Miracle-dz/UniFAR-FTUs huggingface dataset:
PROTECTIVE ACTIVITY OF ETHANOLIC EXTRACT OF AMORPHOPHALLUS CAMPANULATUS AGAINST ETHANOL INDUCED HEPATOTOXICITY IN RATS

Objective: The present study was aimed to evaluate the protective role of ethanolic extract of Amorphophallus campanulatus Roxb. tubers against ethanol‐induced hepatotoxicity in rats. Methods: Adult male albino Wistar rats, weighing 150‐200g, were randomized into control and experimental group. Test group of animals were treated with ethanol (2gm/kg body wt for 30 days). Silymarin was used as a standard reference. Ethanolic extract of Amorphophallus campanulatus (250 mg/kg body wt and 500 mg/kg body wt) were administered to the ethanol treated rats simultaneously for thirty days. The extract at these two doses were also administered to the animals separately to study the presence of any harmful effect on the liver function. Results: Administration of ethanolic extract of Amorphophallus campanulatus at two different doses significantly normalized the values of SOD, CAT, GSH and TBARS. The elevated serum enzymatic levels of AST, ALT, ALP and total protein were significantly restored towards normal by pre‐treatment with ethanolic extract of Amorphophallus campanulatus (p<0.001). However, no significant alteration in the liver marker enzymes and the antioxidant markers in liver tissue was observed in the only extract treated groups when compared to control, indicating their non-toxic nature. There was also no significant dose dependent variation observed when treated with two different concentrations of the extract. Histopathological studies also confirmed the hepatoprotective nature of the extracts by normalizing the hepato-cellular architecture like that of normal in the treated groups when compared to the only ethanol administered group. Conclusion: The results of this study strongly indicate that ethanolic extract of Amorphophallus campanulatus has potent hepatoprotective action against ethanol induced hepatic damage particularly by scavenging free radicals and combating oxidative stress. Further investigation can lead to the development of phytomedicines of therapeutic significance against oxidative stress.
Tunable Electronic Properties of Lateral Monolayer Transition Metal Dichalcogenide Superlattice Nanoribbons

The structural stability and structural and electronic properties of lateral monolayer transition metal chalcogenide superlattice zigzag and armchair nanoribbons have been studied by employing a first-principles method based on the density functional theory. The main focus is to study the effects of varying the width and periodicity of nanoribbon, varying cationic and anionic elements of superlattice parent compounds, biaxial strain, and nanoribbon edge passivation with different elements. The band gap opens up when the (MoS2)3/(WS2)3 and (MoS2)3/(MoTe2)3 armchair nanoribbons are passivated by H, S and O atoms. The H and O co-passivated (MoS2)3/(WS2)3 armchair nanoribbon exhibits higher energy band gap. The band gap with the edge S vacancy connecting to the W atom is much smaller than the S vacancy connecting to the Mo atom. Small band gaps are obtained for both edge and inside Mo vacancies. There is a clear difference in the band gap states between inside and edge Mo vacancies for symmetric nanoribbon structure, while there is only a slight difference for asymmetric structure. The electronic orbitals of atoms around Mo vacancy play an important role in determining the valence band maximum, conduction band minimum, and impurity level in the band gap.
Organ Fibrosis and Autoimmunity: The Role of Inflammation in TGFβ-Dependent EMT

Recent advances in our understanding of the molecular pathways that control the link of inflammation with organ fibrosis and autoimmune diseases point to the epithelial to mesenchymal transition (EMT) as the common association in the progression of these diseases characterized by an intense inflammatory response. EMT, a process in which epithelial cells are gradually transformed to mesenchymal cells, is a major contributor to the pathogenesis of fibrosis. Importantly, the chronic inflammatory microenvironment has emerged as a decisive factor in the induction of pathological EMT. Transforming growth factor-β (TGF-β), a multifunctional cytokine, plays a crucial role in the induction of fibrosis, often associated with chronic phases of inflammatory diseases, contributing to marked fibrotic changes that severely impair normal tissue architecture and function. The understanding of molecular mechanisms underlying EMT-dependent fibrosis has both a basic and a translational relevance, since it may be useful to design therapies aimed at counteracting organ deterioration and failure. To this end, we reviewed the recent literature to better elucidate the molecular response to inflammatory/fibrogenic signals in autoimmune diseases in order to further the specific regulation of EMT-dependent fibrosis in more targeted therapies.
Fuzzy Decision-Based Efficient Task Offloading Management Scheme in Multi-Tier MEC-Enabled Networks

Multi-access edge computing (MEC) is a new leading technology for meeting the demands of key performance indicators (KPIs) in 5G networks. However, in a rapidly changing dynamic environment, it is hard to find the optimal target server for processing offloaded tasks because we do not know the end users’ demands in advance. Therefore, quality of service (QoS) deteriorates because of increasing task failures and long execution latency from congestion. To reduce latency and avoid task failures from resource-constrained edge servers, vertical offloading between mobile devices with local-edge collaboration or with local edge-remote cloud collaboration have been proposed in previous studies. However, they ignored the nearby edge server in the same tier that has excess computing resources. Therefore, this paper introduces a fuzzy decision-based cloud-MEC collaborative task offloading management system called FTOM, which takes advantage of powerful remote cloud-computing capabilities and utilizes neighboring edge servers. The main objective of the FTOM scheme is to select the optimal target node for task offloading based on server capacity, latency sensitivity, and the network’s condition. Our proposed scheme can make dynamic decisions where local or nearby MEC servers are preferred for offloading delay-sensitive tasks, and delay-tolerant high resource-demand tasks are offloaded to a remote cloud server. Simulation results affirm that our proposed FTOM scheme significantly improves the rate of successfully executing offloaded tasks by approximately 68.5%, and reduces task completion time by 66.6%, when compared with a local edge offloading (LEO) scheme. The improved and reduced rates are 32.4% and 61.5%, respectively, when compared with a two-tier edge orchestration-based offloading (TTEO) scheme. They are 8.9% and 47.9%, respectively, when compared with a fuzzy orchestration-based load balancing (FOLB) scheme, approximately 3.2% and 49.8%, respectively, when compared with a fuzzy workload orchestration-based task offloading (WOTO) scheme, and approximately 38.6%% and 55%, respectively, when compared with a fuzzy edge-orchestration based collaborative task offloading (FCTO) scheme.
Targeting Mitochondria by SS-31 Ameliorates the Whole Body Energy Status in Cancer- and Chemotherapy-Induced Cachexia

Simple Summary Cancer cachexia is a debilitating syndrome, caused by both tumor growth and chemotherapy. The skeletal muscle is one of the main tissues affected during cachexia, presenting with altered metabolism and function, leading to progressive tissue wasting. In the current study we aimed at counteracting cachexia by pharmacologically improving metabolic function with the mitochondria-targeted compound SS-31. Experimental cancer cachexia was obtained using C26-bearing mice either receiving chemotherapy (oxaliplatin plus 5-fluorouracil) or not. SS-31 proved effective in rescuing some of the metabolic impairments imposed by both tumor and chemotherapy in the skeletal muscle and the liver, improving systemic energy control. Unfortunately, such effects were no longer present at late disease stages when refractory cachexia ensued. Overall, we provide evidence of potential new treatments targeting mitochondrial function in order to counteract or delay cancer cachexia. Abstract Objective: Cachexia is a complex metabolic syndrome frequently occurring in cancer patients and exacerbated by chemotherapy. In skeletal muscle of cancer hosts, reduced oxidative capacity and low intracellular ATP resulting from abnormal mitochondrial function were described. Methods: The present study aimed at evaluating the ability of the mitochondria-targeted compound SS-31 to counteract muscle wasting and altered metabolism in C26-bearing (C26) mice either receiving chemotherapy (OXFU: oxaliplatin plus 5-fluorouracil) or not. Results: Mitochondrial dysfunction in C26-bearing (C26) mice associated with alterations of cardiolipin fatty acid chains. Selectively targeting cardiolipin with SS-31 partially counteracted body wasting and prevented the reduction of glycolytic myofiber area. SS-31 prompted muscle mitochondrial succinate dehydrogenase (SDH) activity and rescued intracellular ATP levels, although it was unable to counteract mitochondrial protein loss. Progressively increased dosing of SS-31 to C26 OXFU mice showed transient (21 days) beneficial effects on body and muscle weight loss before the onset of a refractory end-stage condition (28 days). At day 21, SS-31 prevented mitochondrial loss and abnormal autophagy/mitophagy. Skeletal muscle, liver and plasma metabolomes were analyzed, showing marked energy and protein metabolism alterations in tumor hosts. SS-31 partially modulated skeletal muscle and liver metabolome, likely reflecting an improved systemic energy homeostasis. Conclusions: The results suggest that targeting mitochondrial function may be as important as targeting protein anabolism/catabolism for the prevention of cancer cachexia. With this in mind, prospective multi-modal therapies including SS-31 are warranted.
Heme Oxygenase 1: A Defensive Mediator in Kidney Diseases

The incidence of kidney disease is rising, constituting a significant burden on the healthcare system and making identification of new therapeutic targets increasingly urgent. The heme oxygenase (HO) system performs an important function in the regulation of oxidative stress and inflammation and, via these mechanisms, is thought to play a role in the prevention of non-specific injuries following acute renal failure or resulting from chronic kidney disease. The expression of HO-1 is strongly inducible by a wide range of stimuli in the kidney, consequent to the kidney’s filtration role which means HO-1 is exposed to a wide range of endogenous and exogenous molecules, and it has been shown to be protective in a variety of nephropathological animal models. Interestingly, the positive effect of HO-1 occurs in both hemolysis- and rhabdomyolysis-dominated diseases, where the kidney is extensively exposed to heme (a major HO-1 inducer), as well as in non-heme-dependent diseases such as hypertension, diabetic nephropathy or progression to end-stage renal disease. This highlights the complexity of HO-1’s functions, which is also illustrated by the fact that, despite the abundance of preclinical data, no drug targeting HO-1 has so far been translated into clinical use. The objective of this review is to assess current knowledge relating HO-1’s role in the kidney and its potential interest as a nephroprotection agent. The potential therapeutic openings will be presented, in particular through the identification of clinical trials targeting this enzyme or its products.
Pancytopenia, Recurrent Infection, Poor Wound Healing, Heterotopia of the Brain Probably Associated with A Candidate Novel de Novo CDC42 Gene Defect: Expanding the Molecular and Phenotypic Spectrum

CDC42 (cell division cycle protein 42) belongs to the Rho GTPase family that is known to control the signaling axis that regulates several cellular functions, including cell cycle progression, migration, and proliferation. However, the functional characterization of the CDC42 gene in mammalian physiology remains largely unclear. Here, we report the genetic and functional characterization of a non-consanguineous Saudi family with a single affected individual. Clinical examinations revealed poor wound healing, heterotopia of the brain, pancytopenia, and recurrent infections. Whole exome sequencing revealed a de novo missense variant (c.101C > A, p.Pro34Gln) in the CDC42 gene. The functional assays revealed a substantial reduction in the growth and motility of the patient cells as compared to the normal cells control. Homology three-dimensional (3-D) modeling of CDC42 revealed that the Pro34 is important for the proper protein secondary structure. In conclusion, we report a candidate disease-causing variant, which requires further confirmation for the etiology of CDC42 pathogenesis. This represents the first case from the Saudi population. The current study adds to the spectrum of mutations in the CDC42 gene that might help in genetic counseling and contributes to the CDC42-related genetic and functional characterization. However, further studies into the molecular mechanisms that are involved are needed in order to determine the role of the CDC42 gene associated with aberrant cell migration and immune response.
Human Epidermal Growth Factor Receptor-3 Expression Is Regulated at Transcriptional Level in Breast Cancer Settings by Junctional Adhesion Molecule-A via a Pathway Involving Beta-Catenin and FOXA1

Simple Summary Signaling from the human epidermal growth factor receptor (HER) family of proteins increases in many cancers, including breast. HER2-high breast cancers are successfully treated with anti-HER2 therapies, but these drugs are limited by the fact that patients frequently develop resistance to them. One common mechanism by which resistance develops is when tumors acquire high levels of a family member called HER3. We had previously shown that a protein called JAM-A regulates the level of HER2 in breast cancer cells, and is associated with the development of resistance to HER2-targeted therapies. In this study we show for the first time that JAM-A levels also regulate those of HER3. Using breast cancer cell and tissue models and culminating in patient tissue material, we provide evidence that JAM-A regulates HER3 expression via a pathway involving the transcription factors β-catenin and FOXA1. We suggest that JAM-A merits future investigation as a novel drug target for its potential to reduce HER3 tumorigenic signaling and to offset the development of resistance to HER2-targeted therapies. Abstract The success of breast cancer therapies targeting the human epidermal growth factor receptor-2 (HER2) is limited by the development of drug resistance by mechanisms including upregulation of HER3. Having reported that HER2 expression and resistance to HER2-targeted therapies can be regulated by Junctional Adhesion Molecule-A (JAM-A), this study investigated if JAM-A regulates HER3 expression. Expressional alteration of JAM-A in breast cancer cells was used to test expressional effects on HER3 and its effectors, alongside associated functional behaviors, in vitro and semi-in vivo. HER3 transcription factors were identified and tested for regulation by JAM-A. Finally a patient tissue microarray was used to interrogate connections between putative pathway components connecting JAM-A and HER3. This study reveals for the first time that HER3 and its effectors are regulated at gene/protein expression level by JAM-A in breast cancer cell lines; with functional consequences in in vitro and semi-in vivo models. In bioinformatic, cellular and patient tissue models, this was associated with regulation of the HER3 transcription factor FOXA1 by JAM-A via a pathway involving β-catenin. Our data suggest a novel model whereby JAM-A expression regulates β-catenin localization, in turn regulating FOXA1 expression, which could drive HER3 gene transcription. JAM-A merits investigation as a novel target to prevent upregulation of HER3 during the development of resistance to HER2-targeted therapies, or to reduce HER3-dependent tumorigenic signaling.
The Effects of Mechanical Scale on Neural Control and the Regulation of Joint Stability

Recent work has demonstrated how the size of an animal can affect neural control strategies, showing that passive viscoelastic limb properties have a significant role in determining limb movements in small animals but are less important in large animals. We extend that work to consider effects of mechanical scaling on the maintenance of joint integrity; i.e., the prevention of aberrant contact forces within joints that might lead to joint dislocation or cartilage degradation. We first performed a literature review to evaluate how properties of ligaments responsible for joint integrity scale with animal size. Although we found that the cross-sectional area of the anterior cruciate ligament generally scaled with animal size, as expected, the effects of scale on the ligament’s mechanical properties were less clear, suggesting potential adaptations in passive contributions to the maintenance of joint integrity across species. We then analyzed how the neural control of joint stability is altered by body scale. We show how neural control strategies change across mechanical scales, how this scaling is affected by passive muscle properties and the cost function used to specify muscle activations, and the consequences of scaling on internal joint contact forces. This work provides insights into how scale affects the regulation of joint integrity by both passive and active processes and provides directions for studies examining how this regulation might be accomplished by neural systems.
Polymorphism of PvuII, Xba1, and SNP 12 Estrogen Receptor 1 (ESR1) in Hipospadias Patients at Tertiary Hospital Center

Introduction The prevalence of hypospadias ranges between 1: 250 to 300 per live birth. Estrogen exposure has been associated with the increasing incidence of hypospadias in humans and a significant relationship between Estrogen Receptor 1 (ESR1) polymorphisms and hypospadias was determined from the previous study. This study aims to determine the proportion of ESR1 polymorphism. Methods This was a descriptive study aimed to find the incidence of ESR1 gene polymorphism in hypospadias patients visiting the Urology Outpatient Unit of the Hasan Sadikin Bandung Hospital who will undergo hypospadias surgery. Deoxyribonucleic acid (DNA) was performed using foreskin of hypospadias patient during the surgery then being extracted and will be analyzed using polymerase chain reaction (PCR) sequencing. Results Thirty eight samples of hypospadias were identified, 5 samples were unable to sequence and 33 samples were successfully sequenced using the PCR method. The Pvull ESR1 gene was dominated by the T allele which is a wild-type allele and the genotype containing the T allele, namely TT + TC (57,2%). Normal genotype (TT) were more frequent in distal hypospadias, and Heterozygous polymorphisms (TC) was higher in proximal hypospadias. The ESR1 Xba1 gene polymorphism was dominated by the A allele which is a wild-type allele and the AA + AG genotype (76,1%). Normal genotype (AA) was more frequent in distal hypospadias, and both heterozygous hypospadias (AG) and homozygous hypospadias (GG) were found only in proximal hypospadias. The ESR1 SNP 12 gene polymorphisms were found in the combination of genotypes that played a role, namely GA + AA (81%) and the G allele which is a wild-type allele. Heterozygous polymorphisms (GA) was the most finding genotype and more frequent in proximal hypospadias. Conclusion ESR1 gene polymorphisms (PvuII, XbaI, and SNP 12) were found in hypospadias patients. ESR1 polymorphisms may correlate with the severity of hypospadias. Further research with a larger sample and better hypospadias grouping is needed to confirm.
Microbiome and PCOS: State-of-Art and Future Aspects

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract microbiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid.
Application of Olive By-Products in Livestock with Emphasis on Small Ruminants: Implications on Rumen Function, Growth Performance, Milk and Meat Quality

Simple Summary Olive oil is one of the main components in the Mediterranean diet that is known worldwide for its beneficial effects on human health due to its high content of monounsaturated fatty acids (MUFAs). During its extraction, a great quantity of olive by-products (OB) is generated that poses a risk to the environment due to its high organic load. Utilization of OB as a part of the ruminants’ diet could minimize the costs related to animal feeding and OB management and contribute to the preservation of natural resources. At the same time, their application in ruminants’ nutrition enables the sustainable use of high-added value bioactive ingredients inside food chains that improve milk and meat quality characteristics and fortify consumer health, without negative effects on rumen function, metabolism and productivity. Abstract The olive oil industry has a leading position in the Mediterranean countries, resulting in the production of considerable quantities of the respective by-products (OB) that constitute an important environmental issue. OB contain valuable nutrients and bioactive components that can be re-used under the bioeconomy strategy, and several chemical, physical, and biological processes have been evaluated with the intention to improve their nutritional value. One feasible application of OB is their incorporation in the diets of livestock and especially ruminants due to their high fiber content. As indicated by numerous studies, OB dietary supplementation increases the levels of monounsaturated fatty acids (MUFAs) and decreases that of saturated fatty acids (SFAs) in the milk and meat of ruminants with beneficial effects for consumers’ health. At the same time, environmental impact and feeding costs are reduced without detrimental effects on ruminal fermentation, nutrients utilization, growth performance, carcass traits, milk yield and composition.