mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process.

The mammalian target of rapamycin (mTOR) is a pivotal regulator, integrating diverse environmental signals to control fundamental cellular functions, such as protein synthesis, cell growth, survival, and apoptosis. Embedded in a complex network of signaling pathways, mTOR dysregulation is implicated in the onset and progression of a range of human diseases, including metabolic disorders such as diabetes and cardiovascular diseases, as well as various cancers. mTOR also has a notable role in aging. Given its extensive biological impact, mTOR signaling is a prime therapeutic target for addressing these complex conditions. The development of mTOR inhibitors has proven advantageous in numerous research domains. This review delves into the significance of mTOR signaling, highlighting the critical components of this intricate network that contribute to disease. Additionally, it addresses the latest findings on mTOR inhibitors and their clinical implications. The review also emphasizes the importance of developing more effective next-generation mTOR inhibitors with dual functions to efficiently target the mTOR pathways. A comprehensive understanding of mTOR signaling will enable the development of effective therapeutic strategies for managing diseases associated with mTOR dysregulation.

Inhibition of pyruvate dehydrogenase accelerates anaerobic glycolysis under postmortem simulating conditions.

This research aimed to explore the potential influence of mitochondria on the rate of anaerobic glycolysis. We hypothesized that mitochondria could reduce the rate of anaerobic glycolysis and pH decline by metabolizing a portion of glycolytic pyruvate. We utilized an in vitro model and incorporated CPI-613 and Avidin to inhibit pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC), respectively. Four treatments were tested: 400 µM CPI-613, 1.5 U/ml Avidin, 400 µM CPI-613 + 1.5 U/ml Avidin, or control. Glycolytic metabolites and pH of the in vitro model were evaluated throughout a 1440-min incubation period. CPI-613-containing treatments, with or without Avidin, decreased pH levels and increased glycogen degradation and lactate accumulation compared to the control and Avidin treatments (P < 0.05), indicating increased glycolytic flux. In a different experiment, two treatments, 400 µM CPI-613 or control, were employed to track the fates of pyruvate using [13C6]glucose. CPI-613 reduced the contribution of glucose carbon to tricarboxylic acid cycle intermediates compared to control (P < 0.05). To test whether the acceleration of acidification in reactions containing CPI-613 was due to an increase in the activity of key enzymes of glycogenolysis and glycolysis, we evaluated the activities of glycogen phosphorylase, phosphofructokinase, and pyruvate kinase in the presence or absence of 400 µM CPI-613. The CPI-613 treatment did not elicit an alteration in the activity of these three enzymes. These findings indicate that inhibiting PDH increases the rate of anaerobic glycolysis and pH decline, suggesting that mitochondria are potential regulators of postmortem metabolism.

Influence of lip position on esthetics perception with respect to profile divergence using silhouette images.

BACKGROUND: The aim of the study was to determine the facial divergence and lip position combinations that are most and least preferred, and to investigate whether age or gender has an impact on these preferences. METHODS: The current investigation was carried out on a sample of 1077 individuals who were not experts in the field (253 men and 824 females). The research employed black silhouette photographs of profiles featuring different lip locations and profile divergences. The recruitment of participants was conducted in order to assess the attractiveness of the profiles, employing a Likert scale. The various positions of the lips and variations in facial profiles were thoroughly categorized. Results were analyzed using the Chi-square test. RESULTS: The findings of the research demonstrated that aesthetic perceptions displayed diversity when considering different lip locations and profile divergences. It was shown that neutral lip positions were predominantly favored, accounting for approximately 40.2% of the total frequencies in the anterior diverging group. It is noteworthy to highlight the aesthetically pleasing features exhibited by those with the most prominent lip position, occurring at a frequency of 10.9% in straight-diverging group. In the posterior divergent group, the most protruded lip position, showed very attractive aesthetics with frequency (7.1%). Gender, age, region, and level of education had significant influence on aesthetic perception. CONCLUSIONS: The variety of aesthetic preferences is influenced by the location of the lips and the divergence of the facial profile, resulting in different outcomes within the categories of anterior, straight, and posterior divergence. Clinicians are advised to customize the treatment regimen in order to correspond with the unique desires and preferences of the patient.

An Overview of the Role of Furin in Type 2 Diabetes.

Post-translational modifications (PTMs) play important roles in regulating several human diseases, like cancer, neurodegenerative disorders, and metabolic disorders. Investigating PTMs' contribution to protein functions is critical for modern biology and medicine. Proprotein convertases (PCs) are irreversible post-translational modifiers that have been extensively studied and are considered as key targets for novel therapeutics. They cleave proteins at specific sites causing conformational changes affecting their functions. Furin is considered as a PC model in regulating growth factors and is involved in regulating many pro-proteins. The mammalian target of the rapamycin (mTOR) signaling pathway is another key player in regulating cellular processes and its dysregulation is linked to several diseases including type 2 diabetes (T2D). The role of furin in the context of diabetes has been rarely explored and is currently lacking. Moreover, furin variants have altered activity that could have implications on overall health. In this review, we aim to highlight the role of furin in T2D in relation to mTOR signaling. We will also address furin genetic variants and their potential effect on T2D and ß-cell functions. Understanding the role of furin in prediabetes and dissecting it from other confounding factors like obesity is crucial for future therapeutic interventions in metabolic disorders.

Targeting SARS-CoV-2 Macrodomain-1 to Restore the Innate Immune Response Using In Silico Screening of Medicinal Compounds and Free Energy Calculation Approaches.

Among the different drug targets of SARS-CoV-2, a multi-domain protein known as NSP3 is a critical element of the translational and replication machinery. The macrodomain-I, in particular, has been reported to have an essential role in the viral attack on the innate immune response. In this study, we explore natural medicinal compounds and identify potential inhibitors to target the SARS-CoV-2-NSP3 macrodomain-I. Computational modeling and simulation tools were utilized to investigate the structural-dynamic properties using triplicates of 100 ns MD simulations. In addition, the MM/GBSA method was used to calculate the total binding free energy of each inhibitor bound to macrodomain-I. Two significant hits were identified: 3,5,7,4'-tetrahydroxyflavanone 3'-(4-hydroxybenzoic acid) and 2-hydroxy-3-O-beta-glucopyranosyl-benzoic acid. The structural-dynamic investigation of both compounds with macrodomain-I revealed stable dynamics and compact behavior. In addition, the total binding free energy for each complex demonstrated a robust binding affinity, of ΔG -61.98 ± 0.9 kcal/mol for Compound A, while for Compound B, the ΔG was -45.125 ± 2.8 kcal/mol, indicating the inhibitory potential of these compounds. In silico bioactivity and dissociation constant (KD) determination for both complexes further validated the inhibitory potency of each compound. In conclusion, the aforementioned natural products have the potential to inhibit NSP3, to directly rescue the host immune response. The current study provides the basis for novel drug development against SARS-CoV-2 and its variants.

Exploring the Binding Mechanism of NRG1-ERBB3 Complex and Discovery of Potent Natural Products to Reduce Diabetes-Assisted Breast Cancer Progression.

Diabetes mellitus significantly contributes to breast cancer progression, where hyperglycemia upregulates specific genes, leading to more aggressive tumor growth. In patients with BC that develop diabetes, neuregulin 1 (NRG1) and epidermal growth factor receptor 3 (ERBB3) overexpression exacerbate tumor growth and progression. Since the interaction between NRG1 and ERBB3 is critical for tumor growth, understanding the molecular mechanisms underlying NRG1-ERBB3 complex formation is essential for elucidating diabetes-assisted breast cancer progression. However, the key residues forming the NRG1-ERBB3 complex remain unknown. Here, we substituted specific residues in NRG1 with alanine and studied its interactions with ERBB3 using computational structural biology tools. We further screened the South African natural compounds database to target the complex's interface residues to discover potential inhibitors. The conformational stability and dynamic features of NRG1-WT, -H2A, -L3A, and -K35A complexed with ERBB3 were subjected to 400 ns molecular dynamics simulations. The free binding energies of all NRG1-ERBB3 complexes were calculated using the molecular mechanics-generalized Born surface area (MM/GBSA). The H2 and L3 alanine substitutions caused a loss of interaction with ERBB3 residue D73, weakening the interaction with ERBB3. Screening 1300 natural compounds identified four (SANC00643, SANC00824, SANC00975, and SANC00335) with the best potential to inhibit ERRB3-NRG1 coupling. The binding free energies for each complex were - 48.55 kcal/mol for SANC00643, - 47.68 kcal/mol for SANC00824, - 46.04 kcal/mol for SANC00975, and - 45.29 kcal/mol for SANC00335, showing their overall stronger binding with ERBB3 than NRG1 and their potential to act as ERBB3-NRG1 complex inhibitors. In conclusion, this complex may represent a residue-specific drug target to inhibit BC progression.

Perceived responsibility for mechanical ventilation and weaning decisions in intensive care units in the Kingdom of Saudi Arabia.

Background: Optimizing patient outcomes and reducing complications require constant monitoring and effective collaboration among critical care professionals. The aim of the present study was to describe the perceptions of physician directors, respiratory therapist managers and nurse managers regarding the key roles, responsibilities and clinical decision-making related to mechanical ventilation and weaning in adult Intensive Care Units (ICUs) in the Kingdom of Saudi Arabia (KSA). Methods: A multi-centre, cross-sectional self-administered survey was sent to physician directors, respiratory therapist managers and nurse managers of 39 adult ICUs at governmental tertiary referral hospitals in 13 administrative regions of the KSA. The participants were advised to discuss the survey with the frontline bedside staff to gather feedback from the physicians, respiratory therapists and nurses themselves on key mechanical ventilation and weaning decisions in their units. We performed T-test and non-parametric Mann-Whitney U tests to test the physicians, respiratory therapists, and nurses' autonomy and influence scores, collaborative or single decisions among the professionals. Moreover, logistic regressions were performed to examine organizational variables associated with collaborative decision-making. Results: The response rate was 67% (14/21) from physician directors, 84% (22/26) from respiratory therapist managers and 37% (11/30) from nurse managers. Physician directors and respiratory therapist managers agreed to collaborate significantly in most of the key decisions with limited nurses' involvement (P<0.01). We also found that physician directors were perceived to have greater autonomy and influence in ventilation and waning decision-making with a mean of 8.29 (SD±1.49), and 8.50 (SD±1.40), respectively. Conclusion: The key decision-making was implemented mainly by physicians and respiratory therapists in collaboration. Nurses had limited involvement. Physician directors perceived higher autonomy and influence in ventilatory and weaning decision-making than respiratory therapist managers and nurse managers. A critical care unit's capacity to deliver effective and safe patient care may be improved by increasing nurses' participation and acknowledging the role of respiratory therapists in clinical decision-making regarding mechanical ventilation and weaning.

A positive correlation between daily spiritual practice and reduced depressive symptoms among older adults: evidence from a nationally representative survey among the Indian population.

BACKGROUND: This study explored the factors associated with daily spiritual experiences of older adults and the association of daily spiritual experiences with major depressive disorder among older Indian adults. METHODS: Data for this study were derived from the Longitudinal Ageing Study in India (LASI) wave-1. The sample size was 31 464 older adults age 60 years and above. Daily spiritual experience was assessed from four items (Cronbach's alpha: 0.89) adapted from the daily spiritual experience scale (DSES). Major depressive disorder was calculated using the Short Form Composite International Diagnostic Interview (CIDI-SF). Descriptive, bivariate and multivariable forward stepwise logistic regression analyses were conducted to fulfil the objectives of the study. RESULTS: A proportion of 87.46% of older adults reported daily spiritual experiences in the study. Women had higher odds of spiritual experiences than men (adjusted odds ratio (aOR): 1.243; confidence interval (CI): 1.041-1.484). Older adults with higher education, those who were retired, those who reported community involvement or were physically active or belonged to the richest wealth quintile had higher odds of having daily spiritual experiences in comparison to older adults from the poorest wealth quintile. Further, older adults with daily spiritual experiences had significantly lower odds of major depressive disorder (aOR: 0.810; CI: 0.681-0.964) than older adults who did not report daily spiritual experiences. CONCLUSION: The study suggests that daily spiritual practices can be a strategy to reduce major depressive symptoms and improve mental health and wellbeing of older adults, and future studies are warranted on this direction.

Commiphora myrrha stimulates insulin secretion from ß-cells through activation of atypical protein kinase C and mitogen-activated protein kinase.

ETHNOPHARMACOLOGICAL RELEVANCE: Ayurvedic medicine has been used in the treatment of diabetes mellitus for centuries. In Arabia and some areas of Africa, Commiphora myrrha (CM) has been extensively used as a plant-based remedy. We have previously shown that an aqueous CM resin solution directly stimulates insulin secretion from MIN6 cells, a mouse ß-cell line, and isolated mouse and human islets. However, the signaling pathways involved in CM-induced insulin secretion are completely unknown. Insulin secretion is normally triggered by elevations in intracellular Ca2+ ([Ca2+]i) through voltage gated Ca2+ channels (VGCC) and activation of protein kinases. Protein and lipid kinases such as protein kinase A (PKA), Ca2+-calmodulin dependent protein kinase II (CaMKII), phosphoinositide 3-kinases (PI3Ks), protein kinase C (PKC) and mitogen-activated protein kinase (MAPK), specifically extracellular signal-regulated kinases (ERK1/2), may be involved in receptor-operated insulin secretion. Therefore, we hypothesized that CM may induce insulin secretion by modulating the activity of VGCC and/or one or more of the above kinases. AIM OF THE STUDY: To investigate the possible molecular mechanism of action of CM-induced insulin secretion. The effects of aqueous CM resin extract on [Ca2+]i and protein kinase activation from ß-cells were examined. METHODS: The effect of aqueous CM resin solution on [Ca2+]i was assessed using Ca2+ microfluorimetry. The involvement of VGCC in CM-induced insulin secretion was investigated using static and perifusion insulin secretion experiments in the presence of either EGTA, a Ca2+ chelator, or nifedipine, a blocker of VGCC. The involvement of kinase activation in the stimulatory effect of CM on insulin secretion was examined by using static and perifusion insulin secretion experiments in the presence of known pharmacological inhibitors and/or downregulation of specific kinases. The effects of CM on phosphorylation of PKCζ and ERK1/2 were also assessed using the Wes™ capillary-based protein electrophoresis. RESULTS: Ca2+ microfluorimetry measurements showed that exposing MIN6 cells to CM (0.5-2 mg/mL) was not associated with changes in [Ca2+]i. Similarly, incubating MIN6 cells and mouse islets with EGTA and nifedipine, respectively, did not attenuate the insulin secretion induced by CM. However, incubating mouse and human islets with CM in the presence of staurosporine, a non-selective protein kinase inhibitor, completely blocked the effect of CM on insulin secretion. Exposing mouse islets to CM in the presence of H89, KN62 and LY294002, inhibitors of PKA, CaMKII and PI3K, respectively, did not reduce CM-induced insulin secretion. However, incubating mouse and human islets with CM in the presence of Ro 31-8220, a pan-PKC inhibitor, diminished insulin secretion stimulated by CM, whereas inhibiting the action of typical PKC (with Go6976) and PLCß (with U73122) did not affect CM-stimulated insulin secretion. Similarly, downregulating typical and novel PKC by chronic exposure of mouse islets to phorbol 12-myristate 13-acetate (PMA) was also not associated with a decrease in the stimulatory effect of CM on insulin secretion. Interestingly, CM-induced insulin secretion from mouse islets was inhibited in the presence of the PKCζ inhibitor ZIP and a MAPK inhibitor PD 98059. In addition, Wes™ capillary-based protein electrophoresis indicated that expression of the phosphorylated forms of PKCζ and ERK1/2, a MAPK, was significantly increased following exposure of INS-1832/13 cells, a rat insulinoma cell line, to CM. CONCLUSIONS: Our data indicate that CM directly stimulates insulin secretion through activating known downstream effectors of insulin-stimulus secretion coupling. Indeed, the increase in insulin secretion seen with CM is independent of changes in [Ca2+]i and does not involve activation of VGCC. Instead, the CM stimulatory effect on insulin secretion is completely dependent on protein kinase activation. Our findings indicate that CM could induce insulin exocytosis by stimulating the phosphorylation and activation of PKCζ, which in turn phosphorylates and activates ERK1/2.

Discovery of natural products to block SARS-CoV-2 S-protein interaction with Neuropilin-1 receptor: A molecular dynamics simulation approach.

Neuropilin-1 (NRP1) is a widely expressed cell surface receptor protein characterized by its pleiotropic function. Recent reports highlighted NRP1 as an additional entry point of the SARS-CoV-2 virus, enhancing viral infectivity by interacting with the S-protein of SARS-CoV-2. The ubiquitous distribution and mechanism of action of NRP1 enable the SARS-CoV-2 virus to attack multiple organs in the body simultaneously. Therefore, blocking NRP1 is a potential therapeutic approach against SARS-CoV-2 infection. The current study screened the South African natural compounds database (SANCDB) for molecules that can disrupt the SARS-CoV-2 S protein-NRP1 interaction as a potential antiviral target for SARS-CoV-2 cellular entry. Following excessive screening and validation analysis 3-O-Methylquercetin and Esculetin were identified as potential compounds to disrupt the S-protein-NRP1 interaction. Furthermore, to understand the conformational stability and dynamic features between NRP1 interaction with the selected natural products, we performed 200 ns molecular dynamics (MD) simulations. In addition, molecular mechanics-generalized Born surface area (MM/GBSA) was utilized to calculate the free binding energies of the natural products interacting with NRP1. 3-O-methylquercetin showed an inhibitory effect with binding energies ΔG of -25.52 ±â€¯0.04 kcal/mol to NRP1, indicating the possible disruption of the NRP1-S-protein interaction. Our analysis demonstrated that 3-O-methylquercetin presents a potential antiviral compound against SARS-CoV-2 infectivity. These results set the path for future functional in-vitro and in-vivo studies in SARS-CoV-2 research.

Prevalence of Dry Eye Disease and Its Association With the Frequent Usage of Eye Cosmetics Among Women.

PURPOSE: Dry eye disease (DED) is defined as a disease of the tear film and ocular surface that leads to discomfort and visual disturbance. The diagnosis of DED mainly depends on the presenting clinical features. A delay in treatment may progress into chronic eye disease. This study aimed to estimate the prevalence of dry eye symptoms among eye cosmetic users in the Kingdom of Saudi Arabia. METHODS: This cross-sectional study involved adult Saudi females using eye cosmetics. The Ocular Surface Disease Index questionnaire was used to assess DED. RESULTS: A total of 207 responses were included in this study. DED symptoms were reported among those who used eye cosmetics suggesting their effect on the tear film and its stability. This study demonstrated that mascara is the most common cosmetic used, with a prevalence of 98.6%. The prevalence of dry eye syndrome (DES) was 71.6%, where 40.5%, 13.5%, and 17.6% had severe, moderate, and mild conditions, respectively. The frequency of using inner eyeliner significantly increased the prevalence of DES, in which those who used it daily accounted for 75%. In contrast, the results showed no correlation between the frequency of using mascara or external eyeliner and the prevalence of DES. CONCLUSION: The prevalence of DED among women who used eye cosmetics was much higher than its prevalence in the general population, which indicates that eye cosmetics are one of the risk factors in the development of DED. Also, the severity of DED was significantly higher in women who did not use a cleanser for removing cosmetics.

Spectro 1-A Potential Spectrophotometer for Measuring Color and Myoglobin Forms in Beef.

The objective of this study was to compare the Color Muse Spectro 1 sensor to the HunterLab MiniScan XE Plus spectrophotometer for evaluating beef color. Color coordinates (lightness (L*), redness (a*), yellowness (b*), chroma (C*), and hue (h*)), myoglobin redox forms (metmyoglobin (MMb), deoxymyoglobin (DMb), and oxymyoglobin (OMb)), and metmyoglobin reducing ability (MRA) were measured on beef steaks over a 5-days storage period. The results indicated that L*, b*, C*, MMb%, OMb%, and MRA% values obtained with Spectro 1 were comparable to those of MiniScan. However, Spectro 1 values for a* were overestimated compared to MiniScan (p < 0.05), whereas those for h* and DMb% were underestimated (p < 0.05). Regardless, Spectro 1 had the capability to detect changes in color coordinates, myoglobin forms, and MRA throughout the storage period. Bland−Altman plots demonstrated that L*, b*, and C* are interchangeable between the two instruments, but it was not the case for a*, h*, myoglobin forms, and MRA. Color coordinates measured by Spectro 1 exhibited excellent stability over time, evidenced by the low total color difference (ΔE*ab) values. Collectively, these findings indicate that Spectro 1 is a potential alternative spectrophotometer for studying meat color and myoglobin redox forms.

Cattle breed type and anabolic implants impact calpastatin expression and abundance of mRNA associated with protein turnover in the longissimus thoracis of feedlot steers.

Two methods that the beef cattle industry can use to improve efficiency, sustainability, and economic viability are growth promotants and crossbreeding cattle of different breed types. In the United States, over 90% of cattle receive an anabolic implant at some point during production resulting in an overall increase in skeletal muscle growth. Recent research suggests that the two main cattle breed types, Bos indicus and Bos taurus, respond differently to anabolic implants. The objective of this study was to characterize changes that occur in skeletal muscle following implanting in Bos indicus influenced steers or Bos taurus steers. Twenty steers were stratified by initial weight in a 2 × 2 factorial design examining two different breeds: Angus (AN; n = 10) or Santa Gertrudis influenced (SG; n = 10), and two implant strategies: no implant (CON; n = 10) or a combined implant containing 120 mg TBA and 24 mg E2 (IMP; n = 10; Revalor-S, Merck Animal Health). Skeletal muscle biopsies were taken from the longissimus thoracis (LT) 2 and 10 d post-implantation. The mRNA abundance of 24 genes associated with skeletal muscle growth were examined, as well as the protein expression of µ-calpain and calpastatin. Succinate dehydrogenase mRNA abundance was impacted (P = 0.05) by a breed × treatment interaction 2 d post-implanting, with SG-CON having a greater increased abundance than all other steers. A tendency for a breed × treatment interaction was observed for calpain-6 mRNA (P = 0.07), with SG-CON having greater abundance than AN-CON and SG-IMP. Additionally, calpastatin protein expression was altered (P = 0.01) by a breed × treatment interaction, with SG-CON and SG-IMP steers having increased expression (P = 0.01) compared with AN-CON steers. At 2 d post-implanting, a breed × treatment interaction was observed with SG-CON steers having greater (P = 0.05) mRNA abundance of mitogen-activated protein kinase compared with AN-CON steers. Furthermore, breed affected (P = 0.05) calpastatin abundance with AN steers having increased (P = 0.05) abundance 2 d post-implanting compared with SG steers. Meanwhile, implants tended to affect (P = 0.09) muscle RING finger protein-1 mRNA abundance, with CON steers having increased (P = 0.09) abundance compared with that of IMP steers. These findings suggest that cattle breed type and anabolic implants impact calpastatin expression and mRNA abundance associated with protein turnover in the LT of feedlot steers 2 and 10 d post-implantation.

Two methods that the beef cattle industry can use to potentially improve efficiency, sustainability, and economic viability are growth promotants and crossbreeding cattle of different breed types. In the United States, over 90% of cattle receive at least one anabolic implant during the production cycle resulting in improvements in production and overall economic and environmental sustainability. Research suggests that the two main cattle breed types, Bos indicus and Bos taurus, respond differently to different anabolic implant strategies. The objective of this study was to characterize changes that occur in the skeletal muscle following implanting in Bos indicus influenced animals and Bos taurus animals. This research measured mRNA abundance of 24 genes associated with skeletal muscle growth, and protein expression of calpain-1 and calpastatin. The findings of this research suggest that anabolic implants and cattle breed type interact to cause changes in mRNA abundance in the longissimus thoracis that are related to protein turnover of skeletal muscle. Furthermore, calpastatin protein abundance was also altered by this breed × treatment interaction. This research demonstrates that anabolic implants cause molecular changes in skeletal muscle of feedlot steers, with some of these changes being breed dependent.

Tandem mass tag labeling to assess proteome differences between intermediate and very tender beef steaks.

Tenderness is considered as one of the most important quality attributes dictating consumers' overall satisfaction and future purchasing decisions of fresh beef. However, the ability to predict and manage tenderness has proven very challenging due to the numerous factors that contribute to variation in end-product tenderness. Proteomic profiling allows for global examination of differentially abundant proteins in the meat and can provide new insight into biological mechanisms related to meat tenderness. Hence, the objective of this study was to examine proteomic profiles of beef longissimus lumborum (LL) steaks varying in tenderness, with the intention to identify potential biomarkers related to tenderness. For this purpose, beef LL muscle samples were collected from 99 carcasses at 0 and 384 h postmortem. Based on Warner-Bratzler shear force values at 384 h, 16 samples with the highest (intermediate tender, IT) and lowest (very tender, VT) values were selected to be used for proteomic analysis in this study (n = 8 per category). Using tandem mass tag-based proteomics, a total of 876 proteins were identified, of which 51 proteins were differentially abundant (P < 0.05) between the tenderness categories and aging periods. The differentially identified proteins encompassed a wide array of biological processes related to muscle contraction, calcium signaling, metabolism, extracellular matrix organization, chaperone, and apoptosis. A greater (P < 0.05) relative abundance of proteins associated with carbohydrate metabolism and apoptosis, and a lower (P < 0.05) relative abundance of proteins involved in muscle contraction was observed in the VT steaks after aging compared with the IT steaks, suggesting that more proteolysis occurred in the VT steaks. This may be explained by the greater (P < 0.05) abundance of chaperonin and calcium-binding proteins in the IT steaks, which could have limited the extent of postmortem proteolysis in these steaks. In addition, a greater (P < 0.05) abundance of connective tissue proteins was also observed in the IT steaks, which likely contributed to the difference in tenderness due to added background toughness. The established proteomic database obtained in this study may provide a reference for future research regarding potential protein biomarkers that are associated with meat tenderness.

Among all the eating quality attributes of beef, tenderness is considered an essential factor influencing consumers' overall satisfaction and future purchasing decisions. However, managing and predicting tenderness of meat products is challenging for the meat industry, as many factors can influence this attribute. The goal of this research was to examine variations in protein abundance between two categories of beef strip steaks varying in tenderness, with the intention to identify proteins related to beef tenderness/toughness. Overall, the results from this study suggest that tender steaks experienced greater protein degradation during aging than tougher steaks, which likely contributed to their improved tenderness. Furthermore, a greater abundance of connective tissue proteins, which are associated with meat toughness, was observed in the tougher steaks. Our results collectively indicate that the difference in tenderness between the two groups of steaks may be due to multiple proteins involved in several biological processes.

Liver and Gastrointestinal Involvement in Patients With COVID-19: A Retrospective Study.

Background Coronavirus disease 2019 (COVID-19) classically presents as a respiratory illness with fever, dry cough, and dyspnea on exertion. Along with respiratory signs and symptoms, gastrointestinal (GI) manifestations and liver injury have been recognized during the progression of the disease. This study aimed to determine the prevalence of GI symptoms and hepatic injury during COVID-19 infections and their consequences on the outcome of the disease. Methodology We conducted a retrospective survey of 715 participants age 16 or older diagnosed with COVID-19 and reported GI and hepatic manifestations in the Dammam Medical Complex in Dammam, Eastern Province, Saudi Arabia, from March 1, 2020, to May 31, 2020. We recorded clinical manifestations, laboratory test results, patient demographics, comorbidities, and treatments. Results The mean age of the study population was 46 years (88% were male, 12% were female), and 80% were non-Saudi. While most patients recovered and were discharged (n=603, 84.62%), 100 (13.99%) died due to COVID-19. Type 2 diabetes was present in 182 patients (79%) discharged and 45 patients (21%) who died. Hypertension was present in 26 (67%) discharged and 158 patients (81%) who died. Cardiovascular disease was present in 26 patients (67%) discharged and 13 (33%) who died. Chronic kidney disease was found in 11 patients (61%) discharged and six (33%) who died. Diarrhea was present in 11% of patients, nausea in 8%, and vomiting in 9% of patients. Twenty percent of patients had at least one GI symptom. Only 10% of those who died had GI symptoms, while 88% of those discharged had GI symptoms. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase, and γ-glutamyl transpeptidase were generally higher in the patients who died than in those who were discharged. Conclusions We noted an increase in at least one liver enzyme with no clinically significant acute liver injury or cases of acute liver failure as sequelae of COVID-19. However, the presence of injury at the time of admission resulted in a significantly higher mortality rate. Only a small number of patients infected with COVID-19 exhibited GI manifestations. The etiology of severe acute respiratory syndrome coronavirus 2-related GI involvement is due to multiple factors. It is not yet fully understood if GI manifestations are clinical signs of high viral loads or another physiological process. The clinical manifestation and laboratory test results indicate that COVID-19 impacts the hepatic system and GI tract, indicating that COVID-19 infection may risk liver and GI tract injury.

Contributions of energy pathways to ATP production and pH variations in postmortem muscles.

The roles of energy pathways in postmortem muscles are still debated. In this study, the contributions of different pathways to ATP production and pH variations were analyzed by using a kinetic model based on data from beef longissimus lumborum. Phosphocreatine represents over 92% of the initial ATP production but, after 24 h, glycolysis, phosphocreatine, myokinase reaction, and aerobic respiration contribute, respectively, 89.44%, 5.26%, 4.44%, and 0.86% of the cumulative amount of ATP produced. ATP hydrolysis and glycolysis result in 0.52 and 0.6 units of pH decline, respectively, at 24 h with ATP hydrolysis accounting for most of the early decline. Phosphocreatine, myokinase reaction, and aerobic respiration lead to, respectively, 0.08, 0.07, and 0.004 units of pH increase after 24 h though phosphocreatine is depleted within the first 30 min. Furthermore, electrical stimulation affects pH primarily through ATP hydrolysis and glycolysis. The initial muscle oxygen saturation level and phosphocreatine content affect pH but the influences are small.

Food insecurity and associated depression among older adults in India: evidence from a population-based study.

OBJECTIVE: The present study aimed to examine the associations of several indicators of food insecurity with depression among older adults in India. DESIGN: A cross-sectional study was conducted using country-representative survey data. SETTING AND PARTICIPANTS: The present study uses data of the Longitudinal Aging Study in India conducted during 2017-2018. The effective sample size for the present study was 31 464 older adults aged 60 years and above. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome variable was major depression among older adults. Descriptive statistics along with bivariate analysis was presented. Additionally, binary logistic regression analysis was used to establish the association between the depression and food security factors along with other covariates. RESULTS: The overall prevalence of major depression was 8.4% among older adults in India. A proportion of 6.3% of the older adults reduced the size of meals, 40% reported that they did not eat enough food of their choice, 5.6% mentioned that they were hungry but did not eat, 4.2% reported that they did not eat for a whole day and 5.6% think that they have lost weight due to lack of enough food in the household. Older adults who reported to have reduced the size of meals due to lack of enough food (adjusted OR (AOR): 1.76, CI 1.44 to 2.15) were hungry but did not eat (AOR: 1.35, CI 1.06 to 1.72) did not eat food for a whole day (AOR: 1.33; CI 1.03 to 1.71), lost weight due to lack of food (AOR: 1.57; CI 1.30 to1.89) had higher odds of being depressed in reference to their respective counterparts. CONCLUSION: The findings suggest that self-reported food insecurity indicators were strongly associated with major depression among older Indian adults. The national food security programmes should be enhanced as an effort to improve mental health status and quality of life among older population.

Cutaneous adverse reactions to coronavirus vaccines: A Saudi nationwide study.

The coronavirus vaccine was developed to help overcome the COVID-19 crisis. This study aimed to identify the cutaneous side effects secondary to Pfizer-BioNTech and Oxford-AstraZeneca COVID-19 vaccines in the general population of Saudi Arabia and to list the risk factors for the development of cutaneous side effects. This cross-sectional study was conducted in 2021, self-administered surveys were distributed electronically through social media, and telephonic interviews were conducted with a sample size of 1000 participants. Data analysis was performed using Statistical Package for the Social Sciences. A total of 1021 patients (229 male and 722 female) aged 12 years or older were included. While 833 participants were medically free, 188 had chronic illnesses. While 802 participants were not taking any medications, 219 were taking medications regularly. Oxford-Astra Zeneca and Pfizer BioNTech vaccines were administered to 319 and 702 participants, respectively. One-hundred and twenty-five participants previously had COVID-19 infection and 407 were exposed to a PCR positive case of COVID. Six hundred and fifty-nine patients (64.5%) reported experiencing injection site reactions: 606 (59.4%) had injection site pain, 168 (16.5%) had injection site swelling, and 107 (10.5%) had injection site redness. Only 51 patients (5%) experienced cutaneous side effects after injection. A significant association was found between chronic illnesses and cutaneous side effects post-vaccine (9% vs. 4.1%; p value = 0.005). Patients on medications showed a higher rate of symptoms (8.2% vs. 4.1%; p value = 0.005). Age, gender, vaccine types, and history of COVID-19 infection were not significantly associated with cutaneous side effects post-vaccine.

Types of household headship and associated life satisfaction among older adults in India: findings from LASI survey, 2017-18.

BACKGROUND: Household headship with decision-making power may have a positive influence on life satisfaction in older adults. This study examines the associations of several types of household headship with life satisfaction among older adults in India. METHOD: The study utilized the data from the Longitudinal Ageing Study in India (2017-18). The effective sample size for the study was 31,464 adults aged 60 years or older. Ordered logistic regression model was employed to find the association of life satisfaction with household headship status after adjusting for selected socioeconomic and demographic factors. RESULTS: It was found that about 1.3% of older male and 1.5% of older females had nominal headship status in their household. Higher percentage of older males (42%) and females (48.3%) who had nominal headship status had low life satisfaction. In multivariable analysis, older adults who practiced nominal headship had significantly higher odds of low life satisfaction in reference to older adults who practiced functional headship [Adjusted odds ratio (AOR): 1.87; confidence interval (CI): 1.45,2.42]. Interaction model reveals that older men who practised nominal headship had significantly higher odds of low life satisfaction in reference to older men who practised functional headship [AOR: 2.34; CI: 1.59,3.45]. Similarly, older women who practised nominal headship had 55% significantly higher likelihood to have low life satisfaction in reference to older men who practised functional headship [AOR: 1.55; CI: 1.09, 2.18]. CONCLUSION: The recognition of older individuals as active agents of the households they belong to, and giving them the value they deserve may help boosting their mental well-being. As a direct driver of subjective well-being, headship status and decision making power deserve a more prominent role and future studies are required on the mechanisms of functional and nominal headship statuses that have impact on successful aging.

Ultrasonication of beef improves calpain-1 autolysis and caspase-3 activity by elevating cytosolic calcium and inducing mitochondrial dysfunction.

The objective of this study was to investigate if ultrasonication of bovine longissimus thoracis et lumborum (LTL) steaks increases calpain-1 and caspase-3 activities, and if so, to explore the underlying mechanisms that trigger their activation. Post-rigor bovine LTL steaks were subjected to ultrasonication at 40 kHz and 12 W/cm2 for 40 min and subsequently aged for 14 d at 4 °C. Ultrasonication improved beef tenderness (P < 0.05) without negatively impacting pH, color, or cook loss (P > 0.05). Improved tenderness in the ultrasonicated steaks was associated with greater degradation of titin, desmin, troponin-T, and calpastatin and increased calpain-1 autolysis and caspase-3 activity (P < 0.05). In addition, ultrasonicated steaks had greater levels of cytosolic calcium and reactive oxygen species and lower mitochondrial oxygen consumption rate (P < 0.05). These data indicate that improved beef tenderness following ultrasonication is, in part, a function of increased calpain-1 and caspase-3 activities, potentially by elevating cytosolic calcium and inducing mitochondrial dysfunction, respectively.