Exploration of transcriptional regulation network between buffalo oocytes and granulosa cells and its impact on different diameter follicles.

BACKGROUND: Buffalo is a globally important livestock species, but its reproductive performance is relatively low than cattles. At present, dominant follicle development specific process and mechanistic role of follicular growth related genes in water buffaloes are not well understood. Therefore, we comprehensively performed transcriptomics of granulosa cells and oocytes from different-sized follicles in water buffalo to identify key candidate genes that influence follicle development and diameter, and further explored the potential regulatory mechanisms of granulosa cells and oocytes in the process of water buffalo follicle development. RESULTS: In this study, we found918 granulosa cell transcripts and 1401 oocyte transcripts were correlated in follicles of different diameters, and the expression differences were significant. Subsequent enrichment analysis of the co-expressed differentially expressed transcripts identified several genes targeted by long non-coding RNAs (lncRNAs) and associated with follicular development. Notably, the upregulation of BUB1 regulated by MSTRG.41325.4 and interactive action of SMAD2 and SMAD7 might have key regulatory role in follicular development. Additionally, we also detected key differentially expressed genes that potentially influence follicular hormone metabolism and growth, like ID2, CHRD, TGIF2 and MAD2L1, and constructed an interaction network between lncRNA transcripts and mRNAs. CONCLUSIONS: In summary, this study preliminarily revealed the differences in gene expression patterns among buffalo follicles of different sizes and their potential molecular regulatory mechanisms. It provides a new perspective for exploring the mechanism of buffalo follicular dominance and improving buffalo reproductive performance.

High-Quality Genomes of Pangolins: Insights into the Molecular Basis of Scale Formation and Adaption to Myrmecophagous Diet.

Pangolins are one of nature's most fascinating species being scales covered and myrmecophagous diet, yet relatively little is known about the molecular basis. Here, we combine the multi-omics, evolution, and fundamental proteins feature analysis of both Chinese and Malayan pangolins, highlighting the molecular mechanism of both myrmecophagous diet and scale formation, representing a fascinating evolutionary strategy to occupy the unique ecological niches. In contrast to conserved organization of epidermal differentiation complex, pangolin has undergone large scale variation and gene loss events causing expression pattern and function conversion that contribute to cornified epithelium structures on stomach to adapt myrmecophagous diet. Our assemblies also enable us to discover large copies number of high glycine-tyrosine keratin-associated proteins (HGT-KRTAPs). In addition, highly homogenized tandem array, amino content, and the specific expression pattern further validate the strong connection between the molecular mechanism of scale hardness and HGT-KRTAPs.

Deciphering the biodesulfurization pathway employing marine mangrove Bacillus aryabhattai strain NM1-A2 according to whole genome sequencing and transcriptome analyses.

In the biogeochemical cycle, sulfur oxidation plays a vital role and is typically referred to as the elemental sulfur or reductive sulfide oxidation process. This study aimed to characterize a subtropical mangrove-isolated bacterial strain using biochemical, whole-genome, and transcriptome sequencing analyses to enhance our understanding of sulfur metabolism and biodegradation from a molecular genetic perspective. Strain NM1-A2 was characterized as Gram-positive and found to have a close molecular phylogenetic relationship with Bacillus aryabhattai. NM1-A2 efficiently converted dibenzothiophene (DBT) into 2-hydroxybiphenyl (2-HBP) via a 4S pathway with 95% efficiency, using enzymes encoded by the dsz operon (dszA, dszB, and dszC), which determine monooxygenases (DszA & DszC) and desulfinase (DszB). The whole-genome sequence of NM1-A2 had a length of approximately 5,257,678 bp and included 16 sulfur metabolism-related genes, featuring the ABC transport system, small subunit (ssu) and cysteine (cys) gene families, and adenosine 5'-phosphosulfate (APS) and 3'-phosphoadenosine-5'-phosphosulfate (PAPS) biosynthesis-related genes. Transcriptomic analysis of NM1-A2 using three sulfur groups-magnesium sulfate (MS), sulfur powder (SP), and sodium thiosulfate (ST) resulted in a significant number of differentially expressed genes (1200, 2304, and 2001, respectively). This analysis revealed that intracellular cysteine concentration directly regulated the expression of cys and ssu genes. Sulfate did not directly affect cys gene expression but repressed ssu gene expression. The cys gene expression levels decreased during the conversion of sulfate to sulfide and cysteine. The transcriptomic data was validated by analyzing the expression patterns of NM1-A2 using real-time quantitative PCR validation analysis. The expression levels of cysl, mccB, and nrnA were significantly upregulated, while cysH, metB, and sat were downregulated in the SP, ST, and MS groups, respectively. This research contributes to our understanding of marine mangrove microorganisms' bacterial efficiency through characterization, whole-genome, and transcriptome sequencing-based molecular degradation of organic compounds in the mangrove ecosystem, which may enhance nutrient availability.

Dynamics of epigenetic regulation in Dryophytes versicolor skeletal muscle: Lysine methylation and acetylation involvement in metabolic rate depression.

For the breadth of the winter, Dryophytes versicolor can survive full body freezing utilizing a phenomenon known as metabolic rate depression (MRD). Epigenetic transcriptional control on gene expression, such as histone methylation and acetylation, can aid in implementing a balance between permissive and restricted chromatin required to endure this stress. As such, this study explores the interplay between histone lysine methyl and acetyl transferases (HKMTs, HATs), as well as the abundance of various acetyl-lysine and methyl-lysine moieties on histone H3 and H4. Results showing that overexpression of transcriptionally repressive marks, and under expression of active ones, suggest a negative effect on overall gene transcription in skeletal muscle tissue.

A Bibliometric Analysis of the 100 Most-Cited Articles on Otoplasty.

A bibliometric analysis was conducted in April 2024 to review the current trends in otoplasty. It involved a literature search of the Scopus database for original articles with the query terms "otoplasty" and "pinnaplasty," without restricting publication dates or selecting journals in the database. The top 100 articles with the highest citations were reviewed. Bibliometric analysis was performed with the Scimago journal impact factor. The screening was done following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to extract the top 100 most-cited articles in otoplasty. We excluded articles not focused on otoplasty, those involving other surgical procedures, and non-English articles. With Scopus and manual screening, we performed citation analysis of selected articles. Mean values were calculated for the number of citations and citations per year. Of the 951 studies identified, 100 (10.5%) were analyzed in detail. The studies were published between 1941 and 2024, with a mean of 36 ± 23.7 citations per paper. The journal Plastic and Reconstructive Surgery reported the highest number (23%, n = 23) of articles, followed by the Journal of Plastic, Reconstructive and Aesthetic Surgery with 13% (n = 13) articles. The highest number of articles originated from the United States (38%, n = 38), followed by the United Kingdom (15%, n = 15). Our bibliometric analysis provides a comprehensive overview of the landscape of otoplasty research, highlighting key publications, authors, and journals. This study contributes to the understanding of the evolution and impact of otoplasty literature, laying the groundwork for further research and innovation in this field.

The regulation of m6A-related proteins during whole-body freezing of the freeze-tolerant wood frog.

Rana sylvatica (also known as Boreorana sylvatica) is one of the few vertebrates that spend extreme winters showing no physiological signs of life. Up to 70% of the total body water of the wood frog freezes as extracellular ice. Survival in extreme conditions requires regulation at transcriptional and translational levels to activate prosurvival pathways. N6-methyladenosine (m6A) methylation is one of the most common RNA modifications, regulating transcript processing and translation by executing important functions that affect regulatory pathways in stress conditions. In the study, regulation of m6A-related proteins in the liver of R. sylvatica was analyzed during 24 h frozen and 8 h thaw conditions. Decreases in the activity of demethylases of 28.44 ± 0.4% and 24.1 ± 0.9% of control values in frozen and thaw tissues, respectively, were observed. Total protein levels of m6A methyltransferase complex components methyltransferase-like 14 and Wilm's tumor associated protein were increased by 1.28-fold and 1.42-fold, respectively, during freezing. Demethylase fat mass and obesity, however, showed a decreasing trend, with a significant decrease in abundance during recovery from frozen conditions. Levels of mRNA degraders YTHDF2 and YTHDC2 also decreased under stress. Overall, increased levels of m6A methylation complex components, and suppressed levels of readers/erasers, provide evidence for the potential role of RNA methylation in freezing survival and its regulation in a hypometabolic state.

The freezability of Mediterranean buffalo sperm is associated with lysine succinylation and lipid metabolism.

Semen cryopreservation is used for the propagation of variety among species and domestic breeding. Mitochondria are implicated in sperm freezability, and their proteins are prone to succinylation, but the relationship between sperm freezability and mitochondrial protein succinylation is unclear. In this study, six bulls were classified as having good or poor freezability ejaculates (GFE or PFE, each 3 bulls). The fresh sperm mitochondrial membrane potential (MMP) and pan succinylation level of the two groups were first detected. Then the lysine succinylome and fatty acid content of the two groups were analyzed using label-free LC-MS/MS and GC-MS/MS in multiple reaction monitoring (MRM) modes, respectively. The results indicated that the GFE sperm had significantly higher MMPs than the PFE group (p < 0.05). A total of 1393 succinylation sites corresponding to 426 proteins were assessed and 5 succinylated peptides of the GFE group were markedly upregulated, while 3 were significantly downregulated (FC > 2.0 - < 0.5 and p-value < 0.05) when compared to the PFE group. Forty-six succinylated proteins were identified to have consistent presence/absence expression. The upregulated succinylated proteins in the GFE sperm were enriched in lipid metabolic processes. A total of 31 fatty acids were further subjected to quantitative analysis of which 23 including arachidic (C20:0), linolenic (C18:3n3), and docosahexaenoic acids (C22:6n3) were decreased in GFE sperm when compared with PFE (p < 0.05). These results suggest that lysine succinylation can potentially influence the sperm freezability of Mediterranean buffaloes through mitochondrial lipid metabolism. This novel study provides our understanding of sperm succinylation and the molecular basis for the mechanism of sperm freezability.

Role of FOXO transcription factors in the tolerance of whole-body freezing in the wood frog, Rana sylvatica.

The wood frog (Rana Sylvatica) can endure the sub-zero temperatures of winter by freezing up to 65% of total body water as extracellular ice and retreating into a prolonged hypometabolic state. Freeze survival requires the coordination of various adaptations, including a global suppression of metabolic functions and select activation of pro-survival genes. Transcription factors playing roles in metabolism, stress tolerance, and cell proliferation may assist in making survival in a frozen state possible. In this study, the role of Forkhead box 'other' (FOXO) transcription factors in freeze tolerance, and related changes to the insulin pathway, are investigated. Immunoblotting was used to assess total and phosphorylated amounts of FOXO proteins in wood frogs subjected to freezing for 24 h and thawed recovery for 8 h. Levels of active FOXO3 increased in brain, kidney, and liver during freezing and thawing, suggesting a need to maintain or enhance antioxidant defenses under these stresses. Results implicate FOXO involvement in the metabolic regulation of natural freeze tolerance.

Exploring the Therapeutic Potential of Traditional Antimalarial and Antidengue Plants: A Mechanistic Perspective.

Malaria, a highly perilous infectious disease, impacted approximately 230 million individuals globally in 2019. Mosquitoes, vectors of over 10% of worldwide diseases, pose a significant public health menace. The pressing need for novel antimalarial drugs arises due to the imminent threat faced by nearly 40% of the global population and the escalating resistance of parasites to current treatments. This study comprehensively addresses prevalent parasitic and viral illnesses transmitted by mosquitoes, leading to the annual symptomatic infections of 400 million individuals, placing 100 million at constant risk of contracting these diseases. Extensive investigations underscore the pivotal role of traditional plants as rich sources for pioneering pharmaceuticals. The latter half of this century witnessed the ascent of bioactive compounds within traditional medicine, laying the foundation for modern therapeutic breakthroughs. Herbal medicine, notably influential in underdeveloped or developing nations, remains an essential healthcare resource. Traditional Indian medical systems such as Ayurveda, Siddha, and Unani, with a history of successful outcomes, highlight the potential of these methodologies. Current scrutiny of Indian medicinal herbs reveals their promise as cutting-edge drug reservoirs. The propensity of plant-derived compounds to interact with biological receptors positions them as prime candidates for drug development. Yet, a comprehensive perspective is crucial. While this study underscores the promise of plant-based compounds as therapeutic agents against malaria and dengue fever, acknowledging the intricate complexities of drug development and the challenges therein are imperative. The journey from traditional remedies to contemporary medical applications is multifaceted and warrants prudent consideration. This research aspires to offer invaluable insights into the management of malaria and dengue fever. By unveiling plant-based compounds with potential antimalarial and antiviral properties, this study aims to contribute to disease control. In pursuit of this goal, a thorough understanding of the mechanistic foundations of traditional antimalarial and antidengue plants opens doors to novel therapeutic avenues.

Genomic analysis of arginine vasopressin gene in riverine buffalo reveals its potential association with silent estrus behavior.

BACKGROUND: Poor estrus expression behavior causes suboptimal reproductive efficiency through poor conception rate. Various signaling pathways are involved in estrus expression but arginine vasopressin (AVP) gene with oxytocin predominantly regulates estrus behavior. This study aimed to perform genomic characterization and evolutionary dynamics of AVP gene through association testing of the novel polymorphic loci and comparative genomic analysis to explore the potential effect of AVP gene on estrus behavior of Nili-Ravi buffaloes. METHODS AND RESULTS: 198 Nili-Ravi buffaloes were screened for the quest of novel polymorphism in the AVP gene. In exon-1, five polymorphic sites were detected including deletion of two (c.47delA and c.57delA) nucleotides that caused drastic variation in subsequent amino acid sequence due to frame shift including functional short peptide of nine residues. The 3-D structure revealed a loss of transmembrane loop between 16 and 31 residues in Nili-Ravi buffalo AVP protein sequence, suggesting that missing loop apparently reduced the gene functionality in Nili-Ravi buffalo by inhibiting cellular reactions and muting the animal estrus cyclicity. Three polymorphisms detected in AVP gene were significantly associated with silent estrus (P < 0.05). The comparative genomic analysis revealed that AVP gene is present on chromosome 14 having one conserved motif (Neurohypophysial) in buffalo. CONCLUSIONS: This study suggested the potential use of polymorphic sites as promising genetic markers for selection of buffaloes with pronounced estrus expression.

Proteomic analysis identifies potential markers in small white and small yellow follicle development in chickens.

Extensive knowledge of follicular development is imperative for improving egg production in chickens. The functional role of follicles to produce oocytes (eggs) is well recognised; however, specific markers associated with follicle development have been poorly explored. Therefore, a tandem mass tag based proteomic technique was used to identify the status of the proteome of small white follicles (1-4mm) and small yellow follicles (6-8mm). Analysis of differentially expressed proteins (DEP, Fold Change>1.2, P -value<0.05) demonstrated a total of 92 proteins (n =92), of which 35 (n =35) were upregulated and 57 were downregulated. DEP were further used for gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathways. The GO analysis found that DEP were mainly associated with the RNA metabolic process, cellular component organisation, peptide biosynthetic process and protein folding, thereby suggesting a key role in the follicle development process. Kyoto Encyclopedia of Genes and Genomes enrichment pathway analysis of the DEP substantiated the findings of GO analysis and described that DEP are involved in regulation of the cytoskeleton, carbon metabolism and amino acid biosynthesis. The validation of proteomic data through real-time quantitative polymerase chain reaction suggested HSPA8, HSPA2, SOD1 and FKPB3 as potential markers of small white and small yellow follicle development. This study demonstrates an understanding of proteome dynamics and represents the most comprehensive information on the entire Guangxi Ma chicken follicular proteome.

Effect of environmental temperature on semen quality and seminal plasma metabolites of Mediterranean buffalo bulls.

High-quality semen with high viability is critical to improving the in-vitro fertilization efficiency. This study aimed to understand the effect of ambient temperature and humidity on semen quality and seminal plasma biochemical parameters of Mediterranean buffalo in March and July. The metabolites of seminal plasma in two seasons were detected using the UPLC-MS/MS method. The results showed that temperature and humidity index (THI) in March were 66.86 ± 2.98, and 82.94 ± 3.52 in July. Compared with in March, breath frequency, rectal temperature, and heat shock protein 70 expressions of seminal plasma were significantly increased in July (p < 0.05), motility of sperm was dramatically reduced, and sperm deformity rate was significantly increased (p < 0.05). Fructose, acid phosphatase and α-glucosidase in seminal plasma were significantly increased (p < 0.05) in July, while testosterone level was significantly reduced (p < 0.05). Six different metabolites were found in the two groups, which involved in three metabolic pathways, the tricarboxylic acid cycle, glycerophospholipid, glyoxylic acid and dicarboxylic acid. The above results indicate that the increased ambient temperature has obvious side effects on the semen quality of Mediterranean buffalo, and the compromised quality is associated with the change of metabolites related to male hormone secretion, energy metabolism and fatty acid oxidation.

Efficient Top-K Identical Frequent Itemsets Mining without Support Threshold Parameter from Transactional Datasets Produced by IoT-Based Smart Shopping Carts.

Internet of Things (IoT)-backed smart shopping carts are generating an extensive amount of data in shopping markets around the world. This data can be cleaned and utilized for setting business goals and strategies. Artificial intelligence (AI) methods are used to efficiently extract meaningful patterns or insights from such huge amounts of data or big data. One such technique is Association Rule Mining (ARM) which is used to extract strategic information from the data. The crucial step in ARM is Frequent Itemsets Mining (FIM) followed by association rule generation. The FIM process starts by tuning the support threshold parameter from the user to produce the number of required frequent patterns. To perform the FIM process, the user applies hit and trial methods to rerun the aforesaid routine in order to receive the required number of patterns. The research community has shifted its focus towards the development of top-K most frequent patterns not using the support threshold parameter tuned by the user. Top-K most frequent patterns mining is considered a harder task than user-tuned support-threshold-based FIM. One of the reasons why top-K most frequent patterns mining techniques are computationally intensive is the fact that they produce a large number of candidate itemsets. These methods also do not use any explicit pruning mechanism apart from the internally auto-maintained support threshold parameter. Therefore, we propose an efficient TKIFIs Miner algorithm that uses depth-first search strategy for top-K identical frequent patterns mining. The TKIFIs Miner uses specialized one- and two-itemsets-based pruning techniques for topmost patterns mining. Comparative analysis is performed on special benchmark datasets, for example, Retail with 16,469 items, T40I10D100K and T10I4D100K with 1000 items each, etc. The evaluation results have proven that the TKIFIs Miner is at the top of the line, compared to recently available topmost patterns mining methods not using the support threshold parameter.

Ameliorating Effects of TRIM67 against Intestinal Inflammation and Barrier Dysfunction Induced by High Fat Diet in Obese Mice.

Tripartite Motif 67 (TRIM67) is an important member of TRIM family proteins, which participates in different cellular processes including immune response, proliferation, differentiation, carcinogenesis, and apoptosis. In recent years, a high fat diet (HFD) has remained one of the main causes of different metabolic diseases and increases in intestinal permeability as well as inducing intestinal inflammation. The current study investigated the protective effects of TRIM67 in the ileum and colon of obese mice. 4-week-old wild-type (WT) C57BL/6N mice and TRIM67 knockout (KO) C57BL/6N mice were selected and randomly divided into four sub-groups, which were fed with control diet (CTR) or HFD for 14 weeks. Samples were collected at the age of 18 weeks for analysis. To construct an in vitro obesity model, over-expressed IPEC-J2 cells (porcine intestinal cells) with Myc-TRIM67 were stimulated with palmitic acid (PA), and its effects on the expression level of TRM67, inflammatory cytokines, and barrier function were evaluated. The KO mice showed pathological lesions in the ileum and colon and this effect was more obvious in KO mice fed with HFD. In addition, KO mice fed with a HFD or CTR diet had increased intestinal inflammation, intestinal permeability, and oxidative stress compared to that WT mice fed with these diets, respectively. Moreover, IPEC-J2 cells were transfected with TRIM67 plasmid to perform the same experiments after stimulation with PA, and the results were found consistent with the in vivo evaluations. Taken together, our study proved for the first time that HFD and TRIM67 KO mice have synergistic damaging effects on the intestine, while TRIM67 plays an important protective role in HFD-induced intestinal damage.

Mainstem Bronchial Diameters and Dimensions in Infants and Children: A Systematic Review of the Literature.

Anatomic measurements of the right (RMB) and left mainstem bronchi (LMB) in infants and children have been accomplished using various modalities. The objective of the present review was to determine whether enough data were available to provide standardized lower airway dimensions in the pediatric population. For the present study, 12 studies with data of the lower pediatric airway dimensions of 1,611 children published from 1923-2020 were reviewed and analyzed. The eligible criteria included studies measuring lower airway dimensions in the pediatric population. Various techniques were used for airway measurement, with computed tomography studies being most abundant. There was a progressive increase in the size of RMB and LMB with age, with a close approximation of the LMB-to-RMB ratio across all studies. In children younger than 1 year old, the RMB and LMB diameters were between 4 and 5 mm and 3 and 5 mm, respectively. Overall, there was significant variation in the methods and modality used to obtain measurements, and therefore it was difficult to establish standardized lower airway dimensions in the pediatric population. Additional homogeneous data with standardized measurement techniques and modalities across different pediatric age groups are needed to define these dimensions further. Such data may be helpful in designing airway equipment, lung isolation devices, and airway stents.

Point-of-care ultrasound to confirm endotracheal tube cuff position in relationship to the cricoid in the pediatric population.

BACKGROUND: Anatomically, the subglottic area and the cricoid ring are the narrowest portions of the larynx. To limit the potential for damage related to mucosal pressure injuries from the presence of an endotracheal tube, the cuff should be placed below the cricoid in children. Previously, no clinical or imaging method has been used in real time to determine the exact location of the endotracheal tube cuff after endotracheal intubation. Point-of-care ultrasound may provide an option as a safe and rapid means of visualizing the endotracheal tube cuff and its relationship to the cricoid ring thereby achieving ideal endotracheal tube cuff positioning-below the cricoid. METHODS: In this prospective, nonrandomized trial, point-of-care ultrasound was used following endotracheal intubation in children to evaluate the position of the endotracheal tube cuff in relationship to the cricoid and tracheal rings. After anesthesia was induced and the trachea was intubated, the endotracheal tube cuff and its position in relation to the cricoid and tracheal rings were identified in the longitudinal plane using point-of-care ultrasound. With the patient's neck in a neutral position, the level of the proximal (cephalad) margin of the saline-filled cuff of the endotracheal tube was identified and recorded in relationship to the cricoid and tracheal rings. The ideal position is defined as the cephalad margin of the endotracheal tube cuff below the level of the cricoid. RESULTS: The study cohort included 80 patients, ranging in age from 1 to 78 months. In all patients, the cuff of the ETT, cricoid, and tracheal rings were identified. The cephalad end of the endotracheal tube cuff was found at the level of the cricoid in 16.3% of patients, at the first tracheal ring in 27.5% of patients, at the second tracheal ring in 23.8% of patients, at the third tracheal ring in 17.5% of patients, and at below the fourth tracheal ring in 15% of patients. Initial endotracheal tube cuff position had no significant association with age, height, weight, endotracheal tube size, and endotracheal tube type. CONCLUSION: Point-of-care ultrasound provides a rapid and effective means of identifying the position of the endotracheal tube cuff in relationship to the cricoid ring. The technique may have applications in the perioperative arena, emergency departments, and intensive care units.

Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Energy Homeostasis of Dairy Animals: Exploiting Their Modulation through Nutrigenomic Interventions.

Peroxisome proliferator-activated receptors (PPARs) are the nuclear receptors that could mediate the nutrient-dependent transcriptional activation and regulate metabolic networks through energy homeostasis. However, these receptors cannot work properly under metabolic stress. PPARs and their subtypes can be modulated by nutrigenomic interventions, particularly under stress conditions to restore cellular homeostasis. Many nutrients such as polyunsaturated fatty acids, vitamins, dietary amino acids and phytochemicals have shown their ability for potential activation or inhibition of PPARs. Thus, through different mechanisms, all these nutrients can modulate PPARs and are ultimately helpful to prevent various metabolic disorders, particularly in transition dairy cows. This review aims to provide insights into the crucial role of PPARs in energy metabolism and their potential modulation through nutrigenomic interventions to improve energy homeostasis in dairy animals.

Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders.

In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer-both in vivo and in vitro clinical trials-has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.

Fatty acid biosynthesis and transcriptional regulation of Stearoyl-CoA Desaturase 1 (SCD1) in buffalo milk.

BACKGROUND: Buffalo milk is considered as a highly nutritious food owing to its higher contents of fatty acids (FA) and rich nutrient profile. Higher fat contents of buffalo milk make it suitable for processing to develop various healthy and nutritious products. Moreover, buffalo milk contains more unsaturated FAs (UFA) such as oleic and linolenic acid, which are important from the human health point of view owing to their desirable physiological effects. However, inadequate information is available about the chemical composition and mechanism of FA synthesis in buffalo milk. In this study, we hypothesized that expression of SCD1 gene could alter the biosynthesis of FA in epithelial cells of mammary gland and subsequently affect the FA contents in buffalo milk. We investigated the transcriptional and biological role of Stearoyl-CoA Desaturase 1 (SCD1) in the buffalo mammary epithelial cells (BMECs) during FA and triacylglycerol (TAG) synthesis. RESULTS: Results revealed that unsaturated fatty acid contents were much higher in concentration in buffalo milk as compared to Holstein cow. Significant increase in the expression level of FAS, ACACA, SREBP1, PPARG, GPAT, and AGPAT genes was observed in response to altered expression of SCD1 in buffalo milk. Moreover, change in SCD1 gene in BMECs also mediated the expression of genes related to FA biosynthesis subsequently leading to alter the FA composition. Overexpression of SCD1 significantly increased the expression of genes associated with FA and TAG synthesis leading to enhance FA and unsaturated FA contents in BMECs. However, down-regulation of SCD1 exhibited opposite consequences. CONCLUSION: Our study provides mechanistic insights on transcriptional regulation of SCD1 to alter FA and TAG synthesis through directly or indirectly mediating biosynthesis and metabolic pathways in BMECs. We provide preliminary findings regarding engineering of FA contents in buffalo milk through SCD1 signaling.

Socio-religious Prognosticators of Psychosocial Burden of Beta Thalassemia Major.

The study investigates the socio-religious factors in the propagation of genetically inherited disease of Beta thalassemia. The disorder which reportedly has a significant protraction through repeated cousin marriages results in the social maladjustment of the parents of the sick children due to constant depression, anxiety, and weak social interaction and may lead to social isolation as well. This research aims to find out the significant effect of socio-religious trends on psychosocial burden of beta thalassemia major among cousin and non-cousin couples in the province of Punjab in Pakistan. It takes a sample of 932 parents of sick children, among whom 735 were married with cousins and 197 with non-cousins, for data collection. The findings reveal that inadequate knowledge of the disease, insufficient or misdirected social support, stigmatization, and marriage breakups caused by the disease, superstitions, and misinterpretations of religion and the subsequent practices accordingly as significant predictors of psychosocial burden of beta thalassemia major among non-cousins and cousin couples. Additionally, it also finds patriarchy as only significant predictors of outcome variable among cousin couples.