Thermal robustness of signaling in bacterial chemotaxis.

Temperature is a global factor that affects the performance of all intracellular networks. Robustness against temperature variations is thus expected to be an essential network property, particularly in organisms without inherent temperature control. Here, we combine experimental analyses with computational modeling to investigate thermal robustness of signaling in chemotaxis of Escherichia coli, a relatively simple and well-established model for systems biology. We show that steady-state and kinetic pathway parameters that are essential for chemotactic performance are indeed temperature-compensated in the entire physiological range. Thermal robustness of steady-state pathway output is ensured at several levels by mutual compensation of temperature effects on activities of individual pathway components. Moreover, the effect of temperature on adaptation kinetics is counterbalanced by preprogrammed temperature dependence of enzyme synthesis and stability to achieve nearly optimal performance at the growth temperature. Similar compensatory mechanisms are expected to ensure thermal robustness in other systems.

Antioxidative and cardioprotective effects of minocycline in ischemia/reperfusion injury in experimental model of hypertension.

Cardiovascular diseases remains leading cause of death and disabilities. Coronary artery occlusion and consequent ischemia leads to acute myocardial infarction, but restoration of blood flow, paradoxically, provokes further myocardial damage known as reperfusion injury. Minocycline is possessing anti-inflammatory and anti-apoptotic activity, immune-modulating and antioxidative properties besides its primary antibacterial effect. Recently it gained significant interest in preventing cardiac damage especially due to myocardial ischemia/reperfusion injury (MI/RI). The aim of this study was to assess the protective ability of pre-treatment and post-treatment of isolated hearts from healthy and spontaneously hypertensive rats with minocycline, on functional recovery and redox status after MI/RI using Langendorff technique. Using sensor in the left ventricle, the cardiodynamic parameters were recorded and in the samples of the coronary venous effluent oxidative stress biomarkers were analyzed. Minocycline was injected directly into the coronary vessels, in pre-treatment 5 min before global ischemia, and in post-treatment during the first 5 min of reperfusion. Changes in redox balance induced by minocycline were more prominent in post-treatment fashion of application. Cardioprotective effects of minocycline due to MI/RI are even more significant in hypertensive hearts. Minocycline showed significant cardioprotective effects, which was more pronounced in hypertensive compared to healthy hearts. Reduction of pro-oxidative biomarkers was more prominent in hypertensive hearts compared to the normotensive, especially if it is applied in the form of post-treatment. Minocycline could be important tool in reduction of heart damage induced by MI/RI due to its antioxidative potential, if these results are confirmed by clinical study.

The effects of combustible cigarettes and electronic nicotine delivery systems on immune cell-driven inflammation and mucosal healing in ulcerative colitis.

INTRODUCTION: The effects of combustible cigarettes (CCs) and electronic nicotine delivery systems (ENDS) on immune cell-driven colon inflammation and intestinal healing of patients with ulcerative colitis (UC) are still unknown and, therefore, were examined in this study. METHODS: Intracellular staining and flow cytometry analysis of immune cells isolated from UC patients who used ENDS (UCENDS), CCs (UCCC) and who were non-smokers (UCAIR) were performed to elucidate cellular mechanisms which were responsible for CCs and ENDS-dependent modulation of immune response during UC progression. Additionally, dextran sulfate sodium (DSS)-colitis was induced in ENDS/CC/air-exposed mice (DSSENDS/ DSSCC/DSSAIR groups) to support clinical findings. RESULTS: Significantly increased number of immunosuppressive, IL-10, TGF-ß and IL-35-producing, FoxP3-expressing CD3+CD4+T regulatory cells (Tregs) was observed in the blood of UCENDS patients while reduced presence of inflammatory, TNF-α and IFN-γ-producing, Tbx21-expressing CD3+CD4+ Th1, IL-4-producing Gata3-expresing Th2 and IL-17, IL-22-producing, RORγT, IL-23R-expressing Th17 cells were noticed in the blood of UCCC patients. Exposure to either CCs or ENDS was associated with enhanced mucosal healing, ameliorated spontaneous recovery and improved survival of DSS-treated mice. An expansion of immunosuppressive cells (IL-10-producing tolerogenic CD11c+ dendritic cells, alternatively activated CD206, Arginase 1-expressing, IL-10-producing F4/80+macrophages, IL-10-producing FoxP3-expressing Tregs) was noticed in the colons of DSSENDS-treated mice, while reduced number of inflammatory, IL-17- and IL-4-producing T lymphocytes was observed in the colons of DSSCC-compared to DSSAIR-treated mice. CONCLUSIONS: Despite different mechanisms of action, both ENDS and CCs attenuated on-going colon inflammation, enhanced healing and ameliorated recovery of injured intestines of DSS-treated mice and UC patients. IMPLICATIONS: This is the first study that compared the effects of CCs and ENDS on immune cells of patients suffering from ulcerative colitis, providing new information about molecular and cellular mechanisms which were responsible for ENDS and CCs-dependent modulation of immune cell-driven colon injury and inflammation. Obtained results showed that both ENDS and CCs had capacity to attenuate detrimental immune response, enhanced healing and ameliorated recovery of injured intestines.

Oxidative stress and galectin-3 levels during skin grafting after hand injury: gender differences.

The study included 40 patients of both genders who underwent skin transplantation after a hand injury. The study aims to evaluate the oxidative stress parameters in patients' blood and serum levels of galectin-3 in order to investigate gender differences pre- and post- skin transplantation. The results of the study suggest a significant increase in superoxide anion radical levels, catalase activity, and reduced glutathione levels in females before skin transplantation. The surgical treatment caused significant increase in superoxide anion radical and hydrogen peroxide levels as prooxidants in males, while superoxide dismutase and catalase activity were also increased 7 days after the procedure. In females, superoxide anion radical and TBARS levels increased after surgical procedure as well as the activity of catalase. Regarding galectin-3 levels, a significant interaction between gender and time was observed (gender×time; p=0.000). Correlation analysis of different oxidative stress markers with gal-3 revealed the existence of a significant negative correlation of superoxide anion radical, catalase, and reduced glutathione with gal-3, but only in female patients. It can be concluded that OS as well as galectin-3 play important roles at least in the first 7 days of the postoperative period.

Left Ventricular Geometric Pattern Impacts QT Dispersion in Males Athletes and Sedentary Men.

AIM: To (1) compare QT dispersion (QTd) and echocardiographic features between athletes with concentric left ventricular (LV) hypertrophy, athletes with eccentric LV hypertrophy, and sedentary controls with a normal LV geometric pattern and (2) quantify associations between QTd and echocardiographic features within these groups. METHODS: Male athletes competing in different sports and sedentary men were stratified into groups according to their LV geometric pattern. These groups included eccentric LV hypertrophy (LV index > 115 g/m2, relative wall thickness [RWT] < 0.42) consisting of 38 athletes, concentric LV hypertrophy (LV index > 115 g/m2, RWT > 0.42) consisting of 40 athletes, and normal LV geometric pattern (LV index < 115 g/m2, RWT < 0.42) consisting of 40 sedentary controls. Following a cross-sectional design, participants underwent electrocardiographic (ECG) and echocardiographic screening. Data were compared between groups using one-way analyses of variance with Bonferroni post hoc tests. Associations between corrected QTd and echocardiographic variables were quantified using Pearson correlations. RESULTS: Alongside structural disparities between groups, corrected QTd was significantly (p < 0.001) lower in athletes with eccentric LV hypertrophy compared to athletes with concentric LV hypertrophy and sedentary controls. Significant, moderate-to-very-large correlations were found between corrected QTd and interventricular septal wall thickness in athletes with concentric (r = 0.416, p = 0.008) or eccentric LV hypertrophy (r = 0.734, p < 0.001), and sedentary controls (r = 0.464, p = 0.003). CONCLUSION: The provided comparative and relationship data may inform the development of more precise approaches for ECG and echocardiographic screening in athletes, particularly in those with concentric LV hypertrophy who may be at greater risk for developing prolonged QTd.

DNA interaction of selected tetrahydropyrimidine and its effects against CCl4-induced hepatotoxicity in vivo: Part II.

Tetrahydropyrimidine (compound A = methyl 4-[4'-(heptyloxy)-3'-methoxyphenyl]-1,6-dimethyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate) was chosen for in vivo studies after exhibiting noteworthy in vitro activity against the K562 and MDA-MB-231 cell lines, with IC50 values of 9.20 ± 0.14 µM and 12.76 ± 1.93 µM, respectively. According to experimental (fluorescence titration, viscosity, and differential scanning calorimetry) results, A interacts with DNA via the minor groove. In vivo, acute oral toxicity studies in Wistar albino rats proved no noticeable symptoms of either toxicity or death during the follow-up period. Genotoxic and antigenotoxic studies at three different concentrations of A (5, 10, and 20 mg/kg of body weight) in Wistar albino rats showed that the dose of 5 mg/kg body weight did not cause DNA damage and had a remarkable DNA protective activity against CCl4-induced DNA damage, with a percentage reduction of 78.7%. It is also important to note that, under the investigated concentrations of A, liver damage is not observed. Considering all experimental outcomes realized under various in vivo investigations (acute oral toxicity, genotoxicity, antigenotoxicity, and biochemical tests), compound A could be a promising candidate for further clinical testing.

Diallyl Trisulfide and Cardiovascular Health: Evidence and Potential Molecular Mechanisms.

Traditionally, garlic has a valuable role in preventing and reducing the incidence of many diseases and pathophysiological disorders. Consequently, some researchers have focused on the beneficial cardiovascular properties of diallyl trisulfide (DATS), the most potent polysulfide isolated from garlic. Therefore, in this review, we collected the available data on DATS, its biochemical synthesis, metabolism and pharmacokinetics, and gathered the current knowledge and the role of DATS in cardiovascular diseases. Overall, this review summarizes the cardioprotective effects of DATS and brings together all previous findings on its protective molecular mechanisms, which are mainly based on the potent anti-apoptotic, anti-inflammatory, and antioxidant potential of this polysulfide. Our review is an important cornerstone for further basic and clinical research on DATS as a new therapeutic agent for the treatment of numerous heart diseases.

Hypotensive and Cardioprotective Potential of Yellow Bedstraw Extract-Based Oral Liquid in Spontaneously Hypertensive Rats.

This study aimed to prepare, characterize and assess the antioxidant activity of yellow bedstraw extracts (YBEs), focusing on identifying extracts with high antioxidant capacity. The selected extract was loaded into an oral liquid formulation and further investigated for its therapeutic potential in reducing blood pressure and associated complications in spontaneously hypertensive Wistar kyoto rats (SHR). Rats were divided into untreated SHR and SHR treated with a YBE-based oral formulation over four weeks. After treatment, blood pressure was measured, and cardiac function was assessed using the Langendorff technique to simulate ex vivo ischemic conditions. Prooxidant levels were assessed in plasma while antioxidant activity was evaluated in red blood cells. Histological analyses of heart, kidney, and liver samples were conducted to assess pathological changes induced by hypertension. Our results showed that the oral formulation loaded with ethanol YBE effectively reduced blood pressure, preserved myocardial function under ischemic stress, and decreased oxidative stress markers in blood. Importantly, our formulation with YBE demonstrated potential in attenuating structural kidney damage associated with hypertension. Overall, these findings suggest a cardioprotective effect of orally administered YBE formulation, highlighting its potential as an herbal supplement. However, clinical studies are warranted to validate these findings and explore the extract's suitability for clinical use.

Potentilla tormentilla Extract Loaded Gel: Formulation, In Vivo and In Silico Evaluation of Anti-Inflammatory Properties.

The objective of the study was to develop a novel topical gel by mixing Potentilla tormentilla ethanolic extract, thermosensitive poloxamer 407, and carbomer 940 and evaluating its stability and rheological behavior. The irritation potential of the gel was evaluated in accordance with the Organization for Economic Cooperation and Development Guidelines 404. The potential anti-inflammatory effects of the developed gel were evaluated in vivo in rats using the carrageenan-induced paw edema test. Moreover, the in silico binding affinity for chlorogenic and ellagic acid, as dominant components in the extract, against cyclooxygenase (COX) 1 and 2 was also determined. Our findings suggest that the gel containing Potentilla tormentilla extract remained stable throughout the observation period, exhibited pseudoplastic behavior, and caused no irritation in rats, thus being considered safe for topical treatment. Additionally, the developed gel showed the capability to reduce rat paw edema, which highlights significant anti-inflammatory potential. In silico analysis revealed that chlorogenic and ellagic acid exhibited a reduced binding affinity against COX-1 but had a similar inhibitory effect on COX-2 as flurbiprofen, which was confirmed by molecular dynamics results. The study proposes the possible application of Potentilla tormentilla ethanolic extract gel for the alleviation of localized inflammatory diseases; however, future clinical evaluation is required.

A comparison in knee flexor and extensor strength following ACL reconstruction in international, male soccer players receiving patellar tendon or hamstrings grafts.

The aim of this study was to compare knee extensor and flexor strength recovery following anterior cruciate ligament (ACL) reconstruction between bone-patellar tendon-bone (BPTB) and hamstring tendon (HT) grafts in international male soccer players undergoing comparable 6-month rehabilitation programmes. Seventeen players underwent ACL reconstruction with either an autogenous BPTB graft or HT graft. Knee extensor and flexor peak torques were measured at 3 months and 6 months in the injured and contralateral legs following surgery using isokinetic dynamometry. The moderate-large asymmetries in knee extensor peak torque between legs at 3 months across graft types (BPTB: p = 0.002, g = -0.94; HT: p = 0.02, g = -0.55) were reduced to trivial asymmetries at 6 months (BPTB: p = 0.30, g = -0.19; HT: p = 0.40, g = -0.16), with a non-significant difference in limb symmetry index (LSI) between grafts at 6 months (p = 0.62, g = -0.24). Similarly, moderate-large asymmetries in knee flexor peak torque between legs at 3 months across graft types (BPTB: p = 0.13, g = -0.50; HT: p = 0.01, g = -0.97) were reduced to trivial-small asymmetries at 6 months (BPTB: p = 0.25, g = 0.18; HT: p = 0.01, g = -0.47); however, a superior LSI was evident with BPTB compared to HT grafts at 6 months (p = 0.007, g = 1.43, large). Strength and conditioning professionals working with soccer players who are rehabilitating from ACL reconstruction after receiving a HT graft should give adequate attention to delivering suitable hamstring exercises that ensure optimal strength restoration.

Its all about IFN-λ4: Protective role of IFNL4 polymorphism against COVID-19-related pneumonia in females.

Despite the pivotal role of IFN-λs in the innate immune response, the data on its genetic polymorphism in relation to COVID-19 severity are scarce and contradictory. In the present study, we aimed to determine if the presence of the most frequent functional single nucleotide polymorphisms (SNPs) of the two most important IFN-λs coding genes, namely IFNL3 and IFNL4, alters the likelihood of SARS-CoV-2-infected patients to develop more severe form of the disease. This observational cohort study involved 178 COVID-19 patients hospitalized at the University Clinical Centre Kragujevac, Serbia. Patients' demographics, clinical characteristics, and laboratory parameters were collected at admission. COVID-19 signs and symptoms were assessed during the hospital stay, with the worst condition determining the disease severity. Genotyping for IFNL3 (rs12980275 and rs8099917) and IFNL4 (rs12979860 and rs368234815) SNPs was conducted using TaqMan assays. Our study revealed carriers of IFNL3 and IFNL4 minor alleles to be less likely to progress from mild to moderate COVID-19, that is, to develop COVID-19-related pneumonia. After adjustment for other factors of influence, such as age, sex, and comorbidities, the likelihood of pneumonia development remained significantly associated with IFNL4 polymorphism (odds ratios [ORs] [95% confidence interval (95% CI)]: 0.233 [0.071; 0.761]). When the patients were stratified according to sex, the protective role of IFNL4 minor alleles, controlled for the effect of comorbidities, remained significant only in females (OR [95% CI]: 0.035 [0.003; 0.408]). Our results strongly suggest that IFNL4 rs12979860 and rs368234815 polymorphisms independently predict the risk of COVID-19-related pneumonia development in females.

IFNL3/4 polymorphisms as a two-edged sword: An association with COVID-19 outcome.

Coronavirus Disease 2019 (COVID-19) has been ranked among the most fatal infectious diseases worldwide, with host's immune response significantly affecting the prognosis. With an aim to timely predict the most likely outcome of SARS-CoV-2 infection, we investigated the association of IFNL3 and IFNL4 polymorphisms, as well as other potentially relevant factors, with the COVID-19 mortality. This prospective observational case-control study involved 178 COVID-19 patients, hospitalized at Corona Center or Clinic for Infectious Diseases of University Clinical Centre Kragujevac, Serbia, followed up until hospital discharge or in-hospital death. Demographic and clinical data on all participants were retrieved from the electronic medical records, and TaqMan assays were employed in genotyping for IFNL3 and IFNL4 single nucleotide polymorphisms (SNPs), namely rs12980275, rs8099917, rs12979860, and rs368234815. 21.9% and 65.0% of hospitalized and critically ill COVID-19 patients, respectively, died in-hospital. Multivariable logistic regression analysis revealed increased Charlson Comorbidity Index (CCI), N/L, and lactate dehydrogenase (LDH) level to be associated with an increased likelihood of a lethal outcome. Similarly, females and the carriers of at least one variant allele of IFNL3 rs8099917 were almost 36-fold more likely not to survive SARS-CoV-2 infection. On the other hand, the presence of at least one ancestral allele of IFNL4 rs368234815 decreased more than 15-fold the likelihood of mortality from COVID-19. Our results suggest that, in addition to LDH level, N/L ratio, and CCI, IFNL4 rs368234815 and IFNL3 rs8099917 polymorphisms, but also patients' gender, significantly affect the outcome of COVID-19.

Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems.

We describe the preparation, dynamic, assembly characteristics of vase-shaped basket 13- along with its ability to form an inclusion complex with anticancer drug mitoxantrone in abiotic and biotic systems. This novel cavitand has a deep nonpolar pocket consisting of three naphthalimide sides fused to a bicyclic platform at the bottom while carrying polar glycines at the top. The results of 1 H Nuclear Magnetic Resonance (NMR), 1 H NMR Chemical Exchange Saturation Transfer (CEST), Calorimetry, Hybrid Replica Exchange Molecular Dynamics (REMD), and Microcrystal Electron Diffraction (MicroED) measurements are in line with 1 forming dimer [12 ]6- , to be in equilibrium with monomers 1(R) 3- (relaxed) and 1(S) 3- (squeezed). Through simultaneous line-shape analysis of 1 H NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket 1(R) 3- includes anticancer drug mitoxantrone (MTO2+ ) in its pocket to give stable binary complex [MTO⊂1]- (Kd =2.1 µM) that can be precipitated in vitro with UV light or pH as stimuli. Both in vitro and in vivo studies showed that the basket is nontoxic, while at a higher proportion with respect to MTO it reduced its cytotoxicity in vitro. With well-characterized internal dynamics and dimerization, the ability to include mitoxantrone, and biocompatibility, the stage is set to develop sequestering agents from deep-cavity baskets.

Transforming growth factor beta 1 (TGF-ß1) in COVID-19 patients: relation to platelets and association with the disease outcome.

Transforming growth factor beta (TGF-ß) is a ubiquitously distributed cytokine known to contribute to the pathogenesis of numerous pathological processes. The aim of this study was to measure serum concentrations of TGF-ß1 in severely ill COVID-19 patients and to analyze its relationship with selected hematological and biochemical parameters and with the disease outcome. The study population included 53 COVID-19 patients with severe clinical expression of the disease and 15 control subjects. TGF-ß1 was determined in serum samples and supernatants from PHA-stimulated whole blood cultures using ELISA assay. Biochemical and hematological parameters were analyzed using standard accepted methods. Our results showed that serum levels of TGF-ß1 in COVID-19 patients and controls correlate with the platelet counts. Also, positive correlations of TGF-ß1 with white blood cell and lymphocyte counts, platelet-to-lymphocyte (PLR) ratio, and fibrinogen level were shown, while negative correlations of this cytokine with platelet distribution width (PDW), D-dimer and activated partial thromboplastin time (a-PTT) values in COVID-19 patients were observed. The lower serum values of TGF-ß1 were associated with the unfavorable outcome of COVID-19. In conclusion, TGF-ß1 levels were strongly associated with platelet counts and unfavorable disease outcome of severely ill COVID-19 patients.

The impact of different diuretics on regression of myocardial reperfusion injury in spontaneously hypertensive rats.

The study's objective was to ascertain the results of sub-chronic therapy of various diuretics on the ischemia/reperfusion dysfunction of the heart in hypertensive rats by a global ischemia in an isolated rat heart model. The research included 40 spontaneously hypertensive male rats (Wistar Kyoto strain, body mass 250 ± 30 g, 8 weeks old) grouped into four groups. The animals were treated for 4 weeks with 10 mg/kg of hydrochlorothiazide, indapamide, or spironolactone per os. After a period of sub-chronic treatment, we analyzed hemodynamic measurements, echocardiography, and myocardial function according to the Langendorff retrograde perfusion method. The hearts were subjected to 20 min of global ischemia and then reperfused for 30 min (I20:R30). Cardiovascular parameters that depict the left ventricle functions were continuously monitored, while flowmetry was used to determine coronary flow values. Markers of oxidative stress were estimated from coronary venous effluent using spectrophotometry. All three examined diuretics (hydrochlorothiazide, spironolactone, indapamide) lowered the production of the majority of the detected prooxidants, reducing myocardial oxidative damage. The cardiological examination of heart function in vivo demonstrated that treatment with indapamide and spironolactone mitigates left ventricular hypertrophy but without significant lowering of blood pressure or increment in ejection fraction. Additionally, monitoring of cardiac function ex vivo indicated the cardiodepressant effect of spironolactone in spontaneously hypertensive rats.

Effects of direct pulp capping with recombinant human erythropoietin and/or mineral trioxide aggregate on inflamed rat dental pulp.

OBJECTIVE: This study aimed to evaluate the dental pulp responses to recombinant human erythropoietin (rhEPO) and/or mineral trioxide aggregate (MTA) in pulp capping of inflamed dental pulp in vivo. MATERIALS AND METHODS: In accordance with ARRIVE guidelines, pulp inflammation was induced by exposing the maxillary first molars (n = 64) of Wistar rats (n = 32) to the oral environment for two days. The exposed pulps were randomly assigned four groups based on the pulp capping material: rhEPO, MTA, MTA + rhEPO, or an inert membrane. An additional eight rats formed the healthy control group. After four weeks, the animals were euthanized, and histological, qRT-PCR, and spectrophotometric techniques were employed to analyze the left maxillary segments, right first maxillary molars, and blood samples, respectively. Statistical significance was set at p < 0.05 and < 0.001. RESULTS: Pulp capping with rhEPO, MTA, or MTA + rhEPO resulted in lower inflammation and higher mineralization scores compared to untreated control. MTA + rhEPO group exhibited significantly decreased expression of tumor necrosis factor-alpha, and interleukin 1-beta, while MTA group showed substantially reduced expression of interferon-gamma. Both rhEPO and MTA + rhEPO groups presented elevated dentin matrix protein 1 levels compared to untreated control. Furthermore, pulp capping with rhEPO and/or MTA led to increased transforming growth factor-beta 1 expression and reductions of pro-inflammatory/immunoregulatory cytokine ratios and prooxidative markers. Pulp capping with rhEPO also resulted in increase of systemic antioxidative stress markers. CONCLUSION: Capping with rhEPO or MTA + rhEPO resulted in a favorable effect that was similar or even superior to that of MTA.

Sacubitril/valsartan reverses cardiac structure and function in experimental model of hypertension-induced hypertrophic cardiomyopathy.

This study evaluated the effect of sacubtril/valsartan on cardiac remodeling, molecular and cellular adaptations in experimental (rat) model of hypertension-induced hypertrophic cardiomyopathy. Thirty Wistar Kyoto rats, 10 healthy (control) and 20 rats with confirmed hypertension-induced hypertrophic cardiomyopathy (HpCM), were used for this study. The HpCM group was further subdivided into untreated and sacubitril/valsartan-treated groups. Myocardial structure and function were assessed using echocardiography, Langendorff's isolated heart experiment, blood sampling and qualitative polymerase chain reaction. Echocardiographic examinations revealed protective effects of sacubitril/valsartan by improving left ventricular internal diameter in systole and diastole and fractional shortening. Additionally, sacubitril/valsartan treatment decreased systolic and diastolic blood pressures in comparison with untreated hypertensive rats. Moreover, sacubitril/valsartan treatment reduced oxidative stress and apoptosis (reduced expression of Bax and Cas9 genes) compared to untreated rats. There was a regular histomorphology of cardiomyocytes, interstitium, and blood vessels in treated rats compared to untreated HpCM rats which expressed hypertrophic cardiomyocytes, with polymorphic nuclei, prominent nucleoli and moderately dilated interstitium. In experimental model of hypertension-induced hypertrophic cardiomyopathy, sacubitril/valsartan treatment led to improved cardiac structure, haemodynamic performance, and reduced oxidative stress and apoptosis. Sacubitril/valsartan thus presents as a potential therapeutic strategy resulted in hypertension-induced hypertrophic cardiomyopathy.

The incidence rate of ACL injuries and ankle sprains in basketball players: A systematic review and meta-analysis.

OBJECTIVE: To quantify the incidence rate of anterior cruciate ligament (ACL) injuries and ankle sprains according to player sex, playing level, and exposure setting (training vs. games) in basketball players. METHODS: PubMed, MEDLINE, Google Scholar, and ScienceDirect were searched. Only studies reporting the number of ACL injuries and/or ankle sprains alongside the number of athlete-exposures (training sessions and/or games) in basketball players were included. RESULTS: Thirty studies (17 reporting ACL injuries and 16 reporting ankle sprains) were included in the meta-analysis. Higher (p < 0.05) ACL injury incidence rates per 1000 athlete-exposures were recorded in females (female: 0.20 95% confidence intervals [0.16-0.25]; male: 0.07 [0.05-0.08]; female-to-male ratio: 3.33 [3.10-3.57]), in players competing at higher playing levels (amateur: 0.06 [0.04-0.09]; intermediate: 0.16 [0.13-0.20]; elite: 0.25 [0.14-0.64]), and in games (games: female, 0.27 [0.21-0.32]; male, 0.06 [0.03-0.08]; training: female, 0.03 [0.02-0.05]; male: 0.01 [0.00-0.02]; game-to-training ratio: 7.90 [4.88-12.91]). Higher (p < 0.05) ankle sprain incidence rates per 1000 athlete-exposures were observed in males (female: 0.82 [0.61-1.03]; male: 0.90 [0.61-1.19]; female-to-male ratio: 0.91 [0.83-0.99]), in players competing at higher playing levels (amateur: 0.54 [0.51-0.57]; intermediate: 1.12 [1.00-1.24]; elite: 1.87 [1.29-2.46]), and in games (games: 2.51 [1.85-3.16]; training: 0.80 [0.52-0.80]; game-to-training ratio: 2.77 [2.35-3.26]). CONCLUSION: According to player sex, ACL injury incidence rate is higher in females, while ankle sprain incidence rate is greater in males. ACL injury and ankle sprain incidence rates are greater in players competing at higher playing levels and during games compared to training.

Molecular Mechanisms Responsible for Mesenchymal Stem Cell-Based Modulation of Obstructive Sleep Apnea.

Mesenchymal stem cells (MSCs) are adult stem cells that reside in almost all postnatal tissues where, due to the potent regenerative, pro-angiogenic and immunomodulatory properties, regulate tissue homeostasis. Obstructive sleep apnea (OSA) induces oxidative stress, inflammation and ischemia which recruit MSCs from their niches in inflamed and injured tissues. Through the activity of MSC-sourced anti-inflammatory and pro-angiogenic factors, MSCs reduce hypoxia, suppress inflammation, prevent fibrosis and enhance regeneration of damaged cells in OSA-injured tissues. The results obtained in large number of animal studies demonstrated therapeutic efficacy of MSCs in the attenuation of OSA-induced tissue injury and inflammation. Herewith, in this review article, we emphasized molecular mechanisms which are involved in MSC-based neo-vascularization and immunoregulation and we summarized current knowledge about MSC-dependent modulation of OSA-related pathologies.

Isokinetic Muscle Strength in Elite Soccer Players 3 and 6 months After Anterior Cruciate Ligament Reconstruction.

ABSTRACT: Milutinovic, A, Jakovljevic, V, Dabovic, M, Faude, O, Radovanovic, D, and Stojanovic, E. Isokinetic muscle strength in elite soccer players 3 months and 6 months after anterior cruciate ligament reconstruction. J Strength Cond Res 37(4): e297-e304, 2023-The aim of this study was to evaluate interlimb symmetry in quadriceps and hamstring peak torque of elite soccer players at 3 months (stage 1) and 6 months (stage 2) after anterior cruciate ligament (ACL) reconstruction. Eight male professional soccer players competing at the highest level across different European countries, who had undergone ACL reconstruction, participated in this study. All patients underwent a supervised physiotherapy program after surgery. Data analyses included the use of separate two-way repeated-measures analyses of variance and effect sizes. Although knee extensor and flexor strength of the non-injured limb was found to be relatively unaltered ( g = -0.10 to 0.00) between stage 1 and stage 2, comparisons across time points revealed moderate improvements in quadriceps peak torque ( p = 0.01, g = 0.52), hamstring peak torque ( p = 0.07, g = 0.51), and hamstring:quadriceps (H/Q) ratio ( p = 0.03, g = -0.68) of the injured leg, as well as small-large improvements in the quadriceps ( p = 0.004, g = 1.24) and hamstring limb symmetry index (LSI) ( p = 0.056, g = 0.41). A time-dependent moderate-large asymmetry observed at stage 1 between the injured and noninjured leg in quadriceps peak torque ( p < 0.001, g = -1.83), hamstring peak torque ( p = 0.157, g = -0.67), and the H:Q ratio ( p = 0.06, g = 1.01), as well as between the hamstring and quadriceps LSI ( p = 0.03, g = -0.74) was eliminated at stage 2 ( g = -0.31 to 0.42). Our findings indicate the importance of supervised and comprehensive therapy, as well as strength screening to assist in recovery aimed at optimizing identified strength deficits following ACL reconstruction.