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Background: Chewing Khat (Catha edulis) releases cathine and cathinone, which may reduce appetite via an unknown mechanism. This study investigated the peripheral and central effects of fresh leaves and buds of Catha edulis water extract (CEWE) on appetite biomarkers, gene expression, and body weight, using in vivo, ex vivo, and in silico models. Methods: Rats of both sexes were orally administered CEWE at different doses and durations in three different experiments. Liquid chromatography-mass spectroscopy (LC-MS)-MS was used to detect cathinone and cathine in the murine blood. The effect of Khat on serotonin receptors was studied in isolated rat fundus samples. Docking of the two Khat ligands was performed on G (The 5-hydroxytryptamine-type 2C receptor (5-HT2C) in an agonist-bound active conformation) and H (5-HT2C in an antagonist-bound inactive conformation) proteins to determine which ligands are most likely to act as agonists or antagonists. Results: Significant differences (P < 0.05) in body weight were observed between the CEWE-treated groups and the controls over eight weeks. However, the plasma leptin and ghrelin levels did not change significantly (P > 0.05). The expression of the ghrelin and leptin genes was also unaffected, but the expression of the 5-hydroxytryptamine (5-HT) gene decreased (P < 0.05) with CEWE treatment. CEWE antagonizes 5-HT receptors in isolated rat fundus samples. Docking findings indicated that the khat ligands bound to 5-HT2C receptors. Cathine and cathinone levels in rat plasma were measured. Conclusion: Khat extract may suppress appetite by antagonizing the 5-HT receptors. Further research is required to understand its mechanism and potential applications. [ABSTRACT FROM AUTHOR]

The project aimed to conduct an up-to-date and comprehensive bibliometric analysis of robotic surgery to provide a detailed and holistic understanding of the field. Three strategies were employed in the data analysis i.e. search terms were explored in (A) the title, abstract, and keywords and (B) only in the title of the documents. In 3rd part we analyzed the top 100 most cited papers. Vosviewer and R Studio were utilized for detailed bibliometric and network analyses. Strategy one identified 38,469 publications, and strategy two identified 6451 publications from 2001 to 2023. The top authors, universities, countries, sponsors, and sources based on the number of publications were identified for both strategies. The top 100 most cited papers were analyzed, providing the annual number of publications and various citation metrics. Top authors (by number of publications, total citations, h-index, g-index, and m-index), universities, and countries within these highly cited papers, along with their co-authorship networks and dynamics, were examined. Co-words analysis of the top 100 most cited papers revealed the primary focus of these documents across 25 categories. This comprehensive bibliometric analysis of robotic surgery highlighted significant contributions and collaborations in the field, emphasizing the importance of global and collaborative efforts in advancing robotic surgery research. [ABSTRACT FROM AUTHOR]

Aim: To develop and characterize doxorubicin-loaded sodium selenite nanoparticles (SSNP-DOX) and their surface attachment with cetuximab (mAb-SSNP-DOX). Methods: SSNP-DOX was formulated by gelation and then conjugated with cetuximab to form mAb-SSNP-DOX. Characterization included DLS, SEM, TEM, DSC, Raman spectroscopy and XRD. In vitro, the kinetics of doxorubicin release and cytotoxicity in MCF-7 breast cancer cells were investigated. Results: The zeta potential for SSNP-DOX and mAb-SSNP-DOX was -14.4 ± 10.1 mV and -27.5 ± 7.28 mV, with particle sizes of 181.3 nm and 227.5 nm, respectively. The formulation intensity was 89.7% for SSNP-DOX and 100% for mAb-SSNP-DOX, with PDI values of 0.419 and 0.251, respectively. SEM and TEM showed that mAb-SSNP-DOX was smooth and spherical. The DSC analysis revealed exothermic peaks at 102.44°C for SSNP-DOX and 144.21°C for mAb-SSNP-DOX, along with endothermic peaks at 269.19°C and 241.6°C, respectively. Raman spectroscopy showed a higher intensity for mAb-SSNP-DOX. The XRD study showed different peaks for each formulation. Both followed zero order kinetics for doxorubicin release. Cytotoxicity studies showed significant effects and high apoptosis in MCF-7 cells for both formulations. Conclusion: The mAb-SSNP-DOX showed promising properties, more effective doxorubicin release and higher cytotoxicity against breast cancer cells compared with SSNP-DOX. Article highlights Breast cancer Breast cancer is a significant cause of morbidity and mortality worldwide and is characterized by high heterogeneity and treatment resistance. MCF-7 cells are a commonly used human breast cancer cell line in research and a model for studying the efficacy of therapeutic interventions. Nanoparticle drug delivery system Drug delivery systems in the form of nanoparticles improve drugs' therapeutic efficacy and stability while minimizing unwanted side effects by enabling precise delivery to cancer cells. Targeted nanoparticle drug delivery systems, such as those incorporating monoclonal antibodies, further improve treatment outcomes by selectively targeting cancer cells and causing less damage to healthy tissue. Targeted breast cancer treatment The study focused on developing injectable nanoparticle formulations, SSNP-DOX and mAb-SSNP-DOX, which effectively target MCF-7 breast cancer cells. Combining cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), with SSNP-DOX improved the specificity and efficacy of the treatment. Characterization & physicochemical stability The nanoparticle formulations were comprehensively characterized using dynamic light scattering (DLS), differential scanning calorimetry (DSC), Raman spectroscopy, x-ray diffraction (XRD) and nuclear magnetic resonance spectroscopy (NMR). These techniques confirmed the formulations' stability and uniformity, ensuring their suitability for targeted drug delivery. In vitro performance & enhanced efficacy The release profiles of doxorubicin from SSNP-DOX and mAb-SSNP-DOX showed sustained drug release over a prolonged period. In vitro, cytotoxicity studies showed that both formulations effectively suppressed the growth of MCF-7 breast cancer cells. Of the two, mAb-SSNP-DOX was the superior formulation, performing better on all parameters tested. Target specificity & overcoming drug resistance mAb-SSNP-DOX showed increased specificity in targeting breast cancer cells due to cetuximab. This combination of nanoparticles with cetuximab represents a promising approach to overcoming drug resistance in the treatment of breast cancer, offering improved efficacy and targeting of breast cancer cells. Future directions Future research should focus on optimizing these formulations, investigating the underlying molecular mechanisms and conducting extensive in vivo studies to validate the therapeutic potential of mAb-SSNP-DOXstance and conducting extensive in vivo studies to validate these findings. [ABSTRACT FROM AUTHOR]

Background: Castanea sativa Mill. is important for ecosystems and societies. Its rich historical and cultural significance, remarkable ecological contributions, and diverse applications have inspired scientific research. This comprehensive review and conceptual mapping of chestnut research consolidates existing knowledge, identifies emerging trends, and highlights untapped potential to inform future investigations. First, the Scopus database was searched to retrieve all data-driven articles in English related to C. sativa published in English from 1951 to 2023. Second, the R language, Scopus Analytics, and VOSviewer were used to analyze the year of publication, authors, countries, affiliations, keywords, and citations. Finally, network analysis was performed to evaluate the hotspots and developmental trends of C. sativa. A total of 1889 research articles were recovered. Results: The articles showed an exponential progression, with a regression coefficient of 0.9435 (R2) and an annual growth rate of 6.28%. Italy (19.87%), Spain (15.56%), Portugal (13.39%), Turkey (6.92%), and Switzerland (5.17%) were the most prolific countries. C. sativa (798), sweet chestnut (54), cryphonectria parasitica (44), honey (38), phenolic compounds (35), chestnut blight (33) and antioxidant activity (31) are the keywords that occur the most frequently. The main research groups in the thematic map are "forest management," "Cryphonectria parasitica," "wood," "Spain" and "ethnobotany." Research on C. sativa has all the basic, motor, niche, and emerging or declining themes. Forest management, drought, Gnomoniopsis smithogilvyi, C. sativa shells, amino acids, honey, phenolic compounds, hydrolyzable tannins, antioxidant capacity, antioxidants, and extractives are trending topics. Conclusions: This bibliometric analysis highlights the importance of C. sativa research, revealing its ecological contributions, cultural significance, and diverse applications. Future studies should focus on forest management, drought resistance, and bioactive properties to ensure sustainable utilization. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have identified several risk factors for acute coronary syndrome (ACS). This study was intended to examine the potential risk of ACS associated with khat and tobacco use. Methods: A case-control study of 344 people (172 cases and 172 controls) was conducted at Prince Mohammed Bin Nasser Hospital in Jazan, Saudi Arabia, from April to September 2019. The cases and controls were matched for age (±5 years) and gender. Data were analyzed using descriptive, inferential, and modeling analyses. We utilized the adjusted odds ratio (AOR) to express the results. Results: The prevalence of ever khat chewing among all study participants was 29.1%, significantly higher for the cases with ACS than for the control group (43.6% vs 14.5%, p<0.001). Cigarette smokers accounted for 33.4% of the study participants, and 22.1% were ACS cases, which is a significantly higher percentage than the control group. The prevalence of smokeless tobacco was 20.3% among ACS cases and 14.5% among controls, with no statistically significant differences (p>0.05). In the final model, tobacco use was more likely to be reported among cases with myocardial infarction (MI) (AOR=4.58; 95% CI: 1.01–4.73, p<0.05) as was khat chewing (AOR=3.4; 95% CI: 1.55–7.46, p<0.05), after controlling for other traditional risk factors. Conclusions: Khat chewing was reported more by those who reported ACS. ACS cases were more likely to be frequent khat users with chewing sessions of five or more days per week. Regular tobacco use was also reported in those who reported ACS, and this increases with the amount of tobacco used. Implementing early intervention strategies can help mitigate the impact of khat chewing and smoking on the development of ACS. [ABSTRACT FROM AUTHOR]

Background and Aim: Colorectal cancer stands as a frequently occurring fatal disease for several decades and the use of nanoparticles has long been explored in cancer treatments. Engineering the size and shape to attain an optimal efficacy of the nanoparticles and using a specific plant resource to enhance its compatibility to other healthy cell is a propitious approach. The present study investigates the anti-cancer activity of CuO NP synthesized from Aegle marmelos leaf extract against human colorectal cancer. Materials and Methods: The CuO NPs (Nanoparticles) exhibited promising characteristics with UV and SEM-EDAX, its photochemical constituents were analyzed with FTIR, and the geometry of the synthesized nano-particles was studied using Zeta potential and particle size analyzer. The cell viability was scrutinized via trypan blue assay and further toxicity was determined by cell morphology and several in vitro analyses where the MTT assay presented that the 25 µg/mL of CuO NPs as the IC50 concentration. RESULTS: The nuclear fragmentation was studied by DAPI staining which resulted in increased fluorescence of the treated cells indicating the robust effect of the CuO NPs and the mitochondrial damage was monitored through MMP analysis with declining fluorescence. The most vital aspect of understanding cancer pathogenesis is oxidative stress which was evaluated by ROS, NO, and LPO with favorable outcome. Conclusion: The cell viability and ROS assay coalesce to suggest that CuO NPs indeed induce apoptosis and it is evident that Biogenically synthesized CuO NPs contain anti-proliferative potential and promotes apoptosis. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is a prominent contributor to cancer-related death among women residing in developed countries. The most of instances are discovered when the cancer has already developed, which results in dismal consequences. Surgery, chemotherapy, and radiation were the top priorities for first-line treatment in clinics. Traditional cancer treatments have a substantial risk of toxicity and cancer recurrence in females. Plant extracts can be utilized as an alternative to traditional chemotherapeutic drugs to solve these issues. According to recent research, plant extracts show anti-tumor, anti-cancer, and anti-proliferative effects on human tumor cell lines that have been cultivated, as well as an antiangiogenic impact. Aim: Eupatorin is a class of flavonoids isolated from various medicinal plants with various potent biological properties including anti-cancer, anti-inflammatory, and vasorelaxant actions. Materials and Methods: In the current investigation, the potential of Eupatorin as an anti-cancer agent for ovarian cancer was evaluated. In this study was determination of cytotoxicity using WST-1 assay, LDH release assay, and apoptotic cell death was detected through AO/EB dual staining, estimation of pro-apoptotic markers using ELISA method and in silico analysis. Results: The viability of PA-1 cells was reduced with an increased dosage of Eupatorin. The LDH level was increased with increased concentration of Eupatorin. The apoptosis markers levels were also increased when PA-1 cells were exposed to Eupatorin indicating apoptosis of cancer cells. The results showed that apoptosis was induced by Eupatorin in PA-1 cells by triggering the caspase pathway. In addition, the in silico experiment was done to examine the binding efficacy of Eupatorin with VEGF-A/VEGFR and found that Eupatorin can bind more persistently to VEGF-A/VEGFR than apratoxin thereby preventing angiogenesis. Conclusion: All these results suggest that Eupatorin can be used as a potent anti-cancer drug for ovarian cancer. [ABSTRACT FROM AUTHOR]

Vaccination is a groundbreaking approach in preventing and controlling infectious diseases. However, the effectiveness of vaccines can be greatly enhanced by the inclusion of adjuvants, which are substances that potentiate and modulate the immune response. This review is based on extensive searches in reputable databases such as Web of Science, PubMed, EMBASE, Scopus, and Google Scholar. The goal of this review is to provide a thorough analysis of the advances in the field of adjuvant research, to trace the evolution, and to understand the effects of the various adjuvants. Historically, alum was the pioneer in the field of adjuvants because it was the first to be approved for use in humans. It served as the foundation for subsequent research and innovation in the field. As science progressed, research shifted to identifying and exploiting the potential of newer adjuvants. One important area of interest is nano formulations. These advanced adjuvants have special properties that can be tailored to enhance the immune response to vaccines. The transition from traditional alum-based adjuvants to nano formulations is indicative of the dynamism and potential of vaccine research. Innovations in adjuvant research, particularly the development of nano formulations, are a promising step toward improving vaccine efficacy and safety. These advances have the potential to redefine the boundaries of vaccination and potentially expand the range of diseases that can be addressed with this approach. There is an optimistic view of the future in which improved vaccine formulations will contribute significantly to improving global health outcomes. [ABSTRACT FROM AUTHOR]

Kava is a herbal supplement and beverage made from the Piper methysticum plant, which is known for its recreational use as a mood enhancer, relaxation, as well as pain relief for centuries. Kava is widely used among alcoholics, but it is dangerous and potentially fatal. The objectives of this study were to examine the sub-acute toxicity effects of different doses of 70% kavalactone (KL) in rats by oral application, as well as to elucidate the mechanisms of toxicity alone and in combination with ethanol (EtOH). The most common side effects observed were abnormal breathing, ataxia, lethargy, loss of appetite, indigestion, and loss of coordination, especially in the 800 mg/kg bw, po bodyweight dosage of kava treatment group alone, and in combination with EtOH. In the sub-acute study, there were dose-related decreases in body weight, feed intake, and water consumption rates. Gross and histopathological findings revealed that the liver was abnormal in color, size, consistency, and the weight significantly increased at a dose of 800 mg/kg bw, po, with KL alone and a greater increase in combination with EtOH. Hepatocellular hypertrophy (HP) and necrosis with Kupffer cells hyperplasia were observed in the periacinar zone of all rats dosed with KL (800 mg/kg bw, po) alone, and extensive changes were observed in combination with EtOH. The periportal (Z1) and mid-zonal (Z2) areas of hepatocytes were less affected as compared to the periacinar zone. These results demonstrate that EtOH exacerbated the sedative and hypnotic activity of KL, and markedly increased toxicity. The histopathological results supported the clinical and biochemical findings and the severity of hepatic damage in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

A high increase witnessed in type II diabetes mellitus (T2DM) globally has increasingly posed a serious threat to global increases in liver cancer with the association between diabetes mellitus type II and the survival rate in liver cancer patients showing unstable findings. An increase in the development and progression of chronic liver disease from diabetes mellitus patients may be connected to cancer of the liver with several links such as Hepatitis B and C virus and heavy consumption of alcohol. The link between T2DM patients and liver cancer is centered on non-alcoholic fatty liver disease (NAFLD) which could be a serious threat globally if not clinically addressed. Several reports identified metformin treatment as linked to a lower risk of liver cancer prognosis while insulin treatment or sulphonylureas posed a serious threat. Mechanistically, the biological linkage between diabetes type II mellitus and liver cancer are still complex to understand with only the existence of a relationship between NAFLD and high level of energy intake and diabetes mellitus induces hepatic damage, increased liver weight thereby causes multiple pro-inflammatory cytokines that lead to the development of liver cancer. Therefore, this review gives an account of the pathophysiological importance of liver cancer position with T2DM, with the role of NAFLD as an important factor that bridges them. [ABSTRACT FROM AUTHOR]

Objectives: Hyphaene thebaica Mart. (locally known as Doum) is a well-known tropical plant and is traditionally used for the treatment of gastrointestinal tract (GIT) ulcers. The current study aimed to investigate the antioxidative and gastroprotective properties of H. thebaica fruit rind extract against experimentally ethanol-induced gastric ulceration in Sprague–Dawley rats. Materials and Methods: Two experiments were carried out: first, with 20 animals for dose selection and safety of the extract; then, a second with 30 animals for the gastric ulcer model. The two selected doses of H. thebaica extract (250 and 500 mg/kg) and antiulcer drug (omeprazole: 20 mg/kg) were administered through oral gavage for 2 weeks prior to ulcer induction. Acidity, mucus weight, ulcer area, and histopathology were used to assess the gastroprotective effects of H. thebaica extract. The antioxidative properties were assessed using the lipid peroxidation assay, non-protein thiol levels, superoxide dismutase activity, nitric oxide assay, and immunohistochemical staining of mitochondria-regulated apoptosis proteins such as Bax and Bcl-2. Results: In the current study, no in vivo toxicity of H. thebaica extract was observed. In the gastric model, preadministration of H. thebaica resulted in a significant reduction in ulcer area and mucus weight in a dose-dependent manner. Moreover, gross and histological findings confirmed the gastroprotective properties of H. thebaica extract. Quantitative assessment of microscopic lesions revealed a significant difference between the groups. These properties were observed to be mediated through the modulation of oxidative stress. H. thebaica modulated the Bcl-2 and Bax proteins and inhibited apoptosis. Conclusion: The gastroprotective properties of H. thebaica nominate it as a potential nutraceutical candidate. [ABSTRACT FROM AUTHOR]

The study investigated the effects of Zingiber officinale root and Vernonia amygdalina leaf on the brain redox status of Wistar rats. Twenty-four (24) rats weighing 160 ± 20 g were randomly assigned into four (4) groups, each with six (6) rats. Animals in Group 1 (control) were orally administered distilled water (1 mL), while the test groups were orally administered 5 mg/mL of either Z. officinale, V. amygdalina infusion, or a combination of both, respectively, for 7 days. The rats were sacrificed at the end of treatments and blood and tissue were harvested and prepared for biochemical assays. Results showed that administration of V. amygdalina and Z. officinale, as well as their coadministration, reduced the levels of malondialdehyde (MDA), nitric oxide (NO), acetylcholinesterase (AChE), and myeloperoxidase (MPO) in rat brain tissue compared with the control group. Conversely, coadministration of V. amygdalina and Z. officinale increased the levels of reduced glutathione (GSH) in rat brain tissue compared with the control group. However, the administration of the infusions singly, as well as the combination of both infusions, did not have any effect on the rat brain levels of glutathione peroxidase (GPx) and catalase (CAT) antioxidant enzymes compared to the control. Taken together, the findings indicate that the V. amygdalina and Z. officinale tea infusions have favorable antioxidant properties in the rat brain. The findings are confirmatory and contribute to deepening our understanding of the health-promoting effects of V. amygdalina and Z. officinale tea infusions. [ABSTRACT FROM AUTHOR]

Background. Diabetes is considered one of the most encyclopedic metabolic disorders owing to an alarming rise in the number of patients, which is increasing at an exponential rate. With the current therapeutics, which only aims to provide symptomatic and momentary relief, the scientists are shifting gears to explore alternative therapies which not only can target diabetes but can also help in limiting the progression of diabetic complications including diabetic neuropathy (DN). Methods. Tecoma stans leaf methanolic extract was prepared using the Soxhlet method. A streptozotocin (STZ; 45 mg/kg)-induced diabetic animal model was used and treatment with oral dosing of T. stans leaf extract at the different doses of 200 mg/kg, 300 mg/kg, and highest dose, i.e., 400 mg/kg, was initiated on day 3 after STZ administration. The pharmacological response for general and biochemical (angiogenic, inflammatory, and oxidative) parameters and behavioral parameters were compared using Gabapentin as a standard drug with the results from the test drug. Results. Parameters associated with the pathogenesis of diabetic neuropathy were evaluated. For general parameters, different doses of T. stans extract (TSE) on blood sugar showed significant effects as compared to the diabetic group. Also, the results from biochemical analysis and behavioral parameters showed significant positive effects in line with general parameters. The combination therapy of TSE at 400 mg/kg with a standard drug produced nonsignificant effects in comparison with the normal group. Conclusion. The leaves of T. stans possess antidiabetic effects along with promising effects in the management of DN by producing significant effects by exhibiting antioxidative, antiangiogenic, and anti-inflammatory properties, which are prognostic markers for DN, and thus, T. stans can be considered as an emerging therapeutic option for DN. [ABSTRACT FROM AUTHOR]

Perception of hub genes engaged in metastatic gastric cancer (mGC) promotes novel ways to diagnose and treat the illness. The goal of this investigation is to recognize the hub genes and reveal its molecular mechanism. In order to explore the potential facts for gastric cancer, the expression profiles of two different datasets were used (GSE161533 and GSE54129). The genes were confirmed to be part of the PPI network for gastric cancer pathogenesis and prognosis. In Cytoscape, the CytoHubba module was used to discover the hub genes. Responsible hub genes were identified. Data from Kaplan–Meier plotter confirmed the predictive value of these distinct genes in various stages of gastric malignancy. Upregulated and downregulated genes were identified to utilize for further analysis. Positive regulation by a host of viral process, positive regulation of granulocyte differentiation, negative regulation of histone H3–K9 methylation were found in DEGs analysis. In addition, five KEGG pathways were identified as an essential enhancer that include nucleotide excision repair; base excision repair; DNA replication; homologous recombination; and complement and coagulation cascades. POLE, BUB1B, POLD4, C3, BLM, CCT7, PRPF31, APEX1, PSMA7, and CDC45 were chosen as hub genes after combining the PPI results. Our study recommends that BUB1B, CCT7, APEX1, PSMA7, and CDC45 might be potential biomarkers for gastric cancer. These biomarkers are upregulated genes. Therefore, suppression of these genes will increase the survival rate in gastric cancer patients. [ABSTRACT FROM AUTHOR]

Rock mass classification systems are valuable tools for estimating design parameters of rock engineering projects. In some cases, due to the lack of enough geological data, it may not be possible to use a specific classification system. Many researchers have attempted to develop empirical correlations between classifications. However, these relationships are not applicable in all geological conditions and are highly site specific. Hence, it is necessary to introduce different geology-specific empirical relationships. In this paper, geological and engineering geological data from 107 sections of three mechanized tunneling projects, constructed in different geological zones of Iran, were collected, screened, and compiled in a database. To take into account the engineering geological conditions, the collected data were first categorized based on the conditions of rock masses in the tunnels. Two important parameters of lithology and rock mass structure were the basic criteria for categorizing the collected data. Then, the relationships between different classifications including RMR, Q, and GSI in categorized engineering geological conditions were investigated. In addition, for the first time, some empirical relationships between usual rock mass parameters and less-known parameters, which apply in the NTNU model (proposed for predicting TBM performance), were developed to facilitate the application of this model. Statistical analysis of the developed relationships shows that the geological characteristics are very important in development of these relationships. Parameters such as presence of clayey and foliated rocks, thickness of beds, and number of discontinuity sets are some of the factors that affect these relationships. [ABSTRACT FROM AUTHOR]

The CLEC-2 receptor protein belongs to the C-type lectin superfamily of transmembrane receptors that have one or more C-type lectin-like domains. CLEC-2 is a physiological binding receptor of podoplanin (PDPN), which is expressed on specific tumour cell types and involved in tumour cell-induced platelet aggregation and tumour metastasis. CLEC-2 and podoplanin-expressing tumour cells interact to increase angiogenesis, tumour development, and metastasis. CLEC-2 is a hemi-immunoreceptor tyrosine-based activation motif (hemi-ITAM) receptor located on platelets and a subset of dendritic cells that are expressed constitutively. This molecule is secreted by activated platelets around tumours and has been shown to inhibit platelet aggregation and tumour metastasis in colon carcinoma by binding to the surface of tumour cells. Pharmacokinetic studies were carried using a DrugLiTo, and molecular docking was performed using AutoDock Tools 1.5.6 (ADT). Twenty-nine bioactive compounds were included in the study, and four of them, namely, piperine, dihydrocurcumin, bisdemethoxycurcumin, and demothoxycurcumin, showed potential antagonist properties against the target. The resultant best bioactive was compared with commercially available standard drugs. Further, validation of respective compounds with an intensive molecular dynamics simulation was performed using Schrödinger software. To the best of our knowledge, this is the first report on major bioactive found on clove as natural antagonists for CLEC-2 computationally. To further validate the bioactive and delimit the screening process of potential drugs against CLEC-2, in vitro and in vivo studies are needed to prove their efficacy. [ABSTRACT FROM AUTHOR]

Extensive use of triclosan (2,4,4′‐trichloro‐2′‐hydroxydiphenyl ether) as an antimicrobial agent in household and personal care products has resulted in global exposure of the human population. Its presence in human tissues, including milk, and its oestrogen‐disrupting properties raise concerns for an involvement in breast cancer. Because metastatic tumour spread is the main cause of breast cancer mortality, we have investigated the effects of triclosan on cell migration and invasion using three human breast epithelial cell lines and using concentrations comparable with those in human tissues. Long‐term exposure to 10−7 M of triclosan resulted in increased migration and invasion as measured by xCELLigence technology for all three cell lines, for the immortalized but nontransformed MCF‐10F breast epithelial cells (after 28 weeks), the oestrogen‐responsive MCF‐7 breast cancer cells (after 17 weeks) and the oestrogen‐unresponsive MDA‐MB‐231 breast cancer cells (after 20 weeks). The effects were therefore not limited to cancerous cells or to oestrogen‐responsive cells. This was paralleled in the MCF‐10F and MCF‐7 (but not MDA‐MB‐231) cells by a reduction in levels of E‐cadherin mRNA as measured by reverse transcription–polymerase chain reaction (RT‐PCR) and of E‐cadherin protein as measured by western immunoblotting, suggesting a mechanism involving epithelial‐to‐mesenchymal transition. This adds triclosan to the increasing list of ingredients of personal care products that can not only enter human breast tissue and increase cell proliferation but also influence cell motility. If mixtures of components in household and personal care products contribute to increasing cell migration and invasion, then reduction in exposure could offer a strategy for reducing breast cancer spread. Long‐term (>15 weeks) exposure to 10−7 M of triclosan resulted in increased migration and invasion of three human breast epithelial cell lines as measured using xCELLigence technology. Effects were not limited to cancerous cells or to oestrogen‐responsive cells. In two cell lines, reduced levels of E‐cadherin (mRNA and protein) were observed, suggesting a mechanism involving epithelial‐to‐mesenchymal transition. Triclosan is therefore another ingredient of personal care products that is entering the human breast and increasing cell motility, which is a prerequisite for metastasis. [ABSTRACT FROM AUTHOR]

Background: Recently, there are clinical reports on the potential of Catha edulis (khat) to induce muscular toxicity. C. edulis (khat) is an evergreen shrub and a well-known controversial plant due to the content of natural stimulant, cathine and cathinone. Objective: The main objective of the study is to evaluate the possible effect of C. edulis leaves extract to induce rhabdomyolysis in vivo. Materials and Methods: Sprague Dawley rats were grouped and treated with khat extract at two different doses (250 and 500 mg/kg), while atorvastatin was used as positive control for 28 days. Body weight was measured throughout the study period. Overnight urine was collected from each rat at the 28th day for myoglobin (Myo) analysis. Terminal blood samples were collected from sacrificed animals for the measurement of serum biomarkers and clinical chemistry. The standard clinical pathology assays aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum creatinine (CR) were monitored. Skeletal muscle, cardiac muscle, and kidney were collected for histopathological examination. Results: Animals received 250 mg/kg khat extract had shown mild-to-no gait disorders, while at higher dose extract (500 mg/kg) had reduced the body weight of rats with marked increase of gait disorders compared to control. CR, AST, and ALT were elevated in high-dose administration and in rats received ethanol. The tested biomarkers such as heart-type fatty acid-binding protein (HFABP) 3, Troponin I Type 1 slow skeletal (TNNI1), and Myo were significantly increased in khat high dose and statin treatment, but not in low-dose extract and alcohol. The increase in HFABP and TNN1 results were well reflected in histopathological findings of skeletal myofiber degeneration and in the hemorrhages and pyknosis of nucleus observed in the cardiac muscle. Conclusion: These results provide evidence that khat chewing contributes to the development of muscle toxicity and probable rhabdomyolysis. The current subject thus warrants detailed studies which could emphasize on the cardiac complications and muscular toxicity mechanisms. [ABSTRACT FROM AUTHOR]

Background: Organophosphorus insecticides are well known to induce hepatotoxicity. One among this is chlorpyrifos (CPF), which is an insecticide inducing various toxicities including in liver. Objective: This investigation focused on CPF-induced oxidative damage in rat hepatocytes primary culture and the protective effect of Cactus cladode aqueous extract. Materials and Methods: Hepatocytes were treated with CPF (50, 75, and 150 μM) and cactus aqueous extract. On treatment for 48 h, mortality within these cells was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide test, reactive oxygen species (ROS) levels were measured by H2DCFDA test. Furthermore, heat shock protein 70 (HSP70) and CYP1A1/2 levels were determined using western blot analysis. Annexin V and 4',6-diamidino-2-phenylindole analysis was run to determine the level of cell death and cytoprotection exerted by CPF and extracts, respectively. Results: The results showed that CPF increases the levels of H2O2 and HSP70 and induces CYP1A1/2 and mortality within these cells. In the other side of this study, the co-treatment of these cells with CPF and Cactus cladode aqueous extract showed a recovery of these parameters. It also has been found that the Cactus cladode aqueous extract has the potential to do cytoprotective effect by preventing necrosis induced by CPF. Conclusion: Taken together, these findings suggest that the toxicity exerted by CPF in hepatocytes are involved with the generation of ROS and the regulation of well-controlled programmed cell death, which could be well protected by the Cactus cladode extract pretreatment. [ABSTRACT FROM AUTHOR]

Background: Tacrolimus is a known immunosuppressive drug used widely for organ transplantation, but its nephrotoxicity mechanism is still unclear. Objectives: The present study investigates the protective efficacy of Bacopa monnieri (BM), against tacrolimus-induced nephrotoxicity in rats. Materials and Methods: Group 1 (control group); administered orally with normal saline for 30 days; Group 2 (BM extract treated group); Group 3 (tacrolimus-treated group); and Group 4; (tacrolimus plus BM extract treated group). Tacrolimus-treated rats received 1 mg/kg body weight of tacrolimus intraperitoneally for 30 days, and BM-pretreated rats were administered with the dose of 200 mg/kg orally by gavage once a day for 30 days. Results: Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically. Pretreatment with BM has shown to possess a significant protective effect against tacrolimus-induced kidney functions regarding urea, creatinine, and albumin levels, respectively. The creatinine, mitochondrial lipid peroxidation (thiobarbituric acid reactive substances), and protein carbonyl levels were significantly increased dramatically, and however, the total proteins, albumin, glutathione, superoxide dismutase, and glutathione peroxidase were decreased when pretreated with tacrolimus. The nephroprotective efficacy of the BM extract was further evident by histopathological analysis and DNA fragmentation. Conclusion: The outcome of this study indicates that BM extracts exerted protection against tacrolimus-induced kidney toxicity. Abbreviations Used: ANOVA: Analysis of variance, BM: Bacopa monnieri, BUN: Blood urea nitrogen, DNPH: Dinitrophenylhydrazine, DPPH: 2,2-diphenyl-1-picrylhydrazyl, DSR: Deanship of Scientific Research, EOBPV: Egyptian Organization for Biological Products and Vaccines, GPx: Glutathione peroxidase, GSH: Glutathione, H and E: Hematoxylin and eosin, H2O2: Hydrogenperoxide, IAEC: Institutional Animals Ethics Committee, IC: Inhibitory concentration, Ip: Intraperitoneal, mLPO: Mitochondrial lipid peroxidation, Mn-SOD: Mn-superoxide dismutase, PC: Protein carbonyl, ROS: Reactive oxygen species. [ABSTRACT FROM AUTHOR]

Dermal absorption of components of personal care products (PCPs) may contribute to breast cancer development. Cyclic volatile methylsiloxanes (cVMS) are used widely in the formulation of PCPs, and their presence has been recently detected in human blood. The objectives of this study were to investigate any genotoxic effects after short- (1 week) or longer-term (30 weeks) exposure to hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4) or decamethylcyclopentasiloxane (D5) in MCF-10 A and MCF-10F immortalized non-transformed human breast epithelial cells. Genotoxic effects were assessed by an ability of cells to grow in suspension culture, from DNA damage measured by comet assays, and from a reduction in levels of DNA repair proteins measured by RT-PCR and western immunoblotting. Dose-dependent anchorage-independent growth in methocel culture was observed after exposure to D3 (10−13 M-10−5 M) and D4/D5 (10−9 M-10−5 M). DNA damage was measured by the comet assay after 1-h exposure to D3 (10−6 M-10−5 M) and D4 (10−5 M). BRCA1 mRNA and BRCA1 protein levels were reduced after 30-week exposure to 10−5 M D4 and D5 in both cell lines. Reduced levels of mRNAs for other DNA repair proteins (BRCA2, ATM, ATR, CHK1 and CHK2) were also observed after exposure to 10−5 M D5 in both cell lines, and some reductions after exposure to D3 and D4. If cVMS can not only enable anchorage-independent growth of non-transformed breast epithelial cells and damage DNA, but also compromise DNA repair systems, then there is the potential for them to impact on breast carcinogenesis. Further risk assessment now requires information concerning the extent to which cVMS may be present in human breast tissues. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The Curcuma longa plant is endowed with multiple traditional and therapeutic utilities and is here explored for its phytochemical constituents and cytotoxic potential. Turmeric rhizomes were extracted from three different solvents and screened for the presence of different phytochemical constituents, observation of which indicated that the polar solvents favoured extraction of greater versatile phytochemical constituents. These extracts were investigated for their cytotoxic potential by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on three different of cell lines including SCC-29B (oral cancer cell line), DU-145 (prostate cancer cell line) and the Vero cell line (healthy cell line/non-cancerous cell line). This assay was performed by taking three extracts from isolated curcuminoids and a pure bioactive compound bisdemethoxycurcumin (BD). Bisdemethoxycurcumin was isolated from curcuminoids and purified by column and thin-layer chromatography, and its structural characterisation was performed with different spectroscopic techniques such as FTIR, NMR (1H Proton and 13C Carbon-NMR) and LC-MS. Amongst the extracts, the ethanolic extracts exhibited stronger cytotoxic potential against the oral cancer cell line (SCC-29B) with an IC50value of 11.27 μg/mL, and that this was too low of a cytotoxicity against the Vero cell line. Although, curcuminoids have also shown a comparable cytotoxic potential against SCC-29B (IC50 value 16.79 μg/mL), it was not as potent against the ethanolic extract, and it was even found to be cytotoxic against healthy cell lines at a very low dose. While considering the isolated compound, bisdemethoxycurcumin, it also possessed a cytotoxic potential against the prostate cancer cell line (DU-145) (IC50 value of 93.28 μg/mL), but was quite safe for the healthy cell line in comparison to doxorubicin. [ABSTRACT FROM AUTHOR]