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This study explored the antiproliferative activity of naproxen at the molecular level in human breast cancer cell lines, specifically MCF-7. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed medications worldwide. Like other NSAIDs, naproxen has anti-inflammatory, analgesic, and antipyretic properties. The cytotoxic effects of naproxen on MCF-7 breast cancer cells were assessed using MTT cytotoxicity and lactate dehydrogenase (LDH) leakage assays. Additionally, quantitative reverse transcription PCR (qRT-PCR) was employed to evaluate the expression of apoptosis-related genes, including p53, caspases-3, 8, and 9, Bax, and Bcl 2. The anti-migratory effects of naproxen on breast cancer cells were investigated using a scratch assay. The H2DCFDA (H2-DCF, DCF) cellular assay was used to estimate the intracellular generation of reactive oxygen species (ROS) in breast cancer cells. Results indicated a significant decrease in the viability of MCF-7 cells, as highlighted by both the MTT cytotoxicity and LDH release assays. Compared to the untreated control cells, there was an overexpression of p53 and increased activities of caspases 3, 8, and 9. Bax was significantly upregulated, while Bcl-2 showed significant downregulation. Naproxen also significantly inhibited the migration of MCF-7 cells, as evidenced by the increased distance between the opposing edges of the scratch. In comparison, naproxen enhanced the intracellular generation of ROS in breast cancer cells. Based on these findings, it can be concluded that naproxen exhibits both antiproliferative and anti-migratory activities in the human breast cancer cell line MCF-7. Therefore, naproxen may be considered a promising candidate as an anti-cancer agent, especially when used in combination with other breast cancer therapies.

Objective: To evaluate the anticancer potential of Cymbopogon citratus extract. Methods: GC-MS analysis was used to identify phytocomponents in the methanolic extract of Cymbopogon citratus. A fractionation method was employed to isolate and assess the bioactivity of different fractions and their cytotoxic activities against cancer cell lines HCT116, LoVo, Caco-2, and HT-29 were investigated. A dual staining method with acridine orange and ethidium bromide was used to assess the effect of the extract on cell apoptosis. Additionally, the expression levels of Bax and TP53 were quantified using realtime PCR in Caco-2 cells treated with the ethyl acetate fraction of Cymbopogon citratus extract. A protein array was employed to profile key pro- and anti-apoptotic proteins in Caco-2 cells. Moreover, molecular docking studies were conducted to investigate the interactions between key compounds of Cymbopogon citratus extract and specific apoptosis-related protein domains (PDB IDs: 7wql and 4bkx). Results: A significant growth inhibition was observed in Caco-2 cells treated with Cymbopogon citratus extract. Among the seven fractions of the plant extract, the ethyl acetate fraction showed the highest cytotoxicity against Caco-2 cells with an IC50 value of (6.16 ± 0.01) μg/mL. The immunofluorescence assay showed that the ethyl acetate fraction could induce apoptosis of Caco-2 cells. Moreover, the fraction upregulated the gene expressions of Bax and TP53 in a dose-dependent manner. The docking analysis demonstrated the interaction of five compounds isolated from the ethyl acetate fraction with key proteins in Caco-2 cells, indicating their anticancer properties. Conclusions: Cymbopogon citratus extract shows anticancer activity against Caco-2 cells by inducing apoptosis. It may be a promising candidate for the treatment of colon cancer, which needs further investigation.

Arbuscular mycorrhizal (AM) fungi - Glomeromycota and Endogonomycetes - comprise multiple species and higher-level taxa that have remained undescribed. We propose a mixed morphology- and DNA-based classification framework to promote taxonomic communication and shed light into the phylogenetic structure of these ecologically essential fungi. Based on eDNA samples and long reads as type materials, we describe 15 new species and corresponding genera (Pseudoentrophospora kesseensis, Hoforsa rebekkae, Kahvena rebeccae, Kelottijaervia shannonae, Kungsaengena shadiae, Langduoa dianae, Lehetua indrekii, Lokruma stenii, Moostea stephanieae, Nikkaluokta mahdiehiae, Parnigua craigii, Riederberga sylviae, Ruua coralieae, Tammsaarea vivikae and Unemaeea nathalieae), the genus Parvocarpum as well as 19 families (Pseudoentrophosporaceae, Hoforsaceae, Kahvenaceae, Kelottijaerviaceae, Kungsaengenaceae, Langduoaceae, Lehetuaceae, Lokrumaceae, Moosteaceae, Nikkaluoktaceae, Parniguaceae, Riederbergaceae, Ruuaceae, Tammsaareaceae, Unemaeeaceae, Bifigurataceae, Planticonsortiaceae, Jimgerdemanniaceae and Vinositunicaceae) and 17 orders (Hoforsales, Kahvenales, Kelottijaerviales, Kungsaengenales, Langduoales, Lehetuales, Lokrumales, Moosteales, Nikkaluoktales, Parniguales, Riederbergales, Ruuales, Tammsaareales, Unemaeeales, Bifiguratales and Densosporales), and propose six combinations (Diversispora bareae, Diversispora nevadensis, Fuscutata cerradensis, Fuscutata reticulata, Viscospora deserticola and Parvocarpum badium) based on phylogenetic evidence. We highlight further knowledge gaps in the phylogenetic structure of AM fungi and propose an alphanumeric coding system for preliminary communication and reference-based eDNA quality-filtering of the remaining undescribed genus- and family-level groups. Using AM fungi as examples, we hope to offer a sound, mixed framework for classification to boost research in the alpha taxonomy of fungi, especially the “dark matter fungi”.

Numerous novel concepts in fractional mathematics have been created to provide numerical models for a variety of real-world, engineering, and scientific challenges because of the kernel's memory and non-local effects. In this post, we have looked at a deadly illness known as rabies. For our analysis, we employed the Atangana–Baleanu fractional derivative in Caputo sense. Additionally, the mathematical answer was obtained by applying the Laplace transform. Our approach is distinct, and we illustrated the vital role immunizations play in limiting the spread of the illness using graphical data. Furthermore, in this article, we have shown that fractional order systems are preferable to integer order systems.

The purpose of this study is to explore the impact of Ramucirumab alone and combined with 5-Aza on different cellular targets in human hepatocellular carcinoma cell line (HuH-7). Cells were treated with diverse concentrations of Ramucirumab (50, 100, 150 µg/mL) for 24 h. viability, levels of reactive oxygen species (ROS), antioxidant activities, mitochondrial membrane potential (MMP), DNA fragmentation, and expression of apoptotic genes (Caspases 3, 7, 9, p53, Bax, and Bcl-2) were measured. Results showed that HuH-7 cell viability was reduced in dose-dependent way with Ramucirumab therapy. Both Ramucirumab and 5-Aza elevated ROS, but their combination reduced ROS levels, though still higher than controls. Ramucirumab decreased SOD activity; while 5-Aza increased it. Combined therapy potentially increased SOD and CAT activities. Ramucirumab alone was not responsible to influence GSH levels, but 5-Aza and the combination treatments increased GSH levels. All treatments reduced the JC-1 aggregate/monomer ratio, indicating decreased MMP and potential apoptosis induction. High fragmentated DNA and condensation of chromatin were recorded suggesting apoptosis. Both agents, either as monotherapy or combined therapy, upregulated Caspases 3, 7, and 9, p53, and Bax expression, with variable effects on Bcl-2. In conclusion, Ramucirumab, particularly when co-administered with 5-Aza, effectively reduces viability of cells and prompts apoptosis in HuH-7 cells through increased oxidative stress, disturbance of MMP, and apoptotic pathways activation. The combination treatment shows potential for enhanced therapeutic efficacy against hepatocellular cancer cells.

IntroductionFusarium wilt, caused by Fusarium oxysporum f. sp. cubense (Foc), poses a significant global threat to banana cultivation. Conventional methods of disease management are increasingly challenged, thus making it necessary to explore alternative strategies. Bacterial endophytes, particularly from resistant genotypes, are gaining attention as potential biocontrol agents. Sphingobacterium thalpophilum, isolated from the resistant banana cultivar Pisang lilin (JALHSB010000001-JALHSB010000029), presents an intriguing prospect for combating Fusarium wilt. However, its underlying biocontrol mechanisms remain poorly understood. This study aimed to elucidate the antifungal efficacy of S. thalpophilum NMS02 S296 against Foc and explore its biocontrol mechanisms at the genomic level.MethodsWhole genome sequencing of S. thalpophilum NMS02 S296 was conducted using next-generation sequencing technologies and bioinformatics analyses were performed to identify genes associated with antifungal properties. In vitro assays were used to assess the inhibitory effects of the bacterial isolate on the mycelial growth of Foc. To explore the biomolecules responsible for the observed antagonistic activity, metabolites diffused into the agar at the zone of inhibition between Foc S16 and S. thalpophilum NMS02 S296 were extracted and identified.ResultsWhole genome sequencing revealed an array of genes encoding antifungal enzymes and secondary metabolites in S. thalpophilum NMS02 S296. In vitro experiments demonstrated significant inhibition of Foc mycelial growth by the bacterial endophyte. Comparative genomic analysis highlighted unique genomic features in S. thalpophilum linked to its biocontrol potential, setting it apart from other bacterial species.DiscussionThe study underscores the remarkable antifungal efficacy of S. thalpophilum NMS02 S296 against Fusarium wilt. The genetic basis for its biocontrol potential was elucidated through whole genome sequencing, shedding light on the mechanisms behind its antifungal activity. This study advanced our understanding of bacterial endophytes as biocontrol agents and offers a promising avenue for plant growth promotion towards sustainable strategies to mitigate Fusarium wilt in banana cultivation.

KDM2B, a histone lysine demethylase, is expressed in a plethora of cancers. Earlier studies from our group, have showcased that overexpression of KDM2B in the human prostate cancer cell line DU-145 is associated with cell adhesion, actin reorganization, and improved cancer cell migration. In addition, we have previously examined changes of cytosolic Ca2+, regulated by the pore-forming proteins ORAI and the Ca2+ sensing stromal interaction molecules (STIM), via store-operated Ca2+ entry (SOCE) in wild-type DU-145. This study sought to evaluate the impact of KDM2B overexpression on the expression of key molecules (SGK1, Nhe1, Orai1, Stim1) and SOCE. Furthermore, this is the first study to evaluate KDM2B expression in circulating tumor cells (CTCs) from patients with prostate cancer. mRNA levels for SGK1, Nhe1, Orai1, and Stim1 were quantified by RT-PCR. Calcium signals were measured in KDM2B-overexpressing DU-145 cells, loaded with Fura-2. Blood samples from 22 prostate cancer cases were scrutinized for KDM2B expression using immunofluorescence staining and the VyCAP system. KDM2B overexpression in DU-145 cells increased Orai1, Stim1, and Nhe1 mRNA levels and significantly decreased Ca2+ release. KDM2B expression was examined in 22 prostate cancer patients. CTCs were identified in 45 % of these patients. 80 % of the cytokeratin (CK)-positive patients and 63 % of the total examined CTCs exhibited the (CK + KDM2B + CD45−) phenotype. To conclude, this study is the first to report increased expression of KDM2B in CTCs from patients with prostate cancer, bridging in vitro and preclinical assessments on the potentially crucial role of KDM2B on migration, invasiveness, and ultimately metastasis in prostate cancer.

Introduction: Previous publications have shown that STIM1, ORAI1, and KDM2B, are implicated in Ca2+ signaling and are highly expressed in various cancer subtypes including prostate cancer. They play multiple roles in cancer cell migration, invasion, and metastasis. In the current study we investigated the expression of the above biomarkers in circulating tumor cells from patients with metastatic prostate cancer.Methods: Thirty-two patients were enrolled in this study and CTCs’ isolation was performed with Ficoll density gradient. Two different triple immunofluorescence stainings were conducted with the following combination of antibodies: CK/KDM2B/CD45 and CK/STIM1/ORAI1. Slides were analyzed using VyCAP microscopy technology.Results: CTC-positive patients were detected in 41% for (CK/KDM2B/CD45) staining and in 56% for (CK/STIM1/ORAI1) staining. The (CK+/KDM2B+/CD45–) and the (CK+/STIM1+/ORAI1+) were the most frequent phenotypes as they were detected in 85% and 94% of the CTC-positive patients, respectively. Furthermore, the expression of ORAI1 and STIM1 in patients’ PBMCs was very low exhibiting them as interesting specific biomarkers for CTC detection. The (CK+/STIM1+/ORAI1+) phenotype was correlated to bone metastasis (p = 0.034), while the (CK+/STIM1+/ORAI1–) to disease relapse (p = 0.049).Discussion: STIM1, ORAI1, and KDM2B were overexpressed in CTCs from patients with metastatic prostate cancer. STIM1 and ORAI1 expression was related to disease recurrence and bone metastasis. Further investigation of these biomarkers in a larger cohort of patients will clarify their clinical significance for prostate cancer patients.

Tomato, the important vegetable crop, is severely affected by Orthotospovirus arachinecrosis which impacts heavy economic losses. The application of insecticide to manage viral diseases is not an environmentally safe approach. In view of these issues, we investigated the antiviral efficacy of 21 bacterial endophytes against GBNV in local lesion host (Cowpea-VBN3). Based on the reduction in lesion number and virus titer as estimated through both DAC ELISA and qPCR in cowpea, the bacterial endophytes viz., Bacillus licheniformis Soya1, Bacillus tequilensis NBL6, and Bacillus velezensis VB7 were selected and further tested in tomato. The study revealed the well-defined antiviral efficacy of these endophytes against GBNV. The percentage of disease incidence ranged from 16 to 24% in endophyte-treated tomato plants compared with untreated plants (88%). In addition, symptom severity was reduced, and the application of endophytes also in promotion of the growth compared with untreated control. DAC ELISA revealed that the tomato plants treated with bacterial endophytes challenged with GBNV showed reduction in the virus titer (0.26–0.39 @ OD 405 nm) at different days of interval after inoculation (0, 5, and 10 days) compared with untreated control (3.475 @ OD 405 nm). Additionally, reduction in the viral copy number in bacterial endophyte-treated plants was evident by real-time PCR. Furthermore, tomato plants bacterized with endophytes depicted significant correlation and reduction in viral load and disease incidence as revealed by the principal-component biplot analysis. Thus, the application of bacterial endophytes has a potential role in reducing the disease incidence, severity, and titer value of GBNV, which will be the promising management approach in future to mitigate the virus infection in tomato plants.

BackgroundTinea capitis (T. capitis), commonly known as scalp ringworm, is a fungal infection affecting the scalp and hair. Among the causative agents, Microsporum canis (M. canis) stands out, often transmitted from cats to humans (zoonotic disease). In this study, we investigated the efficacy of Carica papaya (C. papaya), fruit extract against dermatophytes, particularly M. canis, both in vitro and in vivo. Additionally, we aimed to identify the active compounds responsible for suppressing fungal growth and assess the toxicity of C. papaya on human cells.MethodologyIt conducted in two parts. First, In Vitro Study include the preparation of C. papaya fruit extract using methanol as the solvent, Phytochemical analysis of the plant extract including Gas chromatography–mass spectrometry (GC–MS) and Fourier-transform infrared spectroscopy (FTIR) was conducted, Cytotoxicity assays were performed using HUH-7 cells, employing the MTT assay (1-(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), Antimicrobial activity against M. canis was evaluated, including: Zone of inhibition (ZI), Minimum inhibitory concentration (MIC), Minimum fungicidal concentration (MFC), M. canis cell alterations were observed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Second, In Vivo, Albino Wistar male rats were included.ResultsThe phytochemical analysis of the methanolic extract from papaya revealed several functional groups, including hydroxyl, ammonia, alkane, carbonate, and alcohol. Additionally, the GC–MS analysis identified 15 compounds, with xanthosine and decanoic acid being the predominant components. The methanolic extract of papaya fruits demonstrated potent antifungal activity: ZI = 37 mm, MIC = 1,000 μg/mL, MFC = 1900 μg/mL, MTT results indicated lower cytotoxicity of the fruit extract at concentrations of 20 μg/mL, 50 μg/mL, 100 μg/mL, 150 μg/mL, and 200 μg/mL, The IC50 revealed a significant decrease in cell viability with increasing extract concentration. Notably, papaya extract induced considerable alterations in the morphology of M. canis hyphae and spores. In animal tissue, improvements were observed among the group of rats which treated with Papaya extract. This study highlights the potential of C. papaya fruits as a natural antifungal agent, warranting further exploration for clinical applications.

In this article, a diffusion component in an SIR model is introduced, and its impact is analyzed using fractional calculus. We have included the diffusion component in the SIR model. in order to illustrate the variations. Here, we have applied the general fractional derivative to analyze the impact. The Laplace decomposition technique is employed to obtain the numerical outcomes of the model. In order to observe the effect of the diffusion component in the SIR model, graphical solutions are also displayed.

Abstract Arachis hypogaea is an allotetraploid crop widely grown in the world. Wild relatives of genus Arachis are the rich source of genetic diversity and high levels of resistance to combat pathogens and climate change. The accurate identification and characterization of plant resistance gene, nucleotide binding site leucine rich repeat receptor (NLRs) substantially contribute to the repertoire of resistances and improve production. In the current study, we have studied the evolution of NLR genes in genus Arachis and performed their comparative genomics among four diploids (A. duranensis, A. ipaensis, A. cardenasii, A. stenosperma) and two tetraploid (wild: A. monticola and domesticated: A. hypogaea) species. In total 521, 354, 284, 794, 654, 290 NLR genes were identified from A. cardenasii, A. stenosperma and A. duranensis, A. hypogaea, A. monticola and A. ipaensis respectively. Phylogenetic analysis and classification of NLRs revealed that they belong to 7 subgroups and specific subgroups have expanded in each genome leading towards divergent evolution. Gene gain and loss, duplication assay reveals that wild and domesticated tetraploids species have shown asymmetric expansion of NLRome in both sub-genome (AA and BB). A-subgenome of A. monticola exhibited significant contraction of NLRome while B-subgenome shows expansion and vice versa in case of A. hypogaea probably due to distinct natural and artificial selection pressure. In addition, diploid species A. cardenasii revealed the largest repertoire of NLR genes due to higher frequency of gene duplication and selection pressure. A. cardenasii and A. monticola can be regarded as putative resistance resources for peanut breeding program for introgression of novel resistance genes. Findings of this study also emphasize the application neo-diploids and polyploids due to higher quantitative expression of NLR genes. To the best of our knowledge, this is the first study that studied the effect of domestication and polyploidy on the evolution of NLR genes in genus Arachis to identify genomic resources for improving resistance of polyploid crop with global importance on economy and food security.

Worldwide, there has been an increasing prevalence of kidney disorders for several years. Kidney disorders are characterized by abnormal kidney biomarkers like uric acid, urea, cystatin C, creatinine, kidney injury molecule-1, C-related protein, etc., in the human body. A person suffering from kidney disorders is prone to several other serious health consequences, such as cardiac diseases and renal failure, which can lead to death. However, early diagnosis of kidney disorders requires effective disease management to prevent disease progression. Existing diagnostic techniques used for monitoring kidney biomarker concentration include chromatographic assays, spectroscopic assays, immunoassays, magnetic resonance imaging (MRI), computed tomography (CT), etc. They also necessitate equipped laboratory infrastructure, specific instruments, highly trained personnel working on these instruments, and monitoring kidney patients. Hence, these are expensive and time-consuming. Since the past few decades, a number of biosensors, like electrochemical, optical, immunosensors, potentiometric, colorimetric, etc., have been used to overcome the drawbacks of conventional and modern techniques. These biosensing systems have many benefits, such as being cost-effective, quick, simple, highly sensitive, specific, requiring a minimum sample amount, reliable, and easy to miniaturize. This review article discusses the uses of effectual biosensors for kidney biomarker detection with their potential advantages and disadvantages. Future research needs to be implicated in developing highly advanced biosensors that must be sensitive, economical, and simple so that they can be used for on-site early detection of kidney biomarkers to assess kidney function.

Lateral epicondylitis is a relatively common non-traumatic elbow disorder. It is a painful musculoskeletal condition that usually follows forceful repetitive pronation and supination. The aim of this study was to evaluate the advantages of ultrasound-guided injection in patients of Lateral Epicondylitis in comparison to non-image-guided blind injections. This comparative observational study was conducted on sixty patients who had clinical diagnosis of Lateral Epicondylitis. They were divided into two groups of thirty each (randomization done on odd even manner), one group underwent US-guided injections and the other group underwent the blind procedure by a specialist. Pain relief using the Visual Analog Scale (VAS) {score of 0–10} was recorded before the procedure, immediately after the procedure, one-week post-procedure, and six weeks post-procedure. Demographic characteristics, chief complaints, duration of symptoms, previous treatment taken, and complications post-procedure were gathered and compared between the two groups. All patients in both groups finished the period of study. Significant improvement in pain score and tenderness was found in both groups immediately after the injection, one-week post-procedure, and after six weeks post-procedure when compared to the baseline value (p value

The tumor suppressor gene (TP53) is crucial for DNA repair mechanism, apoptosis, and cell cycle regulation and progression. In human cancer, TP53 is mutated and highly polymorphic. In the current case-control research investigation, we investigated TP53 gene SNPs, in exonic and intronic regions, as potential risk factors for colorectal cancer (CRC). This study comprised of 192 patients and 192 control. Obtained data illustrated that only the G allele; rs1042522 (Pro72Arg (C > G), demonstrated a statistically significant association, almost 1.5-fold induction promotes the risk of CRC development in contrast to individuals with the C allele (OR = 1.5, χ2 = 7.28, p = 0.00696). The homozygous variant GG genotype of rs1042522 was also a significant risk factor to CRC development (OR = 2.1, χ2 = 6.41, p = 0.01136). SNP rs1042522 polymorphism established a considerably elevated odds of CRC among male patients aged

Cadmium (Cd) is an environmental and industrial toxicant that possess the ability to cause severe health issues to humans and animals. The flavonol, kaempferide (KF), exhibits multiple pharmacological potentials. Therefore, this investigation was designed to estimate the mitigative effect of KF against Cd instigated hepatic damage in rats. 24 albino rats (male) were kept in 4 different groups. The group-1 was designed as untreated/control group, group-2 was orally provided with Cd (5 mg/kg), group-3 was orally co-administrated with Cd (5 mg/kg) along with KF (20 mg/kg) and group-4 was supplemented with KF (20 mg/kg) during 30 days of trial. Cd administration significantly escalated ALT, ALP as well as AST levels. A substantial decline in SOD, GST, POD, CAT, GSR activities and GSH content was observed due to Cd exposure along with an elevation in TBARS and H2O2 levels. Moreover, Cd administration elevated NF-kB, IL-6, TNF-α as well as IL-1β levels in addition to the activity of COX-2. Furthermore, the levels of Bax, Caspase-9 as well as Caspase-3 were escalated, besides the level of Bcl-2 was decreased after Cd exposure. A significant increase in histopathological damages after Cd administration is a clear indication of liver damage. However, co-treatment of KF with Cd potential recovered all the damages and significantly reduced the biochemical and histological variations in rat liver. Overall results indicated that KF has efficient anti-oxidant properties, which mitigated Cd instigated hepatic damage in rats.

Nanoparticles are widely used in the pharmaceutical, agriculture, and food processing industries. In this study, we have synthesized green lead nanoparticles (gPbNPs) by using an extract of Ziziphus spina-christi leaves and determined their cytotoxic and apoptotic effect on the human breast cancer MDA-MB-231 cell line. gPbNPs were characterized by using X-ray diffraction (XRD), energy dispersive X-ray (EDX) scanning electron microscope (SEM), and transmission electron microscope (TEM). The toxicity of gPbNPs was determined on the MDA-MB-231 cell line using MTT and NRU assays and as a result cell viability was reduced in a concentration-dependent manner. MDA-MB-231 cells were more sensitive at the highest concentration of gPbNPs exposure. In this experiment, we observed the production of intracellular ROS in cells, and induction of caspase 3/7 was higher in cells at 42 µg/ml of gPbNPs. Moreover, the Bax gene was upregulated and the Bcl-2 gene was downregulated and increased caspase 3/7 activity confirmed the apoptotic effect of gPbNPs in cells. Our observation showed that gPbNPs induced cell toxicity, increased generation of intracellular ROS, and gene expression of Bcl-2 and Bax in the MDA-MB-231 cell line. In conclusion, these findings demonstrated that gPbNPs executed toxic effects on the MDA-MB-231 cell line through activating caspase 3/7 activity.

Moringa oleifera is a nutrient-rich plant, also referred to as a miracle tree, and is commonly used in the preparation of functional foods including herbal biscuits. Despite having a wide range of biomolecules, M. oleifera has not been studied for its nutritional benefits in Nepal. To fill this gap, five different formulations of flower and leaf powder ratios of 11:4, 11.75:3.25, 12.5:2.5, 13.25:1.75, 14:1 named as A, B, C, D, E, and control formulations were tested for their sensory and chemical characteristics. The results showed that calcium content (115.73 mg/100 g) was higher in biscuits with a higher percentage of the leaf (11:4) while TPC was minimum. Further, biscuits containing a higher percentage of flower powder contained fewer tannins. The sensory analysis concluded that D was deemed the best in overall attributes by panelists upon statistical analysis, however formulations A and B were superior to other samples regarding the chemical properties. These findings confirm that there is a huge potential for improving herbal biscuits.

5-fluorouracil (5FU) is widely used to treat colorectal cancer (CC) and its main mechanisms of anticancer action are through generation of ROS which often result in inflammation. Here, we test the effect of Lycopene against 5FU in Caco2 cell line. Caco2 cells were exposed to 3 µg/ml of 5FU alone or with 60, 90, 120 µg/ml of lycopene. This was followed by assessment of cytotoxicity, oxidative stress, and gene expression of inflammatory genes. Our findings showed that Lycopene and 5FU co-exposure induced dose-dependent cytotoxic effect without compromising the membrane integrity based on the LDH assay. Lycopene also significantly enhanced 5FU-induced SOD activity and GSH level compared to control for all mixture concentrations (p

Gentamicin (GEN) is an extensively used aminoglycoside. Contrary to its antibacterial potential, it can induce oxidative stress in several organs, including kidney. Amentoflavone (AMN) is a biflavonoid with conspicuous pharmacological activities. The current study was held to estimate the curative efficacy of AMN to antagonize the nephrotoxic effects instigated by GEN. 48 albino rats were separated into four groups: control group, GEN administrated group (80 mgkg−1 intraperitoneally), GEN + AMN treated group (80 mgkg−1 + 40 mgkg−1) and only AMN administrated group (40 mgkg−1). Following 30 days of administration, results showed that GEN disturbed antioxidant enzymes i.e., glutathione (GSH), glutathione reductase (GSR), glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) activity, besides elevated malondialdehyde (MDA) along with reactive oxygen species (ROS) level. Besides this, level of inflammatory cytokines involving interleukin-6 (IL-6), nuclear factor-kappa B (NF-κB), interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α) & cyclo-oxygenase-2 (COX-2) were escalated. Furthermore, treatment with GEN enhanced the level of apoptotic proteins comprising of Bax, caspase-9 along with caspase-3 besides lessened the level of Bcl-2. In addition to this, GEN reduced the level of albumin, creatinine clearance & augmented the level of creatinine, urea, urobilinogen, urinary protein, kidney injury molecules-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) as well as instigated various histopathological damages. However, co-treated group (AMN + GEN) revoked abovementioned renal dysregulations instigated by GEN. Taken together, AMN could significantly counteract GEN-instigated nephrotoxic effects due to its antioxidant capabilities.

Chorein is variably expressed in different cancer cells. In various non-malignant cell types, this protein regulates cytoskeleton microstructure and signaling. However, the role of chorein in regulating the actin cytoskeleton in tumor cells remains elusive. Here, we investigated chorein expression in various breast tumor cells and the involvement of this protein in microfilament organization. We used laser scanning microscopy to analyze microfilaments architecture, Triton X-100 fractionation to quantify G and Total actin levels, and quantitative RT-PCR to assess chorein gene transcription. We show that in line with previous observations, the less differentiated MCF7 breast cancer cells exhibited the highest relative expression of chorein compared to MDA-MB231 and T47D cell lines. Contrastingly, in less differentiated ZF rhabdomyosarcoma cells expressing high chorein levels, silencing of this protein was followed by clear depolymerization of actin microfilaments as apparent from IF morphological analysis. Quantification of G- and F-actin levels by Triton X-100 fractionation that revealed a significant increase in this ratio fully supported this finding. These results disclose that chorein is highly expressed in less differentiated tumor cells. In addition, silencing of this protein induces significant structural disorganization of the actin network, providing clear evidence that chorein regulates microfilament cytoskeleton architecture in tumor cells of higher malignant potential.

The current study was designed to determine the curative potential of astragalin (AST) against polystyrene microplastics (PS-MPs) induced hepatic toxicity in rats. PS-MPs exposure decreased the expression of Nrf-2 and anti-oxidant enzymes, while increasing Keap-1 expression. The activities of glutathione-S-transferase, catalase, glutathione, glutathione peroxidase, superoxide dismutase, glutathione reductase and heme oxygenase-1 were decreased, besides the levels of malondialdehyde and reactive oxygen species were also increased following the exposure of PS-MPs. The intoxication of PS-MPs elevated aspartate aminotransferase, alanine transaminase, alkaline phosphatase levels, as well as cyclooxygenase-2 activity, interleukin-6, interleukin-1 beta, nuclear factor-kappa B and tumor necrosis factor-alpha levels were also escalated. Furthermore, Bcl-2 expression was down-regulated, while Bax and Caspase-3 expressions were upregulated following PS-MPs exposure. Histopathological assessment revealed substantial liver damages in PS-MPs treated rats. However, AST supplementation substantially recovered PS-MPs-induced damages and histological anomalies. Therefore, AST can be used as a curative agent to treat PS-MPs-prompted hepatotoxicity due to its anti-apoptotic, anti-inflammatory and anti-oxidant potentials.

Background The purpose of this study is to analyzed the involvement of chorein in microtubules organization of three types of malignant; rhabdomyosarcoma tumor cells (ZF), rhabdomyosarcoma cells (RH30), and rhabdomyosarcoma cells (RD). ZF are expressing high chorein levels. Previous studies revealed that chorein protein silencing in ZF tumor cells persuaded apoptotic response followed by cell death. In addition, in numerous malignant and non-malignant cells this protein regulates actin cytoskeleton structure and cellular signaling. However, the function of chorein protein in microtubular organization is yet to be established. Methods In a current research study, we analyzed the involvement of chorein in microtubules organization by using three types of malignant rhabdomyosarcoma cells. We have applied confocal laser-scanning microscopy to analyze microtubules structure and RT-PCR to examine cytoskeletal gene transcription. Results We report here that in rhabdomyosarcoma cells (RH30), chorein silencing induced disarrangement of microtubular network. This was documented by laser scanning microscopy and further quantified by FACS analysis. Interestingly and in agreement with previous reports, tubulin gene transcription in RH cells was unchanged upon silencing of chorein protein. Equally, confocal analysis showed minor disordered microtubules organization with evidently weakened staining in rhabdomyosarcoma cells (RD and ZF) after silencing of chorein protein. Conclusion These results disclose that chorein silencing induces considerable structural disorganization of tubulin network in RH30 human rhabdomyosarcoma tumor cells. Additional studies are now needed to establish the role of chorein in regulating cytoskeleton architecture in tumor cells.

Background: Bezoar (PB) is a rare, solidified form of undigested food commonly found in the gastrointestinal tract of porcupine (Hystrix brachyura). It is believed to be traditionally used to treat various diseases including different kinds of cancers in Malaysia. However, its active principles have not been found out yet. The purpose of this study was to investigate the anticancer property of PB extract as well as to identify the metabolites responsible for its anticancer effect through a widely acclaimed metabolomics approach. Methods: Initially, 25 PB extracts using various solvent ratios of methanol–water (100, 75, 50, 25, 0% v/v) were prepared in regard to metabolomics approach and subsequently the cytotoxicity of each extract was determined against (melanoma) A375 cell line. The metabolites profiling of the most potent extract was conducted using gas chromatography mass spectrometry (GC–MS) and in silico investigation was performed on Bcl-2 and cyclin/CDK1 complex protein. Results: The correlation of the bioactivity with GC–MS data produced an orthogonal partial least square (OPLS) model which pinpointed four putative active compounds namely (1) cholest-7-en-3-beta-ol,4,4-dimethyl-,acetate; (2) 4-androsten-4-ol-3,17-dione; (3) isolongifolol and (4) gallic acid. The in silico data suggested the binding score and binding mode of active metabolites with the amino acid residues of protein via hydrophobic interactions. Conclusion: This study is the first to report the identified anticancer compounds from PB extract and evaluate them using molecular docking. This further confirms and justifies its traditional usage as an alternative medicine for the treatment of cancer in Malaysia.

Introduction: Increased mortality owing to breast and lung cancer is an urgent global medical issue. Nanotherapy is one of the most widely used and recent procedures for combating cancer. Therefore, this study aimed to assess the beneficial effects of multi-walled carbon nanotubes (MWCNTs) to precisely target breast (MCF-7) and lung cancer (A549) cell lines. Multi-walled carbon nanomaterials are considered as a typical biocompatible nanomaterial that can be used in drug delivery without causing side effects. On the contrary, the metallic nanoparticles, even that of noble metals, are reported to have side effects that are still unavoidable.Methods: The MWCNTs were purified and stabilized using Arabic gum in an aqueous solution under ultrasonic radiation. Scanning and transmission electron microscopy (SEM and TEM, respectively) were employed to characterize the morphology of the MWCNTs, and elemental analysis was performed using SEM to determine their chemical composition.Results: The investigated MWCNTs had an average diameter of 10–12 nm and were mainly composed of 99.4% carbon and other trace elements. The Arabic gum emulsifying agent was found a powerful stabilizing agent for the investigated MWCNTs in aqueous solutions. The cytotoxic effect of the MWCNT/ Arabic gum colloidal solution on MCF-7 and A549 was evaluated by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays, and the expression of apoptosis-related genes was assessed using quantitative real-time polymerase chain reaction and a human apoptosis signaling antibody array. This analysis aimed to clarify additional pathways involved, including those mediated by interleukin-1, tumor necrosis factor-α, and ceramide signaling pathways enrichments. Concerning the inhibition of cell growth, the efficacy of MWCNT/Arabic gum IC50 of MCF-7 (48.23 μg/mL) was higher than IC50 of A549 (100.1 μg/mL). MWCNT/Arabic gum enhanced the mRNA expression of apoptosis-associated genes encoding P53, Bax, and Caspases (9, 8, and 3). Upregulation of the apoptotic signaling pathway in the MCF-7 cell lysates was observed before and after exposure to the MWCNT/Arabic gum colloidal solution.Conclusion: The physicochemical properties of MWCNT/Arabic gum exhibited remarkable apoptotic activity in breast and lung cancer cell lines. However, further in vivo investigations are recommended to clarify the other molecular aspects related to the use of MWCNT/Arabic gum.

Nanoparticles have shown promising potential for efficient drug delivery, circumventing biological interferences like immunological and renal clearance and mechanical and enzymatic destruction. However, a handful of research papers have questioned the biomedical use of metal-based nanoparticles like cadmium telluride quantum dots (CdTe-QDs) for their cytotoxic, genotoxic, and carcinogenic potential. Herein, we examined the effects of CdTe-QD NPs on gene expression profile of hepatocellular carcinoma (Huh-7) cell line. Huh-7 cells were treated with CdTe-QD NPs (10 μg/ml for 6, 12, and 24 hours, and 25 μg/ml for 6 and 12 hours), and transcriptomic analysis was performed using microarray to evaluate the global gene expression profile. Differential expressed genes (DEGs) were observed for both the doses (10 and 25 μg/ml) of CdTe-QD NPs at different time points. Gene ontology (GO) analysis revealed that genes involved in molecular function of cell cycle, organizational injury and abnormalities, cell death and survival, gene expression, cancer, organismal survival, and cellular development were differentially expressed. Overall, we have demonstrated differential expression of several genes, involved in maintaining cell survival, metabolism, and genome integrity. These findings were confirmed by RT-qPCR study for some canonical pathway genes signifying possible implication in NP toxicity-mediated cell survival and inhibition of cell death.

Colon cancer (CC) is a common form of cancer worldwide. According to growing incidence of cancer and little information about the possible protective role of Ivermectin (IVM) on colon cancer, this study aimed to investigate the chemoprotective role of IVM against colon cancer induced by Dimethylhydrazine (DMH) in Male Wistar Rats. Based on LD50, three doses of IVM (0.25, 0.5, and 1 mg/kg) were applied before assayingthe antioxidant status, apoptotic markers, and microscopic analysis. Our result showed that glutathione (GSH) level was significantly increased in low dose of IVM-treated rats. Hight levels of oxidative stress and tissue damage consumed GSH and catalase (CAT), and dismutase (SOD) as indicated by significant drop in the treated groups. mRNA levels of Bax and caspase-3 were upregulated in rats treated with the high dose. Contrastingly, the expression of Bcl-2 was significantly downregulated with high dose. Changes in genes expression proved that IVM triggered apoptosis in treated groups compared to untreated control group. Microscopic analysis showed that rats treated with DMH exhibited high development of colorectal tumor. After induction of colorectal tumor, medium and high dose of DMH induced reduction in medullary carcinoma with great incidence of lymphoid nodules and desmoplastic reaction. In conclusion, this study demonstrates the potential of IVM as an anticancer drug against colon cancer in male Wistar rats.

Abstract Background Data available support that ninety percent of male infertility cases are due to low sperm counts. There is a scarcity of data on the medicinal effects of cannabis on fertility. This study evaluated testicular function and sperm quality modulation with cannabis in rats. Methodology Twenty-five male Wistar rats were randomly grouped into five: A, B, C, and D, each group have 5 rats. A (control): 0.2 ml 2% DMSO, B (vitamin C): 90 mg/kg body weight, C, D, and E were administered: 5 mg/kg, 10 mg/kg and 20 mg/kg body weight of ethanolic leaf extract of cannabis (ELEC) respectively. The rats were sacrificed 24 h after the last day of the 60 day oral administrations. Flavonoids were the predominant phytochemical present in the extract while quercetin, kemferol, silyman and gallic acid were identified. Results The results showed a significant improvement (p

Objectives: Cuscuta reflexa is parasitic plant of subtropical and temperate areas, commonly named as amarbel or akasvel in India. Present study is to investigate the In-vivoanti-inflammatory potential of C. reflexa seed essential oil. Materials and methods: In this study the essential oil was hydro-distilled from dried seeds and analyzed for chemical profiling and anti-inflammatory activity. In –vivo activity was performed on mice inducing TPA as disease causing agent. Study of biochemical parameter and oxidative stress was performed by taking homogenate of ear pinna of mice. Results: Chemical analysis is done by GC and GC-MS study, we found β-Bisabolene and Hexahydro farnesyl acetone as the major component as 13.2 and 14.2% respectively along with cis-chrysanthenyl acetate, caryophyllene oxide, carotol, caryophyllene oxide. In-vitro activity of cell viability was assessed using RAW 264.7 macrophages, showed no reduction in viable cell in the processed culture. In-vivo it significantly reduces the inflammation by inhibiting pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α). Conclusions: Cuscuta reflexa seed essential oil was found effective in the management of inflammation by encountering the inflammatory mediators (cytokines).

Malaria is often characterized by a complicated disease course due to multifaceted intrinsic genetic factors of the host and the parasite. This study aimed to investigate the role of interleukin-27 ( IL-27 ) gene polymorphisms in Plasmodium falciparum malaria infection in a Saudi Arabian cohort. This case-control study obtained blood samples from 250 malaria patients with P. falciparum and 200 randomly identified healthy control subjects from the Malaria Center in the Jazan area. Malaria patients were grouped into three cohorts as follow: low (1000 parasites/µl of blood) parasitemia. The results show that the IL-27 variant rs181209 was significantly associated with malaria patients ( P = 0.026). Similarly, the homozygous GG genotype of rs26528 was also associated with risk of developing P. falciparum malaria ( P = 0.032). The minor allele C of variant rs181206 exhibited an association with low to moderate parasitemia ( P = 0.046). Furthermore, the rs181209 AA genotype was statistically significant in age group 1–5 years ( P = 0.049). In conclusion, this study suggests that variant rs181209 and rs26528 could be associated with the risk of malaria infection by P. falciparum in the population studied.

Environmental sustainability (ES) requires conducting business activities by causing the least harm to the environment. Care and caution must be exercised to see that natural resources are not depleted and that environmental assets are preserved for posterity. ES is a precondition for sustained economic growth, requiring integrated multi-disciplinary knowledge and decision-making. Using structural equation modelling (SEM), the study examined a few antecedents of ES. The antecedent variables examined include environmental attitude (EnA), New environmental paradigm (NEP), and pro-environmental behaviour (PB). The data for the study was collected online from 453 gainfully employed samples from Saudi Arabia using three structured questionnaires. All the questionnaires had robust reliability and validity. SEM analysis revealed a significant positive relationship between the identified variables ad ES. The study has various theoretical and practical implications, which are discussed. It is expected that the present study will motivate social scientists to involve in further examinations of similar nature.

Abstract Croton macrostachyus is an important plant in traditional African medicine, widely utilized to treat a variety of diseases. In Kenya, HIV-infected patients use leaf and root decoctions of the plant as a cure for cough, back pain, bleeding, skin diseases, warts, pneumonia, and wounds. This study aimed to evaluate the anti-HIV activities and cytotoxic effects of extracts and chemical constituents isolated from C. macrostachyus. In our previous study we demonstrated that the hexane, CH2Cl2, ethyl acetate and methanol soluble fractions of a 1:1 v/v/ CH2Cl2/MeOH crude extracts of the leaves and stem bark of C. macrostachyus exhibited potent anti-HIV activities against HIV-1 with IC50 values ranging from 0.02–8.1 μg/mL and cytotoxicity effects against MT-4 cells ranging from IC50 = 0.58–174 μg/mL. Hence, hexane soluble extract of 1:1 v/v/ CH2Cl2/MeOH crude extract of the leaves of C. macrostachyus, that was more potent against HIV-1 at IC50 = 0.02 μg/mL was subjected to column chromatography leading to the isolation of 2-methoxy benzyl benzoate (1), lupenone (2), lupeol acetate (3), betulin (4), lupeol (5), sitosterol (6) and stigmasterol (7). Lupenone (2), lupeol acetate (3) and betulin (4) exhibited anti-HIV-1 inhibition at IC50 = 4.7 nM, 4.3 and 4.5 μg/mL respectively. The results obtained from this study support the potential of C. macrostachyus, as a source of anti-HIV constituents.

Coronavirus (covid-19) infection is considered to be deadliest ever pandemic experienced by the human being. It has very badly affected the socio-economic health of human and stuck the scientific community to think and rethink about its complete eradication. But due to no effective treatment or unavailability of vaccine the health professional could not show any significant improvement to control the pandemic. The situation needs newer molecule, vaccine or effective treatment to control covid-19 infection. Different target in viruses has been explored and proteases enzymes were found to be therapeutically effective target for the design of potential anti-covid-19 molecule as it plays the vital role in viral replication and assembly. Structure-based drug design was employed to discover the small molecule of anti-covid-19. Here we considered the small library of naturally occurring polyphenolic compounds and molecular docking, Molecular dynamics (MD) simulations, free binding energy calculation and in-silico ADME calculations to identify the newer HITs. Based upon their score the two molecules were identified as promising candidate. The docking scores were found to be −7.643 and −7.065 for the HIT1 and HIT-2 respectively. In MD simulations study the RMSD values were found to be 4.3 Å & 4.9 Å respectively. To validate these results MM-GBSA was performed and their binding free energies were computationally determined. The prime energy values of identified HITs (−13412.45 & −13441.8 kJ/mole) were found to be very close proximity to reference molecule (−13493.05 kJ/mole). Then in-silico ADME calculations were performed to calculate the drug likeliness identified HITs. BY considering all the values comparative to reference molecule and obtained in-silico pharmacokinetic properties of identified HITs we can suggest that HIT-1 and HIT-2 would be the most promising molecules that can inhibit the main protease enzyme of covid-19. These two molecules would become the potential drug candidate for the treatment of covid-19 infections.

Objectives: Diabetes mellitus (DtM) is a collection of recurrent metabolic abnormalities that are generally assessed by persistent hyperglycemia. This condition occurs when the insulin released from the pancreatic cells get destroyed and produce little or no insulin. In traditional Chinese medicine, Abelmoschus esculentus (AS) is used for the treatment for type 1 diabetes. This study aims to mitigate type 1 DtM caused by the administration of streptozotocin (STZ). Methods: Diabetes was produced in each of the Wistar rats by administering a single shot administration of STZ intraperitoneally. The rats were split into five groups. Group1 and 2 were normal control and diabetic control group. Groups 3, 4, and 5 were received okra mucilage extract and okra seed crude extract at a dosage of 150 mg/kg, 200 mg/kg, and 200 ml/kg. After 4 weeks animals were sacrificed and blood was collected through cardiac puncture and liver and kidney were dissected for further biochemical as well as histopathological examinations. Result: The FBG, %HbA1c, lipid profile, liver function test, oxidative stress, and histopathology investigation were analyzed. Our result showed a significant difference between different groups in each parameter. Our study revealed that okra mucilage extract has advantage over okra seed crude extract significantly. Conclusion: The extract of AS has an antidiabetic activity and contributes to the overall reduction in BG levels. Its properties can be a remedy to manage DtM. Based on the results of the tests, it was determined that a solid oral formulation might be made using okra-derived mucilage crude extract and aqueous seed extract as a pharmaceutical excipient.

Cancer is emerging as one of the most significant challenges to the human health. Ivermectin (IVM) is one of the most effective drugs in veterinary and human medicine. The purpose of this study was to evaluate the potential preventative effect of IVM against cytotoxicity induced by dimethylhydrazine (DMH) in Male Wistar rats. Three concentrations of IVM (0.25, 0.5 and 1 mg/kg) were utilized in this study. Liver function enzymes, inflammatory markers and histopathological alterations in liver and kidney tissues were investigated. Obtained data showed that the combination of DMH with each concentration of IVM increased the activity of liver enzymes (ALT, ALP, AST, and GGT) compared to control and DMH alone. RT-PCR findings showed upregulation in the level of INF-γ, IL-6, IL-1β, Cox1, and Cox2 genes compared to control. In contrast, IL-6 gene was down-regulated. The levels of genes expression were down-regulated with combined DMH with medium and high concentrations compared to DMH alone. Microscopic analysis demonstrated histological alterations in the liver and kidney of rats treated with DMH. Combinations of DMH either with medium or high concentration resulted in less pathological features in both liver and kidney tissues. In conclusion, this study showed that IVM mitigated the toxic effects of DMH on the liver and kidney of male Wistar rats.

This paper aims to solve general fractional Lane-Emden-Fowler differential equations using the Haar wavelet collocation method. This method transforms the fractional differential equation into a nonlinear system of equations, which is further solved for Haar coefficients using Newton’s method. We have constructed the higher-order Lane-Emden-Fowler equations. We have also discussed the convergence rate and stability analysis of our technique. We have explained the applications and numerically simulated the examples graphically and in tabular format to elaborate on the accuracy and efficiency of this approach.

The deadliest recent pandemic outbreak of COVID-19 disease has severely damaged the socio-economic health of the people globally. Due to unavailability of any effective vaccine or treatment the human beings are still struggling to overcome the pandemic condition. In an attempt to discover anti-COVID molecule, we used in-silico approach and reported 160 natural polyphenols to identify the most promising druggable HITs that can further used for drug discovery process. The co-crystallized structure COVID protease enzyme (PDB id 6LU7) was used. HTVS, MD simulation, binding energy calculations and in-silico ADME calculation were done and analyzed. Depending upon the scores three compounds galangin, nalsudaldain and rhamnezine were identified and the docking score were found to be −7.704, −6.51, −4.212 respectively. These docked complexes were further subjected to MD simulation runs over a 100 ns time and the RMSD and RMSF values were determined. The RMSD values of three compounds were found to be 2.9 Å, 7.6 Å & 9.5 Å respectively and the lowest RMSF values suggested the steady stability of ligand–protein complexes. The binding free energies (ΔG) of compounds with protein were found to be −49.8, −56.45, −62.87 kJ/mole. Moreover, in-silico ADME calculations indicated the drug likeliness properties of these molecules. By considering all these in-silico results the identified HITs would be the most probable anti-COVID drug molecules that can be further taken in wet lab and can act as lead for development of newer inhibitor of COVID-19 main protease enzyme.

Objectives: The present search aimed to investigate the effect of dandelion seeds extract to reduce hypercholesterolemia and its hazardous effects on liver. Methods: Forty male albino mice were divided into 4 groups, 10 mice per each, the first was the untreated control, the second treated with 400 mg/kg dandelion seed extract, the third treated with 5 mg/kg of cholesterol powder dissolved in oil and the fourth treated with cholesterol and dandelion extract. Results: It was showed that dandelion seeds extract reduced the weight of the mice. Cholesterol treatment resulted in highly significant increase of liver enzymes activities, total cholesterol, how-density lipoprotein (HDL) and low-density lipoprotein (LDL) of serum besides to pathological changes as steatosis, inflammation, fibrosis and high pathological score in the liver. Dandelion seeds extraction treatment resulted in marked decrease of liver enzymes activities total cholesterol, HDL and LDL of serum, in addition to hepatic tissue improvement with less steatosis, inflammation, fibrosis and lowered pathological score. Conclusion: Dandelion seeds extract could reduce hypercholesterolemia in swiss albino mice.

Alpha-amylase is widely exploited as a drug target for preventing postprandial hyperglycemia in diabetes and other metabolic diseases. Inhibition of this enzyme by plant-derived pregnanes is not fully understood. Herein, we used in vitro, in silico, and in vivo studies to provide further insights into the alpha-amylase inhibitory potential of selected pregnane-rich chromatographic fractions and four steroidal pregnane phytochemicals (SPPs), viz: marsectohexol (P1), 3-O-[6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→14)-β-D-oleandropyranosyl]-11,12-di-O-tigloyl-17β-marsdenin (P2), 3-O-[6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl]-17β-marsdenin (P3), and 3-O-[6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-canaropyranosyl]-17β-marsdenin (P4) derived from Gongronema latifolium Benth. The results revealed that the SPPs source pregnane-rich chromatographic fractions and the SPPs (P1–P4) exhibited inhibitory potential against porcine pancreatic alpha-amylase in vitro. Compounds P1 and P2 with IC50 values 10.01 and 12.10 µM, respectively, showed greater inhibitory potential than the reference acarbose (IC50 = 13.47 µM). Molecular docking analysis suggests that the SPPs had a strong binding affinity to porcine pancreatic alpha-amylase (PPA), human pancreatic alpha-amylase (HPA), and human salivary alpha-amylase (HSA), interacting with the key active site residues through an array of hydrophobic interactions and hydrogen bonds. The strong interactions of the SPPs with Glu233 and Asp300 residues may disrupt their roles in the acid-base catalytic mechanism and proper orientation of the polymeric substrates, respectively. The interactions with human pancreatic amylase were maintained in a dynamic environment as indicated by the root mean square deviation, radius of gyration, surface accessible surface area, and number of hydrogen bonds computed from the trajectories obtained from a 100-ns molecular dynamics simulation. Key loop regions of HPA that contribute to substrate binding exhibited flexibility and interaction potential toward the compounds as indicated by the root mean square fluctuation. Furthermore, P1 significantly reduced blood glucose levels and area under the curve in albino rats which were orally challenged with starch. Therefore, Gongronema latifolium and its constituent SPPs may be exploited as inhibitors of pancreatic alpha-amylase as an oral policy for impeding postprandial blood glucose rise.

The cell-traversal protein for ookinetes and sporozoites (CelTOS), expressed on the surface of ookinetes and sporozoitesin Plasmodium species, is a promising malaria vaccine candidate. CelTOS is essential for parasite invasion into mosquito midgut and human hepatocytes, thereby contributing to malaria transmission and disease pathogenesis. This study explores the genetic diversity, polymorphisms, haplotypes, natural selection, phylogenetic analysis, and epitope prediction in the full-length Plasmodium knowlesi CelTOS gene in clinical samples from Sarawak, Malaysian Borneo, and long-term laboratory strains from Peninsular Malaysia and the Philippines. Our analysis revealed a high level of genetic variation in the PkCelTOS gene, with a nucleotide diversity of π ~ 0.021, which was skewed towards the 3’ end of the gene. This level of diversity is double that observed in PfCelTOS and 20 times that observed in PvCelTOS from worldwide clinical samples. Tests of natural selection revealed evidence for positive selection within clinical samples. Phylogenetic analysis of the amino acid sequence of PkCelTOS revealed the presence of two distinct groups, although no geographical clustering was observed. Epitope prediction analysis identified two potential epitopes (96AQLKATA102 and 124TIKPPRIKED133) using the IEDB server and one epitope (125IKPPRIKED133) by Bcepred server on the C’ terminal region of PkCelTOS protein. Both the servers predicted a common epitope region of nine amino acid length (IKPPRIKED) peptide, which can be studied in the future as a potential candidate for vaccine development. These findings shed light on the genetic diversity, polymorphism, haplotypes, and natural selection within PkCelTOS in clinical samples and provide insights about its future prospects as a potential candidate for P. knowlesi malaria vaccine development.

Background and Objectives: Colon cancer (CC) is the second most common cancer in Saudi Arabia, and the number of new cases is expected to increase by 40% by 2040. Sixty percent of patients with CC are diagnosed in the late stage, causing a reduced survival rate. Thus, identifying a new biomarker could contribute to diagnosing CC in the early stages, leading to delivering better therapy and increasing the survival rate. Materials and Methods: HSPB6 expression was investigated in extracted RNA taken from 10 patients with CC and their adjacent normal tissues, as well as in DMH-induced CC and a colon treated with saline taken from a male Wistar rat. Additionally, the DNA of the LoVo and Caco-2 cell lines was collected, and bisulfite was converted to measure the DNA methylation level. This was followed by applying 5-aza-2′-deoxycytidine (AZA) to the LoVo and Caco-2 cell lines for 72 h to see the effect of DNA methylation on HSPB6 expression. Finally, the GeneMANIA database was used to find the interacted genes at transcriptional and translational levels with HSPB6. Results: We found that the expression of HSPB6 was downregulated in 10 CC tissues compared to their adjacent normal colon tissues, as well as in the in vivo study, where its expression was lower in the colon treated with the DMH agent compared to the colon treated with saline. This suggests the possible role of HSPB6 in tumor progression. Moreover, HSPB6 was methylated in two CC cell lines (LoVo and Caco-2), and demethylation with AZA elevated its expression, implying a mechanistic association between DNA methylation and HSPB6 expression. Conclusions: Our findings indicate that HSPB6 is adversely expressed with tumor progression, and its expression may be controlled by DNA methylation. Thus, HSPB6 could be a good biomarker employed in the CC diagnostic process.

According to WHO reports, the emergence of antibiotic resistance together with limited discovery of newer and effective anticancer and antimicrobial chemotherapeutics remained of utmost concern to human health. In addition, the poor solubility, stability, and side effects that lead to inefficiency of current anticancer and antimicrobial therapy encouraged research into new strategies to combat such resilient disease. Various metal nanoparticles (MNPs) such as gold (Au), silver (Ag), and others synthesized from natural or chemical sources have displayed potential biological properties against a wide range of microbial infections caused by multi-drug resistant bacteria. Remarkably, gold nanoparticles (Au-NPs) have gained particular concern, due to their biocompatibility, ease of surface functionalization, and their optical properties. Several studies have been carried out to investigate the antibacterial potentials of Au-NPs and findings showed that these NPs triggers microbial and cancer cell damage as a result of oxidative stress, membrane and DNA damage. In this review, we present a concise description of a broad update on Au-NPs isolated from natural and chemical sources that render it application in biomedical research as therapeutic agents. The review focuses mainly on the anticancer and antimicrobial activities of Au-NPs in conjunction with microorganism being prompted by different biocompatible origin and its future prospects these infectious systems. Finally, we summarize new possibilities for Au-NPs-based biochemical systems as an effective medical nanotechnology based therapeutic.

Cancer is one of the leading health problems worldwide with hepatic cancer being one of the most common cancers. To date, a number of anti-cancer agents have been employed for chemotherapeutic purposes one of which includes chlorpropamide (CP). Because of the serious side effect of CP, this study aims to investigate the potential protective effect of coenzyme-10 (CoQ10) and piperine (PIP) against cytotoxicity induced by CP in HuH-7 cell line. Based on IC50, 10, 12, 10, and 12 µg/ml of CP, PIP, CoQ10, PIP + CoQ10 were selected for further investigations. MTT and NRU assays results showed the combinations of CP + PIP, CP + CoQ10, CP + PIP + CoQ10 demonstrated a potential cytotoxic effect on HuH-7 cells. Also, these drug combinations induced apoptosis and relative migration rate compared with CP as evaluated by TUNEL and wound healing assays respectively. Furthermore, mitochondrial membrane potential (MMP) indicated the three drug combinations improved the mitochondrial membrane permeability in HuH-7 cells. Finally, upregulation of bcl-2, caspase-3 caspase-8, caspase-9 and p53 genes in HuH-7 cells were observed in the drug combination treatments compared to CP alone, confirming the positive effect of PIP and CoQ10 when combined with CP. In conclusion, current results showed that PIP and CoQ10 have anti-cancerous properties and may be a useful resource for effective remedies in the treatment of liver cancer.

This trial assessed the efficacy of a commercial essential oil (EO) product on the immune response to vaccination against Newcastle disease (ND) and subsequent challenge with virulent ND virus genotype VII (vNDv genotype VII) by using the following experimental groups of broiler chickens (Each group had 21 birds with 3 replicates in each, n = 7): NC (negative control), PC (positive control), VC (vaccinated), and VTC (vaccinated and treated with EOs). Moreover, in a trial to study the effect of EOs on vNDv genotype VII in vivo as a preventive or therapeutic measure, 2 additional ND-vaccinated groups were used (PRV: medicated 1 D before vNDv challenge for 5 D; and TTT: medicated 2 D after vNDv challenge for 5 D). In addition, the immune-modulatory effect of EOs on the avian influenza (AI), infectious bronchitis (IB), and infectious bursal disease (IBD) vaccines was assessed through the serological response. The use of EOs along with administration of ND vaccines (VTC) revealed a lower mortality rate (42.86%), clinical signs, and postmortem lesion score (11) than ND vaccines alone (VC) (52.28% mortality and score 15), in addition to lower hemagglutination inhibition (P < 0.05) (6.5 ± 0.46) and viral shedding (10 log 2.28 ± 0.24) titres 1 wk after challenge in comparison with VC (8.63 ± 0.65 and 10 log 3.29 ± 0.72, respectively). Nevertheless, the EOs mixture (VTC) (1952 ± 28.82) did not significantly (P > 0.05) improve growth performance compared with the nontreated birds (NC and VC) (1970 ± 19.56 and 1904 ± 38.66). EOs showed an antiviral effect on vNDv in vivo (in chickens) as a preventive measure (PRV) as well as some therapeutic effect (TTT) through decreasing the viral shedding titres (loNC0), mortality rate, and severity of clinical signs and postmortem lesions, in addition to serum malondialdhyde level. Regarding the other viruses, the EOs mixture did not improve the immune response to the AI and IB vaccines but significantly (P < 0.05) increased the ELISA antibody titre for IBD virus at the 28th D of age (2,108 ± 341.05). The studied EOs mixture showed an immune-stimulating response to ND and IBD vaccines, antiviral effect against ND virus, especially if administered before the challenge; however, it did not have a growth-promoting effect.

Background: To provide better management of Fournier’s gangrene, mortality-associated comorbidities and common etiologies were identified. Methods: A systematic search was conducted using 12 databases, followed by meticulous screening to select relevant articles. Meta-analysis and meta-regression (for possible cofounders) were both done for all possible outcomes. Results: Out of 1186 reports screened, 38 studies were finally included in the systematic review and meta-analysis. A higher risk of mortality was detected in patients with diabetes, heart disease, renal failure, and kidney disease, with risk ratios (RR) and 95% confidence intervals (95% CI) of 0.72 (0.59–0.89), 0.39 (0.24–0.62), 0.41 (0.27–0.63), and 0.34 (95% CI 0.16–0.73), respectively. However, there was no association between mortality rates and comorbid hypertension, lung disease, liver disease, or malignant disease (p > 0.05). The highest mortality rates were due to sepsis (76%) and multiple organ failure (66%), followed by respiratory (19.4%), renal (18%), cardiovascular (15.7%), and hepatic (5%) mortality. Conclusions: Modifications to the Fournier’s Gangrene Severity Index (FGSI) are recommended, in order to include comorbidities as an important prognostic tool for FG mortality. Close monitoring of the patients, with special interest given to the main causes of mortality, is an essential element of the management process. Keywords: Fournier’s gangrene, Mortality, Systematic review

The emerged COVID-19 (SARS corona virus) pandemic leads to severe or fatal respiratory tract infections affecting millions of people worldwide since its outbreak. The situation needs the newer molecule to control the infections as the pandemic had very badly affected the health and socioeconomic conditions of human being. CoV-2 main protease is considered to be key enzyme by targeting which we can design or develop the drug candidate. The active fitting and binding of any molecule depends upon the shape and electrostatic properties of ligand complementary to the receptor site. In this study ZINC13 database, a drug like subset (13,195,609 molecules) was subjected to shape and electrostic based virtual screening (VROCS & EON software) and followed by molecular modelling studies using docking and molecular dynamics simulation. Further the drug ability of identified candidate was predicted by the SiteMap analysis. The best shape and electrostatic similarities were observed between ZINC19973962 and reference molecule. The Tamintoshape and Tanimotoelectrostatic was found to be 0.667 and 0.022 respectively. The molecule also displayed the identical binding pattern with docking score −7.964 and this interaction was further validated by the molecular dynamics simulations. The RMSD & RMSF values were found to be 1.5 Å and1.8 Å respectively suggesting the stability of complex and very low fluctuation in ligand–protein complex over the entire MD simulation run. SiteMap analysis showed the identical Dscore of reference and identified HIT that indicated the molecule ZINC19973962 would be the promising druggable candidate against COVID main protease enzyme and can be used as lead molecule for the development of anti-COVID molecule.

Ethnopharmacological Relevance: The management of diabetes over the years has involved the use of herbal plants, which are now attracting interest. We assessed the antidiabetic properties of aqueous extract of C. purpureus shoots (AECPS) and the mechanism of action on pancreatic ß-cell dysfunction.Methods: This study was conducted using Thirty-six 36) male Wistar rats. The animals were divided into six equal groups (n = 6) and treatment was performed over 14 days. To induce diabetes in the rats, a single dose of 65 mg/kg body weight of alloxan was administered intraperitoneal along with 5% glucose. HPLC analysis was carried out to identified potential compounds in the extract. In vitro tests α-amylase, and α-glucosidase were analyzed. Body weight and fasting blood glucose (FBG) were measured. Biochemical parameters, such as serum insulin, liver glycogen, hexokinase, glucose-6-phosphate (G6P), fructose-1,6-bisphosphatase (F-1,6-BP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-ĸB), were analyzed. Additionally, mRNA expressions of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), B-cell lymphoma 2 (Bcl-2), and proliferating cell nuclear antigen (PCNA) were each evaluated.Results: This in vitro study showed inhibitory potency of Cenchrus purpureus extract (AECPS) as compared with the positive controls. AECPS showed a gradual decrease in alloxan-induced increases in FBG, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL-c), G6P, F-1,6-BP, malondialdehyde (MDA), IL-6, TNF-α, and NF-ĸB and increased alloxan-induced decreases in liver glycogen, hexokinase, and high density lipoprotein (HDL-c). The diabetic control group exhibited pancreatic dysfunction as evidenced by the reduction in serum insulin, homeostasis model assessment of ß-cell function (HOMA-β), expressions of PI3K/AKT, Bcl-2, and PCNA combined with an elevation in homeostatic model assessment of insulin resistance (HOMA-IR). High performance liquid chromatography (HPLC) revealed 3-O-rutinoside, ellagic acid, catechin, rutin, and kaempferol in AECPS.Conclusion: AECPS showed efficient ameliorative actions against alloxan-induced pancreatic dysfunction, oxidative stress suppression as well as, inflammation, and apoptosis via the activation of PI3K/AKT signaling pathways.

In this study, nitrogen-nitrogen bonds containing compounds such as hydrazine derivatives are examined. There are relatively few hydrazine molecules in nature, but some have been isolated from plants, marine organisms and microorganisms. Thus, hydrazine molecules are widely used in the manufacture of synthetic catalysts, agriculture chemicals, pesticides, and also cause irreversible pollution to air, water, and soil. Hydrazine compounds were evaluated via larvicidal profile in a stagnant water system. According to the above observation, new 1H-pyrazolo[3,4-b]pyridin-3(2H)-one derivatives can be synthesized via catalyst free green chemistry approach. A range of FT-IR spectroscopic measures, 1H and 13C NMR, as well as mass spectra, were used to characterize the compounds (2a-e). The compound 2e was more potent (95,6% mortality, LD50: 20.1 µg/ mL) against Culex quinquefasciatus than natural pyrazolidine derivatives. Therefore, the objective of this study, prospered with a few of the pyrzolopyridine hydrazine models, which are demonstrated to be low toxic environmentally safe and high potential larvicidal profile.