Role of nutraceutical against exposure to pesticide residues: power of bioactive compounds.

Pesticides play a crucial role in modern agriculture, aiding in the protection of crops from pests and diseases. However, their indiscriminate use has raised concerns about their potential adverse effects on human health and the environment. Pesticide residues in food and water supplies are a serious health hazards to the general public since long-term exposure can cause cancer, endocrine disruption, and neurotoxicity, among other health problems. In response to these concerns, researchers and health professionals have been exploring alternative approaches to mitigate the toxic effects of pesticide residues. Bioactive substances called nutraceuticals that come from whole foods including fruits, vegetables, herbs, and spices have drawn interest because of their ability to mitigate the negative effects of pesticide residues. These substances, which include minerals, vitamins, antioxidants, and polyphenols, have a variety of biological actions that may assist in the body's detoxification and healing of harm from pesticide exposure. In this context, this review aims to explore the potential of nutraceutical interventions as a promising strategy to mitigate the toxic effects of pesticide residues.

Comparative phenotypic and genotypic analysis of community-acquired and hospital-acquired intra-abdominal infections among liver transplanted patients.

AIM: During liver transplantation, both hospital-acquired (HA) and community-acquired (CA) intra-abdominal infections (IAIs) are involved causing life-threatening diseases. Therefore, comparative studies of aerobic and facultative anaerobic HA-IAIs and CA-IAIs after liver transplantation surgery are necessary. METHODS AND RESULTS: The species of detected isolates (310) from intra-abdominal fluid were identified and classified into hospital-acquired intra-abdominal infections (HA-IAIs) and community-acquired intra-abdominal infections (CA-IAIs). Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii were the most commonly detected species. The resistant phenotypes were commonly detected among the HA-IAIs; however, the virulent phenotypes were the predominant strains of CA-IAIs. Regrettably, the resistance profiles were shocking, indicating the inefficacy of monotherapy in treating these isolates. Therefore, we confirmed the use of empirical combination therapies of amikacin and meropenem for treating all IAIs (FICI ≤ 0.5). Unfortunately, the high diversity and low clonality of all identified HA and CA-IAIs were announced with D-value in the range of 0.992-1. CONCLUSION: This diversity proves that there are infinite numbers of infection sources inside and outside healthcare centers.

Bone morphogenetic protein 1: a prognostic indicator and potential biomarker in three cancer types.

BACKGROUND: Bone morphogenetic protein 1 (BMP1) is a metalloprotease that plays a role in activating both transforming growth factor-ß (TGF-ß) and BMP signaling pathways. TGF-ß has been identified as a factor initiating and facilitating cancer development. Consequently, we propose the hypothesis that dysregulation of BMP1 could potentially contribute to the onset and advancement of human cancers. METHODS: In this research, we aimed to analyze BMP1 expression level and the associated clinical outcomes across various cancers using online cancer OMICS databases, advanced Bioinformatics tools, and molecular analyses. RESULTS: The outcomes of our web server-based expression analysis indicated an up-regulation of BMP1 in a majority of the human cancers examined. External validation using clinical samples also showed higher expression of BMP1. Moreover, heightened BMP1 expression exhibited a noteworthy correlation with reduced overall survival (OS) duration in Bladder Cancer (BLCA), Kidney Renal Clear Cell Carcinoma (KIRC), and Lung Adenocarcinoma (LUAD) patients. This suggests a substantial involvement of the BMP1 gene in the development and progression of these three types of cancers. The major signaling pathways related with BMP1 enriched genes were "ECM-receptor interaction, Amoebiasis, Focal adhesion, Protein digestion and absorption, progesterone-mediated, PI3K-Akt signaling pathway, and platelet activation". Moreover, we also explored some interesting correlations among BMP1 expression and its DNA promoter methylation level, CD8+ T immune cells level, and genetic variations. CONCLUSION: In conclusion, our study has provided some solid basis for BMP1 to be used as a reliable common biomarker for BLCA, KIRC, and LUAD patients.

Isolation, preparation and investigation of leaf extracts of Aloe barbadensis for its remedial effects on tumor necrosis factor alpha (TNF-α) and interleukin (IL-6) by in vivo and in silico approaches in experimental rats.

Aloe barbadensis is a stemless plant with a length of 60-100 cm with juicy leaves which is used for its remedial and healing properties in different suburbs of various countries. The present study was conducted to investigate the effect of A. barbadensis leaf extract (aqueous and ethanolic) in yeast induced pyrexia and acetic acid induced writhing in rat model to evaluate the antipyretic biomarkers and its phytochemical screening with computational analysis. For analgesic activity model 60 Albino rats (160-200 kg) were divided into four groups. Of the 4 groups, control consisted of 6 rats (Group I) treated with normal saline, standard comprised of 6 rats treated with drug diclofenac (Group I). Experimental groups consisted of 48 rats, treated with A. barbadensis ethanolic and aqueous leaf extracts at doses of 50 mg/kg, 100 mg/kg, 200 mg/kg, and 400 mg/kg (Group III. IV). For antipyretic activity group division was same as in analgesic activity. All groups were treated the same as in the analgesic activity except for the second group which was treated with paracetamol. In both antipyretic and analgesic activity at the dose of 400 mg/kg, group III showed significant inhibition. TNF-α and IL-6 showed significant antipyretic activity at a dose of 400 mg/kg. For molecular docking aloe emodin and cholestanol were used as ligand molecules to target proteins Tnf-α and IL-6. Acute oral toxicity study was performed. There was no mortality even at the dose of 2000 mg/kg. Quantitative and qualitative phytochemical screening was performed for the detection of various phytochemicals. Hence, A. barbadensis leaf extracts can be used in the form of medicine for the treatment of pain and fever.

Anesthesia and surgery induce changes in endogenous brain protective protein (RNF146) and delirium-like behavior in aged rats.

BACKGROUND: Postoperative delirium (POD) is a common complication after anesthesia and surgery, especially in the elderly. RNF146 has neuroprotective effects in cerebral ischemia, hypoxia, and chronic neurological diseases. However, whether RNF146 expression is related to the occurrence and development of POD remains unclear. Therefore, in this study, we aimed to determine whether RNF146 is involved in the occurrence of POD. METHODS: (Sprague-Dawley) male rats (18 months old) were splenectomized under sevoflurane anesthesia. The cognitive function of rats at 1, 3, and 7 d after anesthesia and surgery was evaluated. Changes in the expression of neuroinflammatory cytokines, IL-6 and IL-10, and RNF146 were measured in the hippocampus in both control group (con) and anesthesia (AS) group. We examined cognitive outcomes and expression of inflammatory factors and RNF146 in con and AS mice using cluster analysis. RESULTS: The cognitive ability and mobility of rats after anesthesia and surgery at day 1, 3, and 7 decreased, especially at day 3. Similarly, the expression of neuroinflammatory factors and RNF146 increased after anesthesia and surgery at day 1, 3, and 7, and the increase was highest at day 3. The clustering and correlation analysis of RNF146 expression in the hippocampi of elderly rats revealed a correlation between POD and neuroinflammation resulting from anesthesia and surgery. CONCLUSION: Anesthesia and surgery can lead to POD and neuroinflammation. The expression of RNF146 correlates with delirium and neuroinflammation caused by anesthesia and surgery.

In vitro analysis of PI3K pathway activation genes for exploring novel biomarkers and therapeutic targets in clear cell renal carcinoma.

OBJECTIVES: The regulation of various cellular functions such as growth, proliferation, metabolism, and angiogenesis, is dependent on the PI3K pathway. Recent evidence has indicated that kidney renal clear cell carcinoma (KIRC) can be triggered by the deregulation of this pathway. The objective of this research was to investigate 25 genes associated with activation of the PI3K pathway in KIRC and control samples to identify four hub genes that might serve as novel molecular biomarkers and therapeutic targets for treating KIRC. METHODS: Multi-omics in silico and in vitro analysis was employed to find hub genes related to the PI3K pathway that may be biomarkers and therapeutic targets for KIRC. RESULTS: Using STRING software, a protein-protein interaction (PPI) network of 25 PI3K pathway-related genes was developed. Based on the degree scoring method, the top four hub genes were identified using Cytoscape's Cytohubba plug-in. TCGA datasets, KIRC (786-O and A-498), and normal (HK2) cells were used to validate the expression of hub genes. Additionally, further bioinformatic analyses were performed to investigate the mechanisms by which hub genes are involved in the development of KIRC. Out of a total of 25 PI3K pathway-related genes, we developed and validated a diagnostic and prognostic model based on the up-regulation of TP53 (tumor protein 53) and CCND1 (Cyclin D1) and the down-regulation of PTEN (Phosphatase and TENsin homolog deleted on chromosome 10), and GSK3B (Glycogen synthase kinase-3 beta) hub genes. The hub genes included in our model may be a novel therapeutic target for KIRC treatment. Additionally, associations between hub genes and infiltration of immune cells can enhance comprehension of immunotherapy for KIRC. CONCLUSION: We have created a new diagnostic and prognostic model for KIRC patients that uses PI3K pathway-related hub genes (TP53, PTEN, CCND1, and GSK3B). Nevertheless, further experimental studies are required to ascertain the efficacy of our model.

Valorization of different low-grade date (Phoenix dactylifera L.) fruit varieties: A study on the bioactive properties of polyphenolic extracts and their stability upon in vitro simulated gastrointestinal digestion.

Nowadays, the development of suitable strategies for the management and valorization of agri-food products is one of the most important challenges worldwide. In this context, the current research study aimed to explore a valorization strategy for different varieties (Khalas, Jabri, Lulu, Booman, and Sayer) of low-grade date fruit by extracting polyphenolic compounds and investigating their health-promoting bioactive properties. The generated extracts were comparatively analyzed for their phenolic contents, antioxidant, anti-inflammatory, anti-hemolytic, and enzyme inhibitory activities upon in vitro simulated gastrointestinal digestion (SGID). The total phenolic contents (TPC) ranged from 217.3 to 1846.9 mg GAE/100 g fresh weight. After complete SGID, the TPC remarkably increased from 570.8 mg GAE/100 g fresh weight (undigested), reaching the highest value of 1606.3 mg GAE/100 g fresh weight with the Khalas cultivar. Overall, gastric and complete-SGID-treated extracts exhibited higher antioxidant activities, compared to the undigested extracts for the five selected date varieties. Similarly, the gastric and complete SGID promoted the release of bioactive components endowed with significantly higher inhibition levels towards digestive enzymes related to diabetes. Moreover, extracts from all varieties revealed an increase in the inhibition of lipidemic-related enzymatic markers and anti-inflammatory activities when subjected to the gastric digestion phase, which decreased after complete SGID. Principal component analysis (PCA) suggested that higher bioactive properties were influenced by the TPC present in the samples. Overall, low-quality dates could be considered as a potential source of bioactive polyphenols with interesting nutraceutical properties, released upon their transit through the gastrointestinal tract.

Effect of histone deacetylase inhibitor (vorinostat) on new-onset diabetes induced by tacrolimus.

Objective: The immunosuppressant tacrolimus is a major cause of new-onset diabetes after transplantation. The aim of this study was to evaluate whether a low dose of the histone-deacetylase inhibitor (vorinostat) might ameliorate tacrolimus-induced new-onset diabetes. Methods: Thirty 8-week-old male Wistar rats were randomly divided into five groups: a control group, tacrolimus group (1.5 mg/kg intraperitoneally for 28 days), vorinostat group (15 mg/kg orally for 28 days), a group receiving tacrolimus with vorinostat for 28 days; and a group receiving coadministration of tacrolimus for 28 days and vorinostat for 14 days. Diabetes development was assessed on the basis of serum glucose, insulin, HOMA-IR and C-peptide. To investigate the mechanism of vorinostat, we assessed inflammatory markers (tumor necrosis factor-α and interleukin-1ß), an antioxidant marker (glutathione), an oxidant marker (nicotinamide adenine dinucleotide phosphate hydrogen oxidase) and an apoptosis marker (caspase-3). Kidney functions (creatinine and blood urea nitrogen) were also assessed. Results: The administration of tacrolimus for 28 days resulted in significantly increased serum glucose and decreased C-peptide and insulin levels than those in the control group. However, coadministration of vorinostat significantly decreased hyperglycemia and increased C-peptide and insulin levels. Moreover, combined treatment with tacrolimus and vorinostat, compared with tacrolimus treatment alone, resulted in significantly reduced inflammatory and oxidant markers, and increased glutathione. Additionally, vorinostat improved the kidney parameters. Conclusion: Vorinostat at a low dose (15 mg/kg) induces anti-inflammatory and antioxidative effects that protect the pancreas and kidney against the development of new-onset diabetes due to tacrolimus in rats. This experimental study provides insights supporting further clinical trials to improve the post-kidney transplantation protocol through addition of vorinostat to the immunosuppressive regimen.

Region-Based Segmentation and Classification for Ovarian Cancer Detection Using Convolution Neural Network.

Ovarian cancer is a serious sickness for elderly women. According to data, it is the seventh leading cause of death in women as well as the fifth most frequent disease worldwide. Many researchers classified ovarian cancer using Artificial Neural Networks (ANNs). Doctors consider classification accuracy to be an important aspect of making decisions. Doctors consider improved classification accuracy for providing proper treatment. Early and precise diagnosis lowers mortality rates and saves lives. On basis of ROI (region of interest) segmentation, this research presents a novel annotated ovarian image classification utilizing FaRe-ConvNN (rapid region-based Convolutional neural network). The input photos were divided into three categories: epithelial, germ, and stroma cells. This image is segmented as well as preprocessed. After that, FaRe-ConvNN is used to perform the annotation procedure. For region-based classification, the method compares manually annotated features as well as trained feature in FaRe-ConvNN. This will aid in the analysis of higher accuracy in disease identification, as human annotation has lesser accuracy in previous studies; therefore, this effort will empirically prove that ML classification will provide higher accuracy. Classification is done using a combination of SVC and Gaussian NB classifiers after the region-based training in FaRe-ConvNN. The ensemble technique was employed in feature classification due to better data indexing. To diagnose ovarian cancer, the simulation provides an accurate portion of the input image. FaRe-ConvNN has a precision value of more than 95%, SVC has a precision value of 95.96%, and Gaussian NB has a precision value of 97.7%, with FR-CNN enhancing precision in Gaussian NB. For recall/sensitivity, SVC is 94.31 percent and Gaussian NB is 97.7 percent, while for specificity, SVC is 97.39 percent and Gaussian NB is 98.69 percent using FaRe-ConvNN.

Role of polycystic ovarian syndrome in developing psychological burden in Saudi Arabian females: A case control study.

It is well known that polycystic ovarian syndrome (PCOS) may elevate psychological problems in patients, but there is a scarcity of the studies among Saudi Arabian population. This research was designed to investigate the influence of PCOS on the development of psychological load in terms of depression, anxiety, and stress in comparison to normal women who have no PCOS. Further, a correlation of psychological distress in PCOS females was done with their educational level. This is case-control research carried out in one of Riyadh's multispecialty hospitals. In the PCOS patients and control groups (each with 84 samples), samples were collected using convenience sampling and a simple random approach, respectively. The psychological burden was determined using DASS-21. The data obtained were analyzed using SPSS-IBM 25. Most participants (52.9%) were between the ages of 26 and 35 and had a university education (68.4%). A significantly higher percentage of PCOS patients (P = 0.001) had irregular menses, hirsutism, infertility, and acne in comparison to the mothers without PCOS. There was a significantly higher possibility of depression (P = 0.003), anxiety (P = 0.016), and stress (P = 0.001) among PCOS patients than in control subjects. Among the psychological domain tested in the study, the risk of developing stress (odds ratio, OR = 8.32) was high when compared to depression (OR = 3.12) and anxiety (OR = 2.127) in PCOS patients. Furthermore, when compared to PCOS females with less education, a significantly lower number of university-educated PCOS females developed depression. The study demonstrates a high prevalence of psychological burden among the PCOS population. Higher education has been shown to help in alleviating depression in PCOS females. Meeting PCOS women's psychological needs will improve their overall health status.

The Influence of Prenatal Exposure to Quetiapine Fumarate on the Development of Dopaminergic Neurons in the Ventral Midbrain of Mouse Embryos.

The effects of second-generation antipsychotics on prenatal neurodevelopment, apoptotic neurodegeneration, and postnatal developmental delays have been poorly investigated. Even at standard doses, the use of quetiapine fumarate (QEPF) in pregnant women might be detrimental to fetal development. We used primary mouse embryonic neurons to evaluate the disruption of morphogenesis and differentiation of ventral midbrain (VM) neurons after exposure to QEPF. The dopaminergic VM neurons were deliberately targeted due to their roles in cognition, motor activity, and behavior. The results revealed that exposure to QEPF during early brain development decreased the effects of the dopaminergic lineage-related genes Tyrosine hydroxylase(Th), Dopamine receptor D1 (Drd1), Dopamine transporter (Dat), LIM homeobox transcription factor 1 alfa (Lmx1a), and Cell adhesion molecule L1 (Chl1), and the senescent dopaminergic gene Pituitary homeobox 3 (Pitx3). In contrast, Brain derived neurotrophic factor (Bdnf) and Nuclear receptor-related 1 (Nurr1) expressions were significantly upregulated. Interestingly, QEPF had variable effects on the development of non-dopaminergic neurons in VM. An optimal dose of QEPF (10 µM) was found to insignificantly affect the viability of neurons isolated from the VM. It also instigated a non-significant reduction in adenosine triphosphate formation in these neuronal populations. Exposure to QEPF during the early stages of brain development could also hinder the formation of VM and their structural phenotypes. These findings could aid therapeutic decision-making when prescribing 2nd generation antipsychotics in pregnant populations.

Antidepressant Effect of Crocin in Mice with Chronic Mild Stress.

This study aimed to investigate the antidepressant property of crocin (Crocetin digentiobiose ester) using a chronic mild stress (CMS)-induced depression model in experimental mice. The tail suspension test (TST) and the sucrose preference test were used to evaluate the antidepressant effect on albino mice of either sex after three weeks of CMS. The period of immobility in the TST and percentage preference for sucrose solution were recorded. By monitoring brain malondialdehyde (MDA) level, catalase (CAT) activity, and reduced glutathione (GSH) level, the antioxidant potential was assessed. Three dosages of crocin (4.84, 9.69, and 19.38 mg/kg) were evaluated. When compared to controls, animals that received crocin administration during three periods of CMS had considerably shorter immobility times during the TST. Crocin treatment also raised the percentage preference for sucrose solution in a dose-dependent manner, bringing it to parity with the conventional antidepressant, imipramine. Animals that received a high dose of crocin had a much greater spontaneous locomotor activity. Furthermore, a high dose of crocin remarkably lowered plasma corticosterone and nitrite levels brought on by CMS. Additionally, high doses of crocin given during CMS greatly enhanced reduced glutathione levels while considerably reducing the brain's MDA and catalase activities. In conclusion, high doses of crocin may have an antidepressant effect in an animal model through several mechanisms. However, further studies should be carried out to explore the role of neurotransmitters for their antidepressant property.

Boosting the anti MERS-CoV activity and oral bioavailability of resveratrol via PEG-stabilized emulsomal nano-carrier: Factorial design, in-vitro and in-vivo assessments.

Resveratrol (RSV) is a phytoceutical polyphenolic compound exhibiting a well evidenced wide range of therapeutic activities. Unfortunately, its diminished aqueous solubility and extensive metabolism in gastro intestinal tract (GIT) and liver prohibit its biological activity and systemic availability. Herein the conducted study PEG stabilized emulsomes (PEMLs) were customized to enclose RSV aiming to boost its biological availability and antiviral activity. PEGylating the vesicles not only grant the promoted steric stability of the system but also being beneficial in exaggerating the intestinal permeability and extending the period of circulation of the drug, hence its targeted clinical use. The Investigation of the influence of predetermined variables on the physical characterization of formulae (entrapment efficiency EE%, particle size PS and zeta potential ZP) was implemented utilizing Design Expert® software. (F4) with desirability value (0.772), picked to be the optimal formula, which is fabricated utilizing 35 mg compritol as the lipidic core and 60 mg 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-Mpeg-2000). The dominance of the F4 relative to RSV dispersion was affirmed by the data acquired from ex-vivo and pharmacokinetic studies. In addition, F4 exhibited significant lower EC50 value (0.0127 µg/mL) relative to that of RSV dispersion(0.338 µg/mL) by around 26 times denoting the capability of the formulation to boost the antiviral activity. To a great extent, F4 was able to significantly suppress the inflammatory response and oxidative stress resulted from MERS-CoV infection on comparison with RSV dispersion. Finally, the potentiality of PEMLs as nano-panel with boosted both antiviral and oral bioavailability for RSV could be deduced based on the outcomes mentioned herein.

Green Synthesis of Silver Nanoparticles Using the Plant Extract of Acer oblongifolium and Study of Its Antibacterial and Antiproliferative Activity via Mathematical Approaches.

In this study, the antibacterial and antifungal properties of silver nanoparticles synthesized with the aqueous plant extract of Acer oblongifolium leaves were defined using a simplistic, environmentally friendly, reliable, and cost-effective method. The aqueous plant extract of Acer oblongifolium, which served as a capping and reducing agent, was used to biosynthesize silver nanoparticles. UV visible spectroscopy, X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and scanning electron microscopy were used to analyze the biosynthesized Acer oblongifolium silver nanoparticles (AgNPs). Gram-positive bacteria (Bacillus paramycoides and Bacillus cereus) and Gram-negative bacteria (E. coli) were used to test the AgNPs' antibacterial activity. The presence of different functional groups was determined by FTIR. The AgNPs were rod-like in shape. The nanoparticles were more toxic against Escherichiacoli than both Bacillus cereus and Bacillus paramycoides. The AgNPs had IC50 values of 6.22 and 9.43 and mg/mL on HeLa and MCF-7, respectively, proving their comparatively strong potency against MCF-7. This confirmed that silver nanoparticles had strong antibacterial activity and antiproliferative ability against MCF-7 and HeLa cell lines. The mathematical modeling revealed that the pure nanoparticle had a high heat-absorbing capacity compared to the mixed nanoparticle. This research demonstrated that the biosynthesized Acer oblongifolium AgNPs could be used as an antioxidant, antibacterial, and anticancer agent in the future.

Folate-Modified Chitosan 5-Flourouraci Nanoparticles-Embedded Calcium Alginate Beads for Colon Targeted Delivery.

Gel beads are formed when alginate acid reacts with divalent cations, particularly Ca2+. As a result of this feature, it is one of the best materials for making gel beads. Furthermore, it swells only slightly at acidic pH, resulting in stable alginate acid beads, but swells and dissolves rapidly at higher pH values, leading to pH-responsive release. Our current study aimed to embed folate-modified chitosan 5FU nanoparticles (FA-CS-5FU-NPs) into calcium alginate beads for colon-targeted delivery. Calcium alginate beads were developed successfully. Based on the method of drying, two types of beads were obtained: freeze-dried folate-modified chitosan 5FU nanoparticles-embedded beads (FA-CS-5FU-NP-Bf) and oven-dried folate-modified chitosan 5FU nanoparticles-embedded beads (FA-CS-5FU-NP-Bo). The size of (FA-CS-5FU-NP-Bf) was significantly larger than (FA-CS-5FU-NP-Bo). Swelling index (SI), erosion index (EI), and water-uptake index (WUI) of (FA-CS-5FU-NP-Bf) beads were significantly higher than FA-CS-5FU-NP-Bo beads at simulated intestinal pH. An insignificant difference was observed in the release rate of 5FU between (FA-CS-5FU-NP-Bf) and FA-CS-5FU-NP-Bo. The release rate of FA-CS-5FU-NPs was significantly higher than FA-CS-5FU-NP-Bf and FA-CS-5FU-NP-Bo. Pharmacokinetic parameters of 5FU solution, FA-CS-5FU-NPs, and FA-CS-5FU-NP-Bo were analyzed. Solution of pure 5FU showed significantly higher Cmax and lower AUC, T1/2, and Vd than both FA-CS-5FU-NPs and FA-CS-5FU-NPs-Bo, suggesting that FA-CS-5FU-NPs and FA-CS-5FU-NPs-Bo have sustained-release behavior. Biodistribution studies also show that maximum drug amounts were found in the colon from nanoparticles-embedded beads. FA-CS-5FU-NPs-Bo avoid releasing drugs in the stomach and small intestine and make them available in the colon region in higher concentrations to target the colon region specifically.

Tissue Expression Analysis, Cloning, and Characterization of the 5'-Regulatory Region of the Bovine LATS1 Gene.

As a member of the large tumor suppressor (LATS) gene family, LATS1 plays an important role in regulating muscle growth and development. In this study, we determined the distinct exhibit patterns of tissue expression of bovine LATS1. Further, we determined the functional proximal minimal promoter of bovine LATS1 and identified the key transcription factors in the core promoter region to elucidate its molecular regulation mechanism. The results showed that bovine LATS1 was highly expressed in the longissimus thoracis and upregulation in infancy muscle. An electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay in combination with site-directed mutation and small interfering RNA (siRNA) interference demonstrated that myogenic differentiation 1 (Myod1) and myocyte enhancer factor 2A (MEF2A) binding in the core promoter region (-298/-123 bp) play important roles in the transcriptional regulation of the bovine LATS1 promoter. Taken together, these interactions provide insight into the regulatory mechanisms of LATS1 transcription in mediating skeletal muscle growth in cattle.

Integrative global co-expression analysis identifies key microRNA-target gene networks as key blood biomarkers for obesity.

BACKGROUND: Obesity is associated with the quantitative changes in miRNAs and their target genes. However, the molecular basis of their dysregulation and expression status correlations is incompletely understood. Therefore, this study aims to examine the shared differentially expressed miRNAs and their target genes between blood and adipose tissues of obese individuals to identify potential blood-based biomarkers. METHODS: In this study, 3 gene expression datasets (two mRNA and one miRNA), generated from blood and adipose tissues of 68 obese and 39 lean individuals, were analyzed by a series of robust computational concepts, like protein interactome mapping, functional enrichment of biological pathways and construction of miRNA-mRNA and transcription factor gene networks. RESULTS: The comparison of blood versus tissue datasets has revealed the shared differential expression of 210 genes (59.5% upregulated) involved in lipid metabolism and inflammatory reactions. The blood miRNA (GSE25470) analysis has identified 79 differentially expressed miRNAs (71% downregulated). The miRNA-target gene scan identified regulation of 30 shared genes by 22miRNAs. The gene network analysis has identified the inverse expression correlation between 8 target genes (TP53, DYSF, GAB2, GFRA2, NACC2, FAM53C, JNK and GAB2) and 3 key miRNAs (hsa-mir-940, hsa-mir-765, hsa-mir-612), which are further regulated by 24 key transcription factors. CONCLUSIONS: This study identifies potential obesity related blood biomarkers from large-scale gene expression data by computational miRNA-target gene interactome and transcription factor network construction methods.

Potential benefits of gallic acid as skeletal muscle relaxant in animal experimental models.

BACKGROUND AND OBJECTIVE: Many natural bioactive chemicals have been shown to have functional activity, suggesting that they could be useful in the treatment and management of a wide range of chronic conditions. Flavonoids, which include gallic acid (GA), are the most abundant polyphenols found in nature. Skeletal muscle relaxants are drugs that reduce undesired spasms while maintaining awareness and reflexes unaffected. The purpose of this investigation was to determine if GA has any skeletal muscle relaxant properties in experimental animal models. MATERIALS AND METHODS: The muscle relaxant activity of three dosages of GA (5, 10, and 20 mg/kg) was compared to that of normal diazepam (5 mg/kg) utilizing climbing, chimney, and modified Kondziela's inverted tests. An analysis of variance (ANOVA) and a post-ANOVA Tukey multiple comparisons test were used to assess the data. RESULTS: Animals given 10 and 20 mg/kg of GA had a great deal of trouble climbing up the chain, presumably because their muscles were relaxed. Similarly, rats given a high dose of GA (20 mg/kg) had a significantly (P < 0.05) longer response time in the chimney test, indicating a lack of attention and slowed muscle tone, resulting in problems with motor coordination. In inverted testing, animals given a high dose of GA had a significantly (P < 0.01) reduced holding capacity on the mesh for a longer period of time. A decrease in holding time is caused by a decrease in muscular contraction. The low dose of GA, on the other hand, failed to show muscle relaxant effect in any of the three models. CONCLUSIONS: As a conclusion, our data show that GA has a dose-dependent skeletal muscle relaxant effect when administered orally to mice.

The Potential Benefits of Using Garlic Oil and Its Active Constituent, Dially Disulphide, in Combination With Carvedilol in Ameliorating Isoprenaline-Induced Cardiac Damage in Rats.

Garlic oil and its primary component, diallyl disulphide (DADS), were tested in rats with isoprenaline (ISO) induced myocardial infarction for cardioprotective benefits when combined with carvedilol. Garlic oil (GO) was administered to rats (Sprague-dawley strain) at two doses of 50 and 100 mg/kg body weight, whereas DADS was given in two doses of 4.47 and 8.94 mg/kg, respectively. The animals were given oral doses of garlic oil and DADS on alternate days for 3 weeks, either alone or in combination with carvedilol (2 mg/kg). Cardiac injury was done by administering two doses of isoprenaline (150 mg/kg, sc) to all treated groups except the first, which served as a control. Biomarkers of cardiac injury and histological investigations were studied for their potential in reducing ISO-induced myocardial damage. Animals pretreated with GO, DADS, and carvedilol had significantly (p < 0.01) lowered heart weight and heart to body weight ratio. In rats treated with carvedilol plus high dosages of garlic oil (100 mg/kg, p.o) and DADS (8.94 mg/kg, p.o) compared to the ISO control and carvedilol group, the activities of SOD and Catalase were enhanced in cardiac tissue homogenate. When compared to ISO control and carvedilol group, the activities of LDH and CK-MB were elevated in heart tissue homogenate with a simultaneous reduction in their serum levels in animals treated with a combination of carvedilol with high doses of garlic oil (100 mg/kg, p.o) and DADS (8.94 mg/kg, p.o). Overall, combining garlic oil or DADS with carvedilol improved the cardioprotective effect of carvedilol and protected rats from ISO-induced myocardial infarction. However, more research is needed to establish the mechanism of garlic oil and DADS interaction with carvedilol.

Cardioprotective Potential of Garlic Oil and Its Active Constituent, Diallyl Disulphide, in Presence of Carvedilol during Chronic Isoprenaline Injection-Mediated Myocardial Necrosis in Rats.

In isoprenaline (ISO)-induced myocardial infarcted rats, garlic oil (GO) and its main ingredient, diallyl disulfide (DADS), were examined for cardioprotective effects when used with carvedilol (CAR). GO, DADS and CAR were given to rats in their respective groups, either alone or together, with the addition of isoprenaline (3 mg/kg/day, subcutaneously) during the last 10 days of treatment. At the end of 14 days of treatment, blood samples were collected, the hearts were excised under anesthesia and weighed. Heart tissue homogenate was used to measure superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid reactive substances (TBARS). Furthermore, the serum activities of cardiac markers, including lactate dehydrogenase, creatine kinase, and cardiac troponin, were checked. Moreover, inflammatory markers including tumor necrosis factor alpha, interleukin one beta, interleukin six, and kappa bp65 subunit were assessed. Rats that received GO, DADS, and CAR exhibited a significant increase in the cardiac antioxidant enzyme activities with a simultaneous decrease in serum cardiac markers enzymes and inflammatory markers. The TBARS were significantly reduced in rats that received treatment. The addition of carvedilol to GO or DADS significantly elevated antioxidant activities and decreased the release of cardiac enzymes into blood circulation. Both DADS and GOl were almost similar in efficacy, indicating the potential role of DADS in garlic oil-mediated cardioprotection. Combining GO or DADS with CAR increased CAR's cardioprotective impact and protected rats from developing ISO-induced myocardial infarction.