O-GlcNAcylation controls pro-fibrotic transcriptional regulatory signaling in myofibroblasts.

Tissue injury causes activation of mesenchymal lineage cells into wound-repairing myofibroblasts (MFs), whose uncontrolled activity ultimately leads to fibrosis. Although this process is triggered by deep metabolic and transcriptional reprogramming, functional links between these two key events are not yet understood. Here, we report that the metabolic sensor post-translational modification O-linked ß-D-N-acetylglucosaminylation (O-GlcNAcylation) is increased and required for myofibroblastic activation. Inhibition of protein O-GlcNAcylation impairs archetypal myofibloblast cellular activities including extracellular matrix gene expression and collagen secretion/deposition as defined in vitro and using ex vivo and in vivo murine liver injury models. Mechanistically, a multi-omics approach combining proteomic, epigenomic, and transcriptomic data mining revealed that O-GlcNAcylation controls the MF transcriptional program by targeting the transcription factors Basonuclin 2 (BNC2) and TEA domain transcription factor 4 (TEAD4) together with the Yes-associated protein 1 (YAP1) co-activator. Indeed, inhibition of protein O-GlcNAcylation impedes their stability leading to decreased functionality of the BNC2/TEAD4/YAP1 complex towards promoting activation of the MF transcriptional regulatory landscape. We found that this involves O-GlcNAcylation of BNC2 at Thr455 and Ser490 and of TEAD4 at Ser69 and Ser99. Altogether, this study unravels protein O-GlcNAcylation as a key determinant of myofibroblastic activation and identifies its inhibition as an avenue to intervene with fibrogenic processes.

Carcass, Egg Characteristics and Leg Bone Dimensions of Pigeons of Different Origin.

In the past, studies have been conducted on the evaluation of meat traits of pigeons, but the knowledge obtained is incomplete and needs to be expanded. The purpose of this study was to obtain information on the weight and proportion of carcass elements, femur and tibia bone dimensions, and egg characteristics of meat of King breed and carrier pigeons. For this study, 16 carcasses of carrier pigeons and 16 carcasses of King pigeons were used, with 8 carcasses of males and 8 carcasses of females of each breed. Additionally, 20 eggs evaluated were from carrier pigeons and 20 eggs from King breed pigeons. The carcasses and eggs were obtained from birds that were 12 months old. The compared pigeon breeds differed (p < 0.05) significantly in terms of the weight of the eviscerated carcass with the neck; the content of neck, wings, pectoral and leg muscles in the carcass; as well as in terms of all specified dimensions of tibia and femur length and width. The origin of the pigeons had an effect (p < 0.05) on egg weight and dimensions, egg index, and the other studied egg traits, with the exception of eggshell weight and eggshell yellowness, yolk weight, yolk height, yolk diameter, and yolk index. So far, there have been no studies comparing carrier pigeons and King breed pigeons in terms of femur and tibia bone dimensions, morphological composition and egg dimensions, and egg content traits, which adds to the knowledge in this area and indicates the need for continuation in the future.

Natural compound screening predicts novel GSK-3 isoform-specific inhibitors.

Glycogen synthase kinase-3 (GSK-3) plays important roles in the pathogenesis of cardiovascular, metabolic, neurological disorders and cancer. Isoform-specific loss of either GSK-3α or GSK-3ß often provides cytoprotective effects under such clinical conditions. However, available synthetic small molecule inhibitors are relatively non-specific, and their chronic use may lead to adverse effects. Therefore, screening for natural compound inhibitors to identify the isoform-specific inhibitors may provide improved clinical utility. Here, we screened 70 natural compounds to identify novel natural GSK-3 inhibitors employing comprehensive in silico and biochemical approaches. Molecular docking and pharmacokinetics analysis identified two natural compounds Psoralidin and Rosmarinic acid as potential GSK-3 inhibitors. Specifically, Psoralidin and Rosmarinic acid exhibited the highest binding affinities for GSK-3α and GSK-3ß, respectively. Consistent with in silico findings, the kinase assay-driven IC50 revealed superior inhibitory effects of Psoralidin against GSK-3α (IC50 = 2.26 µM) vs. GSK-3ß (IC50 = 4.23 µM) while Rosmarinic acid was found to be more potent against GSK-3ß (IC50 = 2.24 µM) than GSK-3α (IC50 = 5.14 µM). Taken together, these studies show that the identified natural compounds may serve as GSK-3 inhibitors with Psoralidin serving as a better inhibitor for GSK-3α and Rosmarinic for GSK-3ß isoform, respectively. Further characterization employing in vitro and preclinical models will be required to test the utility of these compounds as GSK-3 inhibitors for cardiometabolic and neurological disorders and cancers.

GSK-3α-BNIP3 axis promotes mitophagy in human cardiomyocytes under hypoxia.

Dysregulated autophagy/mitophagy is one of the major causes of cardiac injury in ischemic conditions. Glycogen synthase kinase-3alpha (GSK-3α) has been shown to play a crucial role in the pathophysiology of cardiac diseases. However, the precise role of GSK-3α in cardiac mitophagy remains unknown. Herein, we investigated the role of GSK-3α in cardiac mitophagy by employing AC16 human cardiomyocytes under the condition of acute hypoxia. We observed that the gain-of-GSK-3α function profoundly induced mitophagy in the AC16 cardiomyocytes post-hypoxia. Moreover, GSK-3α overexpression led to increased ROS generation and mitochondrial dysfunction in cardiomyocytes, accompanied by enhanced mitophagy displayed by increased mt-mKeima intensity under hypoxia. Mechanistically, we identified that GSK-3α promotes mitophagy through upregulation of BNIP3, caused by GSK-3α-mediated increase in expression of HIF-1α and FOXO3a in cardiomyocytes post-hypoxia. Moreover, GSK-3α displayed a physical interaction with BNIP3 and, inhibited PINK1 and Parkin recruitment to mitochondria was observed specifically under hypoxia. Taken together, we identified a novel mechanism of mitophagy in human cardiomyocytes. GSK-3α promotes mitochondrial dysfunction and regulates FOXO3a -mediated BNIP3 overexpression in cardiomyocytes to facilitate mitophagy following hypoxia. An interaction between GSK-3α and BNIP3 suggests a role of GSK-3α in BNIP3 recruitment to the mitochondrial membrane where it enhances mitophagy in stressed cardiomyocytes independent of the PINK1/Parkin.

Effect of pentoxifylline on endothelial dysfunction, oxidative stress and inflammatory markers in STEMI patients.

Aim: ST-elevation myocardial infarction (STEMI) patients suffer higher mortality and adverse outcomes linked to endothelial dysfunction (ED). Methods: 43 patients were randomized to pentoxifylline (PTX) 400 mg thrice daily (n = 22) or placebo (n = 21). Soluble vascular cell adhesion molecule-1, malondialdehyde, interleukin-1 (IL-1), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α) were assessed at baseline and 2 months. Results: After 2 months, no significant difference was observed in markers' levels between the 2 groups. However, a within-group comparison revealed a statistically significant change in hs-CRP in the PTX group (10.057 (9.779-10.331) versus 9.721 (6.102-10.191)), p = 0.032. Conclusion: PTX for 2 months in STEMI patients was safe and well-tolerated but had no significant detectable effect on ED, oxidative stress or inflammatory markers. Clinical Trial Registration: NCT04367935 (ClinicalTrials.gov).

This study examined the effect and the safety of a drug called pentoxifylline in patients who have recently had a heart attack. Pentoxifylline can possibly reduce inflammation and is used for patients with blood flow issues. The study involved 43 participants, 22 receiving pentoxifylline and 21 receiving a placebo for 2 months. We measured different markers related to inflammation and heart health before and after. Overall, there was no significant difference between the groups, but patients who received pentoxifylline experienced less inflammation according to only one of the markers measured. This study concluded that the prescription of pentoxifylline after a heart attack is safe, well-tolerated and without notable side effects. Still, we recommend larger and longer studies to be sure of its effect.

Acinar to ß-like cell conversion through inhibition of focal adhesion kinase.

Insufficient functional ß-cell mass causes diabetes; however, an effective cell replacement therapy for curing diabetes is currently not available. Reprogramming of acinar cells toward functional insulin-producing cells would offer an abundant and autologous source of insulin-producing cells. Our lineage tracing studies along with transcriptomic characterization demonstrate that treatment of adult mice with a small molecule that specifically inhibits kinase activity of focal adhesion kinase results in trans-differentiation of a subset of peri-islet acinar cells into insulin producing ß-like cells. The acinar-derived insulin-producing cells infiltrate the pre-existing endocrine islets, partially restore ß-cell mass, and significantly improve glucose homeostasis in diabetic mice. These findings provide evidence that inhibition of the kinase activity of focal adhesion kinase can convert acinar cells into insulin-producing cells and could offer a promising strategy for treating diabetes.

Carcass characteristics, physicochemical traits, texture and microstructure of young and spent quails meat.

The purpose of the study was to compare young (6-wk-old) and spent (52-wk-old) Japanese quail in terms of body weight, carcass characteristics, and some meat quality traits. Whole carcasses were dissected, pectoral muscles and leg muscles were sampled for determination of basic chemical composition and L*a*b* color parameters, while m. pectoralis major was sampled for texture and microstructure traits. Age of quails had a significant effect on body weight, carcass weight, carcass yield, pectoral muscle, abdominal fat and skin with subcutaneous fat, and carcass remainders contents in eviscerated carcass. Spent quails had significantly higher intramuscular fat content in pectoral and leg muscles and protein content in breast muscle, and also lower content of water in breast and leg muscles than young quails. Slaughter age significantly affected lightness (L*) and redness (a*) of pectoral muscles, as well as texture traits (except for cohesiveness) and microstructure of m. pectoralis major, except for thickness of perimysium and endomysium. Regardless of age, quail sex had an effect on the carcass traits studied (except for leg muscle content), intramuscular fat content of pectoral and leg muscles, water content of leg muscles and yellowness of pectoral muscle. In addition, a significant effect of quail sex was found on cutting work, springiness, chewiness and marked microstructural characteristics, except for vertical fiber diameter. The interaction between age and sex was significant for most slaughter and microstructural characteristics and also WB-shear force of m. pectoralis major, and L*, b* pectoral muscles. Higher fatness of carcasses, higher intramuscular fat in meat, and poorer textural and microstructural characteristics of m. pectoralis major spent Japanese quail indicate poorer fulfillment of most consumers' requirements compared to carcasses and meat of young quails.

Unraveling the significance of PPP1R1A gene in pancreatic ß-cell function: A study in INS-1 cells and human pancreatic islets.

BACKGROUND AND AIMS: The protein phosphatase 1 regulatory inhibitor subunit 1A (PPP1R1A) has been linked with insulin secretion and diabetes mellitus. Yet, its full significance in pancreatic ß-cell function remains unclear. This study aims to elucidate the role of the PPP1R1A gene in ß-cell biology using human pancreatic islets and rat INS-1 (832/13) cells. RESULTS: Disruption of Ppp1r1a in INS-1 cells was associated with reduced insulin secretion and impaired glucose uptake; however, cell viability, ROS, apoptosis or proliferation were intact. A significant downregulation of crucial ß-cell function genes such as Ins1, Ins2, Pcsk1, Cpe, Pdx1, Mafa, Isl1, Glut2, Snap25, Vamp2, Syt5, Cacna1a, Cacna1d and Cacnb3, was observed upon Ppp1r1a disruption. Furthermore, silencing Pdx1 in INS-1 cells altered PPP1R1A expression, indicating that PPP1R1A is a target gene for PDX1. Treatment with rosiglitazone increased Ppp1r1a expression, while metformin and insulin showed no effect. RNA-seq analysis of human islets revealed high PPP1R1A expression, with α-cells showing the highest levels compared to other endocrine cells. Muscle tissues exhibited greater PPP1R1A expression than pancreatic islets, liver, or adipose tissues. Co-expression analysis revealed significant correlations between PPP1R1A and genes associated with insulin biosynthesis, exocytosis machinery, and intracellular calcium transport. Overexpression of PPP1R1A in human islets augmented insulin secretion and upregulated protein expression of Insulin, MAFA, PDX1, and GLUT1, while silencing of PPP1R1A reduced Insulin, MAFA, and GLUT1 protein levels. CONCLUSION: This study provides valuable insights into the role of PPP1R1A in regulating ß-cell function and glucose homeostasis. PPP1R1A presents a promising opportunity for future therapeutic interventions.

Secure Computing for Fog-Enabled Industrial IoT.

Smart cities are powered by several new technologies to enhance connectivity between devices and develop a network of connected objects which can lead to many smart industrial applications. This network known as the Industrial Internet of Things (IIoT) consists of sensor nodes that have limited computing capacity and are sometimes not able to execute intricate industrial tasks within their stipulated time frame. For faster execution, these tasks are offloaded to nearby fog nodes. Internet access and the diverse nature of network types make IIoT nodes vulnerable and are under serious malicious attacks. Malicious attacks can cause anomalies in the IIoT network by overloading complex tasks, which can compromise the fog processing capabilities. This results in an increased delay of task computation for trustworthy nodes. To improve the task execution capability of the fog computing node, it is important to avoid complex offloaded tasks due to malicious attacks. However, even after avoiding the malicious tasks, if the offloaded tasks are too complex for the fog node to execute, then the fog nodes may struggle to process all legitimate tasks within their stipulated time frame. To address these challenges, the Trust-based Efficient Execution of Offloaded IIoT Trusted tasks (EEOIT) is proposed for fog nodes. EEOIT proposes a mechanism to detect malicious nodes as well as manage the allocation of computing resources so that IIoT tasks can be completed in the specified time frame. Simulation results demonstrate that EEOIT outperforms other techniques in the literature in an IIoT setting with different task densities. Another significant feature of the proposed EEOIT technique is that it enhances the computation of trustable tasks in the network. The results show that EEOIT entertains more legitimate nodes in executing their offloaded tasks with more executed data, with reduced time and with increased mean trust values as compared to other schemes.

The Effects of Slaughter Age and Sex on Carcass Traits, Meat Quality, and Leg Bone Characteristics of Farmed Common Pheasants (Phasianus colchicus L.).

The aim of this study was to determine the effects of slaughter age and sex on the carcass characteristics, meat quality parameters, and leg bone dimensions of common pheasants. The study material consisted of 40 common pheasants, including 10 males and 10 females at 12 weeks of age and 10 males and 10 females at 15 weeks of age. The birds were kept on a farm in a semi-intensive system. The slaughter age had significant effects on the eviscerated carcass weight; the percentage of skin with subcutaneous fat; the wings percentage; electrical conductivity (EC24); the work required to cut the samples (cutting work); redness (a*); the intramuscular fat content in the breast meat; and the protein, intramuscular fat, water, and collagen contents in the leg meat. The sex of the pheasants had significant effects on the eviscerated carcass weight; the contents of leg muscles, skin with subcutaneous fat, and wings in the carcasses; and the electrical conductivity, thermal loss, lightness (L*), and redness (a*) of the breast muscles. It also significantly affected the protein and water contents of the pectoral and leg muscles, the intramuscular fat contents of the leg muscles, the texture traits of the pectoralis major muscle, and all femur and tibia bone dimensions. The results indicate a greater influence of sex compared to slaughter age on the pheasant traits studied. We confirmed the occurrence of a clearly marked sexual dimorphism in birds of this species. Both factors (slaughter age and gender) have significant effects on the nutritional and technological value of pheasant meat. The few studies on meat texture and the dimensions of pheasant leg bones indicate a need for continued research in this area in the future.

Encapsulation of Black Rice Bran Extract in a Stable Nanoemulsion: Effects of Thermal Treatment, Storage Conditions, and In Vitro Digestion.

This study aimed to improve the dispersibility of phenolic compounds from black rice bran through the encapsulation process within nanoemulsion. The study focused on assessing the stability of the nanoemulsions, which were prepared using a combination of surfactants with distinct hydrophilic-lipophilic balance (HLB) values and sunflower oil under different thermal treatments and storage conditions. The study revealed a significant correlation between the mixed surfactant HLB value and the nanoemulsions properties, including average particle size, polydispersity index (PDI), and ζ-potential. Specifically, an increase in the HLB value was associated with a decrease in the initial average particle size. The encapsulated polyphenols exhibited remarkable stability over a storage period of up to 30 days at different temperatures with no significant changes observed in particle size or PDI. The study also investigated the impact of different ionic strengths (0.2, 0.5, and 1.00 mol L-1 NaCl) on the physical stability and antioxidant black rice bran extract nanoemulsion, and the results revealed that adding NaCl influenced the particle size and surface charge of the nanoemulsions. Total phenolic content and DPPH results demonstrated a significant impact of salt concentration on antioxidant properties, with varying trends observed among the HLB formulations. Furthermore, the behavior of the encapsulated extracts during digestion was examined, and their antioxidant activity was evaluated.

Targeting inflammatory signaling pathways with SGLT2 inhibitors: Insights into cardiovascular health and cardiac cell improvement.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have attracted significant attention for their broader therapeutic impact beyond simply controlling blood sugar levels, particularly in their ability to influence inflammatory pathways. This review delves into the anti-inflammatory properties of SGLT2 inhibitors, with a specific focus on canagliflozin, empagliflozin, and dapagliflozin. One of the key mechanisms through which SGLT2 inhibitors exert their anti-inflammatory effects is by activating AMP-activated protein kinase (AMPK), a crucial regulator of both cellular energy balance and inflammation. Activation of AMPK by these inhibitors leads to the suppression of pro-inflammatory pathways and a decrease in inflammatory mediators. Notably, SGLT2 inhibitors have demonstrated the ability to inhibit the release of cytokines in an AMPK-dependent manner, underscoring their direct influence on inflammatory signaling. Beyond AMPK activation, SGLT2 inhibitors also modulate several other inflammatory pathways, including the NLRP3 inflammasome, expression of Toll-like receptor 4 (TLR-4), and activation of NF-κB (Nuclear factor kappa B). This multifaceted approach contributes to their efficacy in reducing inflammation and managing associated complications in conditions such as diabetes and cardiovascular disorders. Several human and animal studies provide support for the anti-inflammatory effects of SGLT2 inhibitors, demonstrating protective effects on various cardiac cells. Additionally, these inhibitors exhibit direct anti-inflammatory effects by modulating immune cells. Overall, SGLT2 inhibitors emerge as promising therapeutic agents for targeting inflammation in a range of pathological conditions. Further research, particularly focusing on the molecular-level pathways of inflammation, is necessary to fully understand their mechanisms of action and optimize their therapeutic potential in inflammatory diseases.

Sodium alginate films incorporated with Lepidium sativum (Garden cress) extract as a novel method to enhancement the oxidative stability of edible oil.

This study addresses the growing interest in bio-based active food packaging by infusing Lepidium sativum (Garden cress) seeds extract (GRCE) into sodium alginate (SALG) films at varying concentrations (1, 3, and 5 %). The GRCE extract revealed six phenolic compounds, with gallic and chlorogenic acids being prominent, showcasing substantial total phenolic content (TPC) of 139.36 µg GAE/mg and total flavonoid content (TFC) of 26.46 µg RE/mg. The integration into SALG films significantly increased TPC, reaching 30.73 mg GAE/g in the film with 5 % GRCE. This enhancement extended to DPPH and ABTS activities, with notable rises to 66.47 and 70.12 %, respectively. Physical properties, including tensile strength, thickness, solubility, and moisture content, were positively affected. A reduction in water vapor permeability (WVP) was reported in the film enriched with 5 % GRCE (1.389 × 10-10 g H2O/m s p.a.). FT-IR analysis revealed bands indicating GRCE's physical interaction with the SALG matrix, with thermal stability of the films decreasing upon GRCE integration. SALG/GRCE5 effectively lowered the peroxide value (PV) of sunflower oil after four weeks at 50 °C compared to the control, with direct film-oil contact enhancing this reduction. Similar trends were observed in the K232 and K270 values.

The potential impact and diagnostic value of inflammatory markers on diabetic foot progression in type II diabetes mellitus: A case-control study.

BACKGROUND: The wound-healing process in diabetic foot is affected by pro and anti-inflammatory markers, and any disruption in the inflammatory reaction interferes with tissue homeostasis, leading to chronic non-wound healing. AIM: This study aimed to determine the diagnostic value and effect of CRP, IL-6, TNF, and HbA1c on initiation the and progression of diabetic foot ulcers. METHOD: ELISA was used to quantify IL-6, TNF, CRP, and HbA1c in 205 patients with diabetes, and 105 were diabetic foot free. The prevalence and progression of diabetic foot were also evaluated. The area under the curve (AUC) was calculated using the receiver operating characteristic (ROC) curve to analyze the predictive values. Forward stepwise logistic regression analysis was used to compute the odds ratio (OR) and the corresponding 95% confidence intervals (CIs). RESULTS: CRP, IL-6, and FBS were found to be significant predictors of diabetic foot (OR=1.717, 95% CI=1.250-2.358, P=0.001; OR=1.434, 95% CI=1.142-1.802, P=0.002; and OR=1.040, 95% CI=1.002-1.080, P=0.037), respectively. The AUCs for CRP, IL-6, and HbA1c in predicting diabetic foot were 0.839, 0.728, and 0.834, respectively, demonstrating a good predictive value for each diagnostic marker. CONCLUSION: The current study demonstrated that IL-6, CRP, and HbA1c may be useful biomarkers to indicate diabetic foot progression. Furthermore, our findings showed a substantial relationship between CRP and HbA1c in individuals with diabetic foot conditions.

Asymmetric dual-core liquid crystal channel-based tunable mode converter.

In this work, a higher order-to-fundamental mode converter is reported and analyzed based on an asymmetric dual channel waveguide (ADC-WG) on silicon. In the reported structure, one of the two waveguides is infiltrated with nematic liquid crystal (NLC) material to add temperature tunability while the other one is a solid BK7 waveguide. The modal characteristics are obtained using the full vectorial finite difference method (FVFDM). In addition, the structural parameters and optical characteristics of the employed materials are investigated to achieve good wavelength selectivity with a short device length (LD). Thus, a compact mode converter that can work at different wavelengths including the telecommunication wavelength i.e., 1.55 µm with LD ~ 482.31 µm and a low crosstalk of - 19.86 dB is presented. To prove the thermal tunability of the suggested mode converter, its operation is tested through a temperature range between 20 and 35 °C and the results show that the mode conversion process is achieved at each temperature with different phase matching wavelengths (λPMW) but with quite similar coupling length (LC). The proposed device can therefore be effectively utilized in integrated photonic circuits.

Chitosan/alginate/pectin biopolymer-based Nanoemulsions for improving the shelf life of refrigerated chicken breast.

This study investigated the use of nanoemulsions and various polymer coatings to enhance the quality and shelf life of chicken breast. This comprehensive study explored the antibacterial activity of essential oils (EOs) against Escherichia coli and Staphylococcus aureus, as well as the characterization of nanoemulsions (Nes) and nanoemulsion-based coatings. The antimicrobial potential of EOs, such as cinnamon, tea tree, jojoba, thyme, and black cumin seed oil, was evaluated against microorganisms, and thyme oil exhibited the highest inhibitory effect, followed by cinnamon and tea tree oil by disk diffusion analysis. The MIC and MBC values of EOs were found between 0.16-2.5 mg/mL and 0.16-5 mg/mL, respectively, while thyme EO resulted in the lowest values showing its antimicrobial potential. Then, the essential oil nanoemulsions (EONe) and their coatings, formulated with thyme oil, alginate, chitosan, and pectin, were successfully characterized. Optical microscope observations confirmed the uniform distribution of droplets in all (EONe), while particle size analysis demonstrated multimodal droplet size distributions. The EONe-chitosan coating showed the highest efficacy in reducing cooking loss, while the EONe-chitosan, EONe-alginate, and EONe-pectin coatings displayed promising outcomes in preserving color stability. Microbial analysis revealed the significant inhibitory effects of the EONe-chitosan coating against mesophilic bacteria, psychrophilic bacteria, and yeasts, leading to an extended shelf life of chicken breast. These results suggest the potential application of thyme oil and NE-based coatings in various industries for antimicrobial activity and quality preservation.

Endoscopic Thyroidectomy for Large-Sized Goiters: Merits of the Axillo-Breast Approach with Gas Insufflation.

Background: Several minimal access approaches to the thyroid gland have been widely applied; nevertheless, such approaches are still challenging when dealing with large-sized thyroid nodules or goiters. We hereby evaluated the outcomes and highlighted the merits of endoscopic axillo-breast hemithyroidectomy (EABH) for large-sized unilateral goiters. Methods: Patients underwent EABH for unilateral large thyroid nodules ≥6 cm in its greatest dimension or unilateral large goiter (≥60 ml sonographic volume) whatever the size of its contained nodules were identified from a prospectively maintained database. Their demographic data, clinicopathological profiles, and surgical and esthetic outcomes are reported and analyzed. Results: Over a 2-year period, 33 patients matched the selection criteria. Their mean age was 34.75 ± 11.39 years. There were 30 women and 3 men. The majority of nodules were radiologically TIRADS3 and cytologically Bethesda 3. The mean sonographic dominant nodule greatest dimension was 5.29 ± 1.48 cm (range: 3-9.5 cm). The mean sonographic volume of the pathological lobe was 101.86 ± 54.45 ml (range: 60.11-236.88 ml). All cases were completed endoscopically with no conversion to open. The mean operative time was 110.76 ± 18.75 minutes. No significant postoperative complications were reported except for one case with temporary vocal cord paresis. Most (87.9%) of the patients were extremely satisfied with the procedure. Conclusion: EABH with our suggested key steps could be considered an effective valid approach for unilateral large goiters in trained hands and in patients desirous for cosmesis.

Targeting Hypoxia-Inducible Factor-1 (HIF-1) in Cancer: Emerging Therapeutic Strategies and Pathway Regulation.

Hypoxia-inducible factor-1 (HIF-1) is a key regulator for balancing oxygen in the cells. It is a transcription factor that regulates the expression of target genes involved in oxygen homeostasis in response to hypoxia. Recently, research has demonstrated the multiple roles of HIF-1 in the pathophysiology of various diseases, including cancer. It is a crucial mediator of the hypoxic response and regulator of oxygen metabolism, thus contributing to tumor development and progression. Studies showed that the expression of the HIF-1α subunit is significantly upregulated in cancer cells and promotes tumor survival by multiple mechanisms. In addition, HIF-1 has potential contributing roles in cancer progression, including cell division, survival, proliferation, angiogenesis, and metastasis. Moreover, HIF-1 has a role in regulating cellular metabolic pathways, particularly the anaerobic metabolism of glucose. Given its significant and potential roles in cancer development and progression, it has been an intriguing therapeutic target for cancer research. Several compounds targeting HIF-1-associated processes are now being used to treat different types of cancer. This review outlines emerging therapeutic strategies that target HIF-1 as well as the relevance and regulation of the HIF-1 pathways in cancer. Moreover, it addresses the employment of nanotechnology in developing these promising strategies.

Discovery of Novel Pyridazine-Tethered Sulfonamides as Carbonic Anhydrase II Inhibitors for the Management of Glaucoma.

As a progressive neuropathic condition, glaucoma can cause lifelong blindness if left untreated. Novel phenylpyridazine-tethered sulfonamides were designed as selective inhibitors for carbonic anhydrase (CA) isoform II to find effective therapeutic agents for glaucoma. Subsequently, the target inhibitors were synthesized and assessed for their inhibitory action against cytosolic CA I and II. Interestingly, the synthesized molecules poorly inhibited CA I while exhibiting low subnanomolar potency against CA II. Compound 7c disclosed the most potent activity (IC50 = 0.63 nM) with high selectivity against CA II (605-fold than acetazolamide selectivity). Moreover, compound 7c also showed significant in vivo IOP-reducing properties in the in vivo model of glaucoma. Furthermore, the binding of compound 7c to CA II was assessed at the molecular level, exploiting the molecular docking approach.

Salmonellosis: An Overview of Epidemiology, Pathogenesis, and Innovative Approaches to Mitigate the Antimicrobial Resistant Infections.

Salmonella is a major foodborne pathogen and a leading cause of gastroenteritis in humans and animals. Salmonella is highly pathogenic and encompasses more than 2600 characterized serovars. The transmission of Salmonella to humans occurs through the farm-to-fork continuum and is commonly linked to the consumption of animal-derived food products. Among these sources, poultry and poultry products are primary contributors, followed by beef, pork, fish, and non-animal-derived food such as fruits and vegetables. While antibiotics constitute the primary treatment for salmonellosis, the emergence of antibiotic resistance and the rise of multidrug-resistant (MDR) Salmonella strains have highlighted the urgency of developing antibiotic alternatives. Effective infection management necessitates a comprehensive understanding of the pathogen's epidemiology and transmission dynamics. Therefore, this comprehensive review focuses on the epidemiology, sources of infection, risk factors, transmission dynamics, and the host range of Salmonella serotypes. This review also investigates the disease characteristics observed in both humans and animals, antibiotic resistance, pathogenesis, and potential strategies for treatment and control of salmonellosis, emphasizing the most recent antibiotic-alternative approaches for infection control.