharmacological activities, such as anticancer, antimicrobial, anticonvulsant, analgesic, anti-inflammatory, antioxidant, antihypertensive, antisecretory, antiulcer, and other useful pharmacological activities. They also possess cyclooxygenase (COX) inhibitors, dipeptidyl peptidase inhibitors, phosphodiesterase inhibitors, glutamate transporter activators, adenosine receptor antagonists, serotonin receptors antagonists, lipooxygenase, cholinesterase, vasodilator, and anesthetics. Pyridazine rings are the essential structure for some marketed drugs, such as pimobendan, levosimendan as a cardiotonic drug, and emorfozan as an analgesic and anti-inflammatory (Non-steroidal anti-inflammatory drug) agent. So, researchers all over the world have paid attention to synthesizing various pyridazinone compounds mainly due to the ease of design and synthesis of different analogs and variables in the pharmacological responses. This review article focuses on the pharmacological activities of different pyridazine analogs.

Eco-friendly synthesized nanoparticles as antimicrobial agents: an updated review.

Green synthesis of NPs has gained extensive acceptance as they are reliable, eco-friendly, sustainable, and stable. Chemically synthesized NPs cause lung inflammation, heart problems, liver dysfunction, immune suppression, organ accumulation, and altered metabolism, leading to organ-specific toxicity. NPs synthesized from plants and microbes are biologically safe and cost-effective. These microbes and plant sources can consume and accumulate inorganic metal ions from their adjacent niches, thus synthesizing extracellular and intracellular NPs. These inherent characteristics of biological cells to process and modify inorganic metal ions into NPs have helped explore an area of biochemical analysis. Biological entities or their extracts used in NPs include algae, bacteria, fungi, actinomycetes, viruses, yeasts, and plants, with varying capabilities through the bioreduction of metallic NPs. These biosynthesized NPs have a wide range of pharmaceutical applications, such as tissue engineering, detection of pathogens or proteins, antimicrobial agents, anticancer mediators, vehicles for drug delivery, formulations for functional foods, and identification of pathogens, which can contribute to translational research in medical applications. NPs have various applications in the food and drug packaging industry, agriculture, and environmental remediation.

ß Pore-forming Protein-based Evolutionary Divergence of Gnathostomata from Agnatha.

INTRODUCTION: The first vertebrates were jawless fish, or Agnatha, whose evolution diverged into jawed fish, or Gnathostomes, around 550 million years ago. METHODS: In this study, we investigated ß PFT proteins' evolutionary divergence of lamprey immune protein from Agnatha, reportedly possessing anti-cancer activity, into Dln1 protein from Gnathostomes. Both proteins showed structural and functional divergence, and shared evolutionary origin. Primary, secondary and tertiary sequences were compared to discover functional domains and conserved motifs in order to study the evolution of these two proteins. The structural and functional information relevant to evolutionary divergence was revealed using hydrophobic cluster analysis. RESULTS: The findings demonstrate that two membrane proteins with only a small degree of sequence identity can have remarkably similar hydropathy profiles, pointing towards conserved and similar global structures. When facing the lipid bilayer or lining the pore lumen, the two proteins' aerolysin domains' corresponding residues displayed a similar and largely conserved pattern. Aerolysin-like proteins from different species can be identified using a fingerprint created by PIPSA analysis of the pore-forming protein. CONCLUSION: We were able to fully understand the mechanism of action during pore formation through structural studies of these proteins.

Computational formulation of a multiepitope vaccine unveils an exceptional prophylactic candidate against Merkel cell polyomavirus.

Merkel cell carcinoma (MCC) is a rare neuroendocrine skin malignancy caused by human Merkel cell polyomavirus (MCV), leading to the most aggressive skin cancer in humans. MCV has been identified in approximately 43%-100% of MCC cases, contributing to the highly aggressive nature of primary cutaneous carcinoma and leading to a notable mortality rate. Currently, no existing vaccines or drug candidates have shown efficacy in addressing the ailment caused by this specific pathogen. Therefore, this study aimed to design a novel multiepitope vaccine candidate against the virus using integrated immunoinformatics and vaccinomics approaches. Initially, the highest antigenic, immunogenic, and non-allergenic epitopes of cytotoxic T lymphocytes, helper T lymphocytes, and linear B lymphocytes corresponding to the virus whole protein sequences were identified and retrieved for vaccine construction. Subsequently, the selected epitopes were linked with appropriate linkers and added an adjuvant in front of the construct to enhance the immunogenicity of the vaccine candidates. Additionally, molecular docking and dynamics simulations identified strong and stable binding interactions between vaccine candidates and human Toll-like receptor 4. Furthermore, computer-aided immune simulation found the real-life-like immune response of vaccine candidates upon administration to the human body. Finally, codon optimization was conducted on the vaccine candidates to facilitate the in silico cloning of the vaccine into the pET28+(a) cloning vector. In conclusion, the vaccine candidate developed in this study is anticipated to augment the immune response in humans and effectively combat the virus. Nevertheless, it is imperative to conduct in vitro and in vivo assays to evaluate the efficacy of these vaccine candidates thoroughly. These evaluations will provide critical insights into the vaccine's effectiveness and potential for further development.

PEGylated Graphene Oxide as a Nanodrug Delivery Vehicle for Podophyllotoxin (GO/PEG/PTOX) and In Vitro α-Amylase/α-Glucosidase Inhibition Activities.

This study aims to develop a nanodrug delivery system containing podophyllotoxin (PTOX), a known anticancer drug, loaded on graphene oxide (GO). The system's ability to inhibit α-amylase and α-glucosidase enzymes was also investigated. PTOX was isolated from Podophyllum hexandrum roots with a yield of 2.3%. GO, prepared by Hummer's method, was converted into GO-COOH and surface-mobilized using polyethylene glycol (PEG) (1:1) in an aqueous medium to obtain GO-PEG. PTOX was loaded on GO-PEG in a facile manner with a 25% loading ratio. All the samples were characterized using FT-IR spectroscopy, UV/visible spectroscopy, and scanning electron microscopy (SEM). In FT-IR spectral data, GO-PEG-PTOX exhibited a reduction in acidic functionalities and there was an appearance of the ester linkage of PTOX with GO. The UV/visible measurements suggested an increase of absorbance in 290-350 nm regions for GO-PEG, suggesting the successful drug loading on its surface (25%). GO-PEG-PTOX exhibited a rough, aggregated, and scattered type of pattern in SEM with distinct edges and binding of PTOX on its surface. GO-PEG-PTOX remained potent in inhibiting both α-amylase and α-glucosidase with IC50 values of 7 and 5 mg/mL, closer to the IC50 of pure PTOX (5 and 4.5 mg/mL), respectively. Owing to the 25% loading ratio and 50% release within 48 h, our results are much more promising. Additionally, the molecular docking studies confirmed four types of interactions between the active centers of enzymes and PTOX, thus supporting the experimental results. In conclusion, the PTOX-loaded GO nanocomposites are promising α-amylase- and α-glucosidase-inhibitory agents when applied in vitro and have been reported for the first time.

g-C3N4 Based Photocatalyst for the Efficient Photodegradation of Toxic Methyl Orange Dye: Recent Modifications and Future Perspectives.

Industrial effluents containing dyes are the dominant pollutants, making the drinking water unfit. Among the dyes, methylene orange (MO) dye is mutagenic, carcinogenic and toxic to aquatic organisms. Therefore, its removal from water bodies through effective and economical approach is gaining increased attention in the last decades. Photocatalytic degradation has the ability to convert economically complex dye molecules into non-toxic and smaller species via redox reactions, by using photocatalysts. g-C3N4 is a metal-free n-type semiconductor, typical nonmetallic and non-toxici polymeric photocatalyst. It widely used in photocatalytic materials, due to its easy and simple synthesis, fascinating electronic band structure, high stability and abundant availability. As a photocatalyst, its major drawbacks are its limited efficiency in separating photo-excited electron-hole pairs, high separated charge recombination, low specific surface area, and low absorption coefficient. In this review, we report the recent modification strategies adopted for g-C3N4 for the efficient photodegradation of MO dye. The different modification approaches, such as nanocomposites and heterojunctions, as well as doping and defect introductions, are briefly discussed. The mechanism of the photodegradation of MO dye by g-C3N4 and future perspectives are discussed. This review paper will predict strategies for the fabrication of an efficient g-C3N4-based photocatalyst for the photodegradation of MO dye.

Intranasal Delivery of a Silymarin Loaded Microemulsion for the Effective Treatment of Parkinson's Disease in Rats: Formulation, Optimization, Characterization, and In Vivo Evaluation.

A mucoadhesive microemulsion of lipophilic silymarin (SLMMME) was developed to treat Parkinson's disease (PD). Optimization of the SLM microemulsion (ME) was performed using Central Composite Design (CCD). The composition of oil, surfactant, co-surfactant, and water was varied, as per the design, to optimize their ratio and achieve desirable droplet size, zeta potential, and drug loading. The droplet size, zeta potential, and drug loading of optimized SLMME were 61.26 ± 3.65 nm, -24.26 ± 0.2 mV, and 97.28 ± 4.87%, respectively. With the addition of chitosan, the droplet size and zeta potential of the developed ME were both improved considerably. In vitro cell toxicity investigations on a neuroblastoma cell line confirmed that SLMMME was non-toxic and harmless. In comparison to ME and drug solution, mucoadhesive ME had the most flow through sheep nasal mucosa. Further, the in vitro release showed significantly higher drug release, and diffusion of the SLM loaded in MEs than that of the silymarin solution (SLMS). The assessment of behavioral and biochemical parameters, as well as inflammatory markers, showed significant (p < 0.05) amelioration in their level, confirming the significant improvement in neuroprotection in rats treated with SLMMME compared to rats treated with naïve SLM.

Multi-objective deep learning framework for COVID-19 dataset problems.

Background: It has been reported that a deadly virus known as COVID-19 has arisen in China and has spread rapidly throughout the country. The globe was shattered, and a large number of people on the planet died. It quickly became an epidemic due to the absence of apparent symptoms and causes for patients, confusion appears due to the lack of sufficient laboratory results, and its intelligent algorithms were used to make decisions on clinical outcomes. Methods: This study developed a new framework for medical datasets with high missing values based on deep-learning optimization models. The robustness of our model is achieved by combining: Data Missing Care (DMC) Framework to overcome the problem of high missing data in medical datasets, and Grid-Search optimization used to develop an improved deep predictive training model for patients with COVID-19 by setting multiple hyperparameters and tuning assessments on three deep learning algorithms: ANN (Artificial Neural Network), CNN (Convolutional Neural Network), and Recurrent Neural Networks (RNN). Results: The experiment results conducted on three medical datasets showed the effectiveness of our hybrid approach and an improvement in accuracy and efficiency since all the evaluation metrics were close to ideal for all deep learning classifiers. We got the best evaluation in terms of accuracy 98%, precession 98.5%, F1-score 98.6%, and ROC Curve (95% to 99%) for the COVID-19 dataset provided by GitHub. The second dataset is also Covid-19 provided by Albert Einstein Hospital with high missing data after applying our approach the accuracy reached more than 91%. Third dataset for Cervical Cancer provided by Kaggle all the evaluation metrics reached more than 95%. Conclusions: The proposed formula for processing this type of data can replace the traditional formats in optimization while providing high accuracy and less time to classify patients. Whereas, the experimental results of our approach, supported by comprehensive statistical analysis, can improve the overall evaluation performance of the problem of classifying medical data sets with high missing values. Therefore, this approach can be used in many areas such as energy management, environment, and medicine.

Seroprevalence of IgM and IgG Against SARS-CoV-2 after Two Doses of Pfizer-BioNTech COVID-19 Vaccine in Women with Breast Cancer.

BACKGROUND: This study evaluates the seroprevalence of immunoglobulin M (IgM) and G (IgG) antibodies against SARS-CoV-2 after two doses of Pfizer-BioNTech COVID-19 vaccination from women with breast cancer in Jazan city Kingdom of Saudi Arabia, antibody detections were performed one month and three months after the administration of the second dose. METHODS: Overall, 103 breast cancer patients were included. Individuals who had had two doses of Pfizer-BioNTech vaccine, patients who were earlier diagnosed with COVID-19 infection, had not finalized immunization plan, or who received the second dose recently were excluded from the study. The antibodies detection test was run according to the manufacturer's directions of Viva Diag™ SARS-CoV-2 IgM/IgG Rapid Test (COVID-19 IgM/IgG Rapid Test). RESULTS: This study included 62 (60.2%) and 41 (39.8%) patients with invasive ductal carcinoma and invasive lobular carcinoma, respectively. The age, median and interquartile range (IQR) was 54.0 (26) years. Regarding reactivity of antibodies, after one month IgM antibody showed 64 (62.1%) positive and 39 (37.9%) negative while IgG antibody showed positive results in all patients. After three months IgM antibody showed 44 (42.7%) positive and 59 (57.3%) negative, while IgG showed 87 (84.5%) positive and 16 (15.5%) negative. There were significant differences in the IgM and IgG seropositivity. There were 19.3% patients with ductal carcinoma who were positive and then turned negative versus 17.7% who were positive and then turned negative, respectively (p < 0.001). There were significant differences in IgM antibody positivity among different age groups. CONCLUSIONS: Our results recommend the importance of screening for an antibody response for breast cancer patient after immunization in order to reveal persons who need early and late extra enhancing vaccine dose. Upcoming studies recommended to estimate different methods that raise cancer patients' immune response.

An Evaluation of Antimicrobial, Anticancer, Anti-Inflammatory and Antioxidant Activities of Silver Nanoparticles Synthesized from Leaf Extract of Madhuca longifolia Utilizing Quantitative and Qualitative Methods.

In the current decade, nanoparticles are synthesized using solvents that are environmentally friendly. A number of nanoparticles have been synthesized at room temperature using water as a solvent, such as gold (Au) and silver (Ag) nanoparticles. As part of nanotechnology, nanoparticles are synthesized through biological processes. Biological methods are the preferred method for the synthesis of inorganic nanoparticles (AgNPs) as a result of their simple and non-hazardous nature. Nanoparticles of silver are used in a variety of applications, including catalysts, spectrally selective coatings for solar absorption, optical objectives, pharmaceutical constituents, and chemical and biological sensing. Antimicrobial agents are among the top uses of silver nanoparticles. In the current study, silver nanoparticles were biologically manufactured through Madhuca longifolia, and their antibacterial activity against pathogenic microorganisms, anticancer, anti-inflammatory, and antioxidant activities were assessed. UV-Vis spectroscopy, XRD (X-ray diffraction), transmission electron microscopy, Zeta Potential, and FTIR were used to characterize silver nanoparticles. The current work describes a cheap and environmentally friendly method to synthesize silver nanoparticles from silver nitrate solution by using plant crude extract as a reducing agent.

Evaluation of CD4+:CD8+ Ratio in Patients With Cervical Cancer and the Levels of Inflammatory Markers.

BACKGROUND/AIM: Cervical cancer remains a major public health concern. The ratio of CD4+:CD8+ T-cells is used to evaluate the immune system function. This study aimed to explore the CD4+:CD8+ T-cell ratio in relation to the glycemic status, inflammatory markers, vitamin D, and vitamin B12 in patients with early diagnosed cervical cancer. PATIENTS AND METHODS: This is a cross-sectional study. Blood samples were collected for flow cytometry analysis. Information regarding Papanicolaou (Pap) smears and colposcopy investigations were collected from 152 women with type 2 diabetes admitted to East Jeddah Hospital, Jeddah, Saudi Arabia, between January 2018 and January 2021. RESULTS: Patients with early cervical carcinoma and a higher CD4+:CD8+ ratio (>1.2) had a higher C-reactive protein (CRP) level than those with a lower CD4+:CD8+ ratio (Mean±SD=13.75±13.3 vs. 10.85±8.1; p-value=0.034). Patients with early cervical carcinoma, diabetes, and higher CD4+:CD8+ ratio (>1.2) had a higher blood HbA1c percent than those with a lower CD4+:CD8+ ratio. CONCLUSION: A high CD4+:CD8+ T-cells ratio was associated with an increased HbA1c% and CRP levels in women with diabetes diagnosed with early cervical carcinoma, which can induce inflammation in early diagnosed patients with cervical cancer.

Physicochemical properties, nutrient profile, microbial stability, and sensory evaluation of cupcakes enriched with pomegranate seed oil.

Excessive use of refined flour, solid fats, and sugar in preparing baked products are considered to be unhealthy and is intricately linked with the development of lifestyle diseases. Replacing refined flour with whole wheat flour and solid fats with cold-pressed oil serves as an alternate option. The study was aimed at evaluating the physicochemical properties, nutrient composition, sensory attributes, and shelf life of cupcakes enriched using pomegranate seed oil (PSO). Vanilla and chocolate cupcake variants were prepared using 25 and 50% of PSO. A sensory panel consisting of 30 semi-trained participants was selected for evaluating the formulated products using a five-point hedonic scale. Nutrient content was estimated using standard techniques. The stability of the formulated product was determined by evaluating the physicochemical traits and microbial growth on the 0th, 4th, and 7th day. Mean scores of the sensorial analysis showed that the incorporation of PSO in cupcakes was highly accepted by the panel members. Chocolate cupcake containing 50% of PSO was found to be the most preferred product (3.53±0.94), followed by vanilla cupcake containing 25% of PSO (3.4±0.62). The moisture, protein, and fat content of chocolate cupcakes containing 25% of PSO were high. Cupcakes prepared with PSO can be stored for four days at room temperature. GC-MS analysis showed the presence of punicic acid, oleic acid, tocopherols, campesterol, sitosterols, stigmasterol, and α-tocopheryl acetate as pre-dominant fatty acid in unheated and heated PSO. In conclusion, cupcakes prepared using PSO showed acceptable physicochemical qualities and sensory properties which indicated its successful consumption by people affected with metabolic disorders.

Phthalimide Analogs Enhance Genotoxicity of Cyclophosphamide and Inhibit Its Associated Hypoxia.

Cyclophosphamide (CP) is a mutagen that is used in cancer chemotherapy, due to its genotoxicity and as an immunosuppressive agent. Thalidomide (TH) is another cancer chemotherapeutic drug. In this study, the cytogenotoxicity and hypoxia modulatory activities of two phthalimide analogs of TH have been evaluated with/without CP. Both analogs have increased CP-stimulated chromosomal aberrations than those induced by TH, including gaps, breaks/fragments, deletions, multiple aberrations, and tetraploidy. The analogs have elevated the cytotoxic effect of CP by inhibiting the mitotic activity, in which analog 2 showed higher mitosis inhibition. CP has induced binucleated and polynucleated bone marrow cells (BMCs), while micronuclei (MN) are absent. TH and analogs have elevated the CP-stimulated binucleated BMCs, while only analogs have increased the CP-induced polynucleated BMCs and inhibited the mononucleated BMCs. MN-BMCs were shown together with mononucleated, binucleated, and polynucleated cells in the CP group. Both analogs have elevated mononucleated and polynucleated MN-BMCs, whereas in presence of CP, TH and analogs have enhanced mononucleated and binucleated MN-BMCs. The analogs significantly induce DNA fragmentation in a comet assay, where analog 1 is the strongest inducer. The treatment of mice with CP has resulted in a high hypoxia status as indicated by high pimonidazole adducts and high HIF-1α and HIF-2α concentrations in lymphocytes. Analogs/CP-treated mice showed low pimonidazole adducts. Both analogs have inhibited HIF-1α concentration but not HIF-2α. Taken together, the study findings suggest that both analogs have a higher potential to induce CP-genotoxicity than TH and that both analogs inhibit CP-hypoxia via the HIF-1α-dependent mechanism, in which analog 1 is a more potent anti-hypoxic agent than analog 2. Analog 1 is suggested as an adjacent CP-complementary agent to induce CP-genotoxicity and to inhibit CP-associated hypoxia.

Vitamin D and Hypoxia-Inducible Factor (HIF-1α) Serum Levels as Markers for Progression of Nephropathy in Type 2 Diabetic Patients.

BACKGROUND: Vitamin D is a locally acting hormone, which plays a major role in skeletal health. Previous studies reported an important role of vitamin D in modulation of inflammatory response. We aimed to investigate the role of vitamin D deficiency and hypoxia-inducible factor (HIF-1α) as markers for the progression of diabetic nephropathy in Saudi patients with type 2 diabetes mellitus (T2DM). METHODS: We included 174 Saudi patients with T2DM in addition to 60 healthy control subjects. Patients were classified according to urinary Albumin to Creatinine Ratio (ACR) into three groups: Group AI: ACR < 30 µg/mg, Group AII: ACR levels of 30 - 300 µg/mg and Group AIII: ACR > 300 µg/mg. We estimated fasting blood glucose, HbA1c, lipid profile, serum creatinine, hemoglobin concentration (Hb), estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio, serum 25 hydroxyvitamin D, calcium, parathyroid hormone (PTH), tumor necrosis factor (TNF-α), C- reactive protein (CRP), and hypoxia-inducible factor (HIF-1α). RESULTS: There was a significant difference among studied groups regarding serum levels of vitamin D, calcium, PTH, TNF-α, CRP, and HIF-1α levels. The level of vitamin D was lower in diabetic patients in comparison to the controls and was significantly related to the severity of renal nephropathy as indicated by the level of albumin in urine. Moreover, vitamin D levels showed significant negative correlation with the inflammatory markers: TNF-α, CRP, and HIF-1α levels. CONCLUSIONS: Vitamin D deficiency and elevated HIF-1α serum levels showed a significant correlation to progression of nephropathy in Saudi patients with T2DM.

Anti-hypoxic Effect of Polysaccharide Extract of Brown Seaweed Sargassum dentifolium in Tongue Squamous Cell Carcinoma.

Sargassum dentifolium, (Turner) C. Agarth, 1820, is an edible brown alga collected from red seashores, Egypt. Oral tongue squamous cell carcinoma (OTSCC) is an aggressive malignancy. Hypoxia leads to chemotherapeutic resistance. This work aimed to explore the anti-hypoxia effect of water-soluble polysaccharide fractions of S. dentifolium (SD1-SD3) in CAL-27 OTSCC cells. Cell cytotoxicity assay (MTT); cell death mode (DNA staining); total hypoxia (pimonidazole), HIF-1α (ELISA and immunocytochemistry), HIF-1ß (ELISA), and hsa-miRNA-21-5p and hsa-miRNA-210-3p (qRT-PCR) were investigated. SD1 and SD2 showed a cytotoxic effect due to apoptosis. SD2 and SD3 decreased total cell hypoxia, inhibited miR-210 (p < 0.001 and p < 0.01), miR-21 (p < 0.01 and p < 0.05), and HIF-1α (p < 0.01 and p < 0.05), respectively. However, only SD3 suppressed HIF-1ß (p < 0.05). In conclusion, SD2 showed a potential anti-hypoxia effect through amelioration of HIF-1α regulators, which may help in decreasing hypoxia-induced therapeutic resistance.

Eco-Friendly Synthesis of MnO2 Nanorods Using Gmelina arborea Fruit Extract and Its Anticancer Potency Against MCF-7 Breast Cancer Cell Line.

INTRODUCTION: Cancer disease is known due to its unregulated proliferation of cells that have evolved from the body's regular cells. The disease develops as a result of epigenetic and genetic modifications, tumor suppressor gene inactivation, and oncogene activation. The present work describes an environmentally benign approach for the synthesis of manganese oxide nanoparticles (MnO2 NPs) using Gmelina arborea fruit extract (GAE) in an aqueous medium. METHODS: The study evaluated the formation of MnO2 NPs and their anticancer efficacy against MCF-7 breast cancer cell line. RESULTS: The formation of MnO2 NPs was confirmed through powder X-ray diffractometer (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HR-TEM). The crystalline nature of as-prepared MnO2 NPs was evident from XRD pattern. The morphology of the material was studied using SEM analysis, which suggested a rod-like nature with an average diameter of 50 nm. Further, the TEM and HR-TEM images confirmed the rod shape of the as-prepared MnO2 NPs with an interplanar distance of 0.271 nm. In addition, the concentric rings from selected area electron diffraction (SAED) analysis show the crystalline nature of the as-prepared material, which further supports the obtained XRD pattern. The anticancer efficacy of MnO2 NPs was evaluated against MCF-7 breast cancer cell line, which showed up to 96% inhibition of the cells at 400 µg/mL concentration. CONCLUSION: Bio-conjugation of MnO2 NPs can provide enough scope for the therapeutic use of Gmelina arborea, assuming appropriate mechanistic evaluations are conducted.

Insulinotropic Potential of Moxifloxacin and Gemifloxacin: An In Vivo Rabbits Model Study Followed by Randomized Phase I Clinical Trial.

Fluoroquinolones (FQs) have been reported to cause dysglycemia in both diabetic and non-diabetic patients. However, diabetic patients are usually on polypharmacy, so we cannot attribute the dysglycemia specifically to FQs. To answer the question as to whether Moxifloxacin and Gemifloxacin influence blood glucose levels and serum insulin levels or otherwise, rabbits were used as experimental animals in an in vivo model followed by a phase I randomized clinical trial in euglycemic healthy volunteers. The effects on the serum insulin and blood glucose levels in the Moxifloxacin and Gemifloxacin treated groups were, respectively, determined on the fifth day in both the in-vivo rabbits model and in the test subjects of the phase I clinical trial. The effects of these drugs were also checked on the histomorphology of the pancreas in the rabbits. The findings of our study suggest that Moxifloxacin and Gemifloxacin significantly (p < 0.05) reduced the blood glucose levels via a subsequent significant shift in the serum insulin levels both in the in vivo animal model and in the test subjects of the phase I clinical trial. No prominent effects on the beta cells histomorphology were noted in this study. Moxifloxacin showed a more significant effect than Gemifloxacin. The insulinotropic effect was comparable to the effect of Glibenclamide. It is concluded that Moxifloxacin and Gemifloxacin have a significant blood glucose lowering effect mediated through insulinotropic action. (Clinical Trials.gov identifier: NCT04692623).