Stress Injury Research Articles

Glomerular Elasticity and Gene Expression Patterns Define Two Phases of Alport Nephropathy.

Early steps in glomerular injury are poorly understood in collagen IV nephropathies. We characterized structural, functional, and biophysical properties of glomerular capillaries and podocytes in Col4α3-/- mice and analyzed kidney cortex transcriptional profiles at various disease stages. We investigated the effects of TUDCA (suppresses ER stress) on these parameters and used human FSGS transcriptomic data to identify pathways rescued by TUDCA. In Col4α3-/- mice, podocyte injury develops by 3 months, with maximum glomerular deformability and 40% podocyte loss at 4 months. This period is followed is followed by glomerular capillary stiffening, proteinuria, reduced renal function, inflammatory infiltrates, and fibrosis. Bulk RNA sequencing at sequential time points revealed progressive increases in inflammatory and injury gene expression, and activation of the TNF pathway. Mapping Podocyte-enriched genes from FSGS patients to mice showed that TUDCA, which mitigated renal injury suppressed molecular pathways associated with podocyte stress, hypertrophy and tubulo-interstitial injury. Col4α3-/- nephropathy progresses in two phases. The first is characterized by podocytopathy, increased glomerular capillary deformability and accelerated podocyte loss, and the second by increased capillary wall stiffening and renal inflammatory and profibrotic pathway activation. The response of podocytes to TUDCA treatment provides insights into signaling pathways in Alport and related nephropathies.

PDK4-mediated Nrf2 inactivation contributes to oxidative stress and diabetic kidney injury

Diabetic kidney disease (DKD) is often featured with redox dyshomeostatis. Pyruvate dehydrogenase kinase 4 (PDK4) is the hub for DKD development. However, the mechanism by which PDK4 mediates DKD is poorly understood. The current work aimed to elucidate the relationship between PDK4 and DKD from the perspective of redox manipulation. Oxidative stress was observed in the human proximal tubular cell line (HK-2 cells) treated with a high concentration of glucose and palmitic acid (HGL). The mechanistic study showed that PDK4 could upregulate Kelch-like ECH-associated protein 1 (Keap1) in HGL-treated HK-2 cells through the suppression of autophagy, resulting in the depletion of nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of redox homeostasis. At the cellular level, pharmacological inhibition or genetic knockdown of PDK4 could boost Nrf2, followed by the increase of a plethora of antioxidant enzymes and ferroptosis-suppression enzymes. Meanwhile, the inhibition or knockdown of PDK4 remodeled iron metabolism, further mitigating oxidative stress and lipid peroxidation. The same trend was observed in the DKD mice model. The current work highlighted the role of PDK4 in the development of DKD and suggested that PDK4 might be a promising target for the management of DKD.

Effect of Exercise Regimens on Musculoskeletal Health in Working Horses in Bangladesh

Purpose: To aim of the study was to analyze the effect of exercise regimens on musculoskeletal health in working horses in Bangladesh. Methodology: This study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low cost advantage as compared to a field research. Our current study looked into already published studies and reports as the data was easily accessed through online journals and libraries. Findings: Recent studies on exercise regimens for working horses in Bangladesh show that regular, moderate-intensity exercise strengthens muscles and bones, reducing strains and sprains. Structured training enhances bone density and tendon strength, crucial for their physical demands. Exercise also prevents conditions like osteoarthritis by maintaining joint mobility. Muscle conditioning improves strength and flexibility, lowering the risk of injuries. Varied exercise routines promote balanced musculoskeletal development and endurance. Unique Contribution to Theory, Practice and Policy: Biomechanical theory, physiological adaptation theory & workload management theory may be used to anchor future studies on effect of exercise regimens on musculoskeletal health in working horses in Bangladesh. Implement balanced exercise programs that mix high-intensity and low-intensity activities, and ensure shorter, frequent exercise sessions to promote muscle recovery and reduce overuse injuries. Establish regulations that limit the maximum workload and duration of work for horses, ensuring that they are not subjected to continuous high-intensity tasks without adequate rest.

PDK4-mediated Nrf2 inactivation contributes to oxidative stress and diabetic kidney injury

Diabetic kidney disease (DKD) is often featured with redox dyshomeostatis. Pyruvate dehydrogenase kinase 4 (PDK4) is the hub for DKD development. However, the mechanism by which PDK4 mediates DKD is poorly understood. The current work aimed to elucidate the relationship between PDK4 and DKD from the perspective of redox manipulation. Oxidative stress was observed in the human proximal tubular cell line (HK-2 cells) treated with a high concentration of glucose and palmitic acid (HGL). The mechanistic study showed that PDK4 could upregulate Kelch-like ECH-associated protein 1 (Keap1) in HGL-treated HK-2 cells through the suppression of autophagy, resulting in the depletion of nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of redox homeostasis. At the cellular level, pharmacological inhibition or genetic knockdown of PDK4 could boost Nrf2, followed by the increase of a plethora of antioxidant enzymes and ferroptosis-suppression enzymes. Meanwhile, the inhibition or knockdown of PDK4 remodeled iron metabolism, further mitigating oxidative stress and lipid peroxidation. The same trend was observed in the DKD mice model. The current work highlighted the role of PDK4 in the development of DKD and suggested that PDK4 might be a promising target for the management of DKD.

O-177 Emotional experiences of staff caring for parents suffering a pregnancy loss

Abstract Experiencing pregnancy loss can have devastating emotional impacts on expectant parents, leading them to experience depression, anxiety and post-traumatic stress. There is now a well-established literature into the experiences of expectant parents, with dozens of studies conducted since the 1990s. However, over this period there has been notably less research conducted into the experiences of the professionals who care for these women. Addressing this is crucial; healthcare professionals are the greatest asset that healthcare systems have. Providing better support for them is the best route to improving care for expectant parents. The studies which have been conducted suggest the emotional toll on professionals can be significant. Emotions described can reflect those of expectant parents, including sadness, grief, and anger. One study suggested that delivering this care can be like ‘working in darkness’; another found that delivering news of losses to expectant parents on a regular basis can cause an emotional ‘repetitive strain injury’ for some. This talk will tackle this topic, providing updates and insights from recent studies which have investigated the experiences of healthcare professionals who undertake the emotional work of caring for expectant parents who are experiencing loss. It will take an interactive approach, using audience feedback to understand and learn from the experiences shared by those in the room. The importance and value of professionals who work in this area will be highlighted; coping strategies and self-care activities will be considered.

A Comparative Study between Vacuum-Assisted Closure (VAC) versus Plaletets Rich Plasma (PRP) for Dressing of Diabetic Foot Ulcers

Abstract Background Diabetic foot ulcers are among the most generally perceived troubles of patients who have diabetes mellitus which isn't particularly controlled. It is commonly the outcome of poor glycemic control, stowed away neuropathy, periphery vascular sickness, or sad foot care. It is similarly one of the typical justification for osteomyelitis of the foot and evacuation of lower uttermost focuses. These ulcers are ordinarily in the space of the foot which encounters repetitive injury and strain sensations. Objective To evaluate the effect of plasma rich platelets versus vacuum-assisted-closure dressing in the improvement of the healing process in diabetic foot ulcer. Patients and Methods The survey included 40 patients who had continuous diabetic foot ulcer and were treated at the piece of Vascular and General an operation, Ain Scams School Facilities and Luxor Overall Crisis center, Cairo, Egypt. Starting from December 2021 to May 2022. Results Larger piece of the patients in both control and cases had discharge. (Patients with sickness or purulent delivery were barred from study). In our examination of 40 patients the ulcer size went from 6 to 15 cm2. The mean size in pack (A) was 9.48±1.91 cm2 and among Get-together (B) 9.56 ±1.87 cm2. In our survey we saw that recovering in cases or exploratory get-together took in a general sense less time when differentiated and bundle (A). The mean length of retouching in control pack was 7.3 ±1.91 weeks and mean term of recovering for pack (B) was 4.38±1.94 weeks. The probability regard (p regard) gained ensuing to applying unpaired t test for the above data arises to be 0.0001 which is really gigantic. Conclusion Our case series showed that PRP and VAC is a secured and strong treatment technique for consistent non-retouching ulcers. Using PRP to treat persevering wounds/ulcers might further develop patching, yet also thwart lower limit evacuations achieved by non-recovering injuries. Appropriately, further investigation and randomized controlled clinical starters on greater patient people are essential to endorse the results.

Could footwear stiffness reduce the development of proinflammatory markers in long-distance runners?

PurposeStrenuous running triggers the coordination of pro- and anti-inflammatory, as well as immunoregulatory cytokines, which are upregulated in response to inflammatory stimulus and thus considered a precursor to overuse injury. The aim of this study was to correlate injury risk to footwear stiffness normalized against each runner’s weight, i.e. the midsole’s ability to resist deformation in response to the applied force. Materials and methodsExperienced runners participated in a 2h 15 min intensity-controlled run, averaging 85% of their threshold heart rate. Venous blood, collected in the field prior to and immediately after the race, was subjected to multi-parameter flow cytometry, to monitor the plasma levels of interleukin (IL)-2, IL-6 and tumor necrosis factor alpha (TNFα). Footwear stiffness was determined utilizing an automated drop test, recreating footfall pattern, impact speed and weight of each runner. Plasma level increase was analyzed for each cytokine, using one-way ANOVA and the data associated to footwear stiffness through the calculation of Pearson correlation coefficient. ResultsOnly IL-6 levels exhibited a statistical significant increase pre- to post-race, corresponding to F(1,8)=24.0417 with a critical value of 4.4139. The increase in IL-6 levels was also found to produce a strong correlation to footwear stiffness, expressed in a Pearson coefficient of r(8)=0.79 at ρ=0.0063 (P < 0.05). ConclusionThe significant increase in pro-inflammatory markers, such as IL-6 which are associated with injury, would suggest that runners using compliant footwear are at lower risk of overuse injury than the ones running on stiffer midsoles.

Musculoeskeletal injuries and illnesses in the Spanish and French trail running teams during the WMTRC 2023

IntroductionAs a result of the recent professionalization of trail running, the epidemiology of injury and illness of professional athletes is still unknown. The aim of the study is to describe the epidemiology of musculoskeletal injuries and illnesses among professional trail runners of two national teams participating at the World Mountain and Trail Running Championships 2023. Material and MethodsThe study included 77 professional trail running athletes from Spanish and French National Teams that competed in the Championships. Data of injuries and illnesses were recorded in “Daily Medical Report on Injuries and Illnesses” form, designed according to the recommendations of the International Olympic Committee consensus statement. ResultsThirty-eight percent of the athletes had an injury or illness; of them 22 % suffered an injury and 16 % an illness. Regarding sport performance, 24 % of the athletes suffered an injury and illness that affect their sport performance and 12 % had to withdraw due to a major injury or illness. By anatomical location foot is the most affected and hyperthermia and dehydration are the most frequent aetiology of illness. ConclusionsMore than one third of professional trail running athletes suffered an injury or illness during the World Championship and around one in ten were unable to finish the competition due to a major injury or illness. The principal cause of withdrawal is dehydration, followed by overuse injuries and acute traumas.

Ginsenoside Rg1 reduces cardiac inflammation against myocardial ischemia/reperfusion injury by inhibiting macrophage polarization

BackgroundMyocardial ischemia/reperfusion (MI/R) injury is the main cause of death worldwide and poses a significant threat to cardiac health. Ginsenoside Rg1 has been shown to have inhibitory effects on inflammatory activation, oxidative stress, and cardiac injury, suggesting that Rg1 may have therapeutic effects on MI/R injury. However, the mechanism remains to be further studied. Materials and methodsLeft anterior descending coronary artery ligation was performed in Sprague-Dawley rats to construct an MI/R model in vivo. Organ index, electrocardiogram, infarct size, histopathological changes, and detection of cardiac injury and inflammatory factors in the rats were used to evaluate myocarditis, macrophage polarization, and fibrosis. We also used rat bone marrow-derived macrophages (BMDMs) to further investigate the effects of Rg1 on absent in melanoma 2 (AIM2) activation and macrophage polarization in vitro. ResultsAdministration of Rg1 exhibited dose-dependent cardioprotective effects and effectively reduced MI/R injury. Rg1 significantly attenuated myocardial inflammation and inhibited M1 macrophage polarization during MI/R injury. Furthermore, Rg1 significantly reduced cardiac fibrosis in response to MI/R injury. This anti-fibrotic effect may contribute to the preservation of cardiac structure and function following an ischemic insult. Meanwhile, Rg1 effectively inhibited the activation of the AIM2 inflammasome in vitro, highlighting its potential as a key regulator of inflammatory pathways. ConclusionOur findings elucidate the multifaceted mechanisms underlying Rg1's cardioprotective effects, including its ability to mitigate inflammation, modulate macrophage polarization, and inhibit fibrosis.

The effect of fresh and used ankle taping on lower limb biomechanics in sports specific movements

ObjectivesThis study aimed to investigate the effects of ankle taping on lower extremity joint kinetics and kinematics related to injury development and how these effects change after sports-specific use of the tape. DesignRandomized, repeated measures design with three conditions: Barefoot (BF), tape applied fresh (TF), and tape after sports-specific use (TU) with sex as between-subject factor. MethodsTwenty-five healthy participants (ten female) performed sports-specific movements, including running (RUN), drop jumping (DJ), and 180° change of direction (COD), under the three conditions. Kinetic and kinematic data were collected using 3D motion capturing and force platforms. ResultsTF and TU significantly reduced peak ankle inversion during sports-specific movements. Biomechanical risk factors for ACL or running overuse injuries were either unchanged or decreased with TF, with the exception of the peak loading rate of the resultant ground reaction force, which increased between 4 % and 18 % between movement types. After 15 min of sports-specific use of the tape, the alterations induced by TF remained for some biomechanical risk factors while they became closer to BF again for others, indicating a differential response to prolonged use of taping for different biomechanical variables. ConclusionsAnkle taping protects the ankle joint by reducing biomechanical risk factors associated with ankle sprains and most biomechanical risk factors for ACL or running overuse injuries are not increased. Further research is needed to explore the duration of protective effects, variations across different sports, and its impact on patients with chronic ankle instability, contributing to a more comprehensive understanding of ankle taping's influence on lower extremity biomechanics.

Glycyrrhizic acid ameliorates hepatic fibrosis by inhibiting oxidative stress via AKR7A2

BackgroundHepatic fibrosis is a reversible pathological phenomenon caused by the abnormal proliferation of connective tissues in the liver for self-repair after persistent liver injury. Among these tissues, the activation status of hepatic stellate cells (HSCs) is crucial. Glycyrrhizic acid (GA) agents have been proven to have excellent anti-fibrosis effects, but their targets are unclear. PurposeTo investigate the anti-hepatic fibrosis effect of GA and its target in activated HSCs. MethodsA mouse model of hepatic fibrosis was prepared with 20% carbon tetrachloride (CCl4) and GA was administered continuously for 4 weeks. Subsequently, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), type Ⅲ procollagen peptide (P III P), laminin (LN), hyaluronic acid (HA), and type Ⅳ collagen (Col Ⅳ) were measured. Liver tissues were subjected to hematoxylin and eosin (HE), Masson, and Sirius red staining and proteome sequencing analysis. Based on LX-2 cells, activity-based protein profiling (ABPP) was used to investigate the potential targets of GA, which was further validated by the cellular thermal shift assay (CETSA), immunofluorescence co-localization, molecular docking, small interfering RNA (siRNA) and western blot (WB) assays. ResultsIn vivo, GA significantly reduced serum ALT, AST, HA, P III P, Col IV, and LN levels. HE, Masson, and Sirius red staining showed that GA significantly ameliorated hepatic inflammatory response and collagen deposition in CCl4-treated mice. Proteome sequencing results showed that GA mainly regulated glutathione S-transferase family members involved in glutathione metabolism. In vitro, GA significantly inhibited LX-2 cell proliferation and reduced reactive oxygen species accumulation. ABPP suggested that aldo-keto reductase family 7 member A2 (AKR7A2) was the major binding protein of GA in LX-2 cells. CETSA, fluorescence co-localization, molecular docking, and surface plasmon resonance further validated GA binding to AKR7A2. The WB results showed that GA up-regulated AKR7A2 expression both in vitro and in vivo and was corroborated by siRNA experiments. ConclusionGA targeted AKR7A2 in LX-2 cells to defend against sustained oxidative stress injury, thereby inhibiting the proliferation of activated HSCs and reversing hepatic fibrosis.

HGF ameliorates cardiomyocyte apoptosis and inflammatory response in sepsis via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway

ObjectiveThis study aimed to analyze the impact of HGF on cardiomyocyte injury, apoptosis, and inflammatory response induced by lipopolysaccharide (LPS). MethodsEnzyme-linked immunosorbent assay (ELISA) was utilized to quantify the levels of HGF, interleukin (IL)-6, IL-10, creatine phosphokinase-isoenzyme-MB (CK-MB), and cardiac troponin I (cTnI) in the samples. qPCR and Western blotting (WB) were employed to assess the mRNA and protein expressions of HGF, IL-10, IL-6, PI3K, AKT, p-PI3K, and p-AKT. ResultsThe outcomes of the in vivo experiment revealed that serum levels of IL-6, IL-10, HGF and SOFA scores in the SC group were elevated in contrast to the non-SC group. The correlation analysis indicated a substantial and positive association among serum HGF, IL-6, and IL-10 levels and SOFA scores. Relative to IL-6, IL-10 levels, and SOFA scores, serum HGF demonstrated the highest diagnostic value for SC. Following LPS administration to stimulate H9c2 cells across various periods (0, 12, 24, 48, and 72 h), the levels of myocardial injury markers (CK-MB and cTnI) in the cell supernatants, intracellular inflammatory factors (mRNA and protein levels of IL-10 and IL-6), apoptosis and ROS levels, exhibited a gradual increase followed by a subsequent decline. Following the overexpression of HGF, there was an increase in cell viability, and a decrease in apoptosis, inflammation, oxidative stress injuries, and the protein phosphorylation expressions of PI3K and AKT. After knockdown of HGF expression, the activity of LPS-induced H9c2 cells was further reduced, leading to increased cell injury, apoptosis, inflammation, oxidative stress,and the expression levels of PI3K and Akt protein phosphorylation were further elevated. ConclusionHGF was associated with decreased LPS-induced H9c2 apoptosis and inflammation in H9c2 cells, alongside an improvement in cell viability, indicating potential cytoprotective effects. The mechanism underlying these impacts may be ascribed to the suppression of the PI3K/AKT signaling pathway.

Mechanisms of oxidative stress in myocardial ischemia-reperfusion injury and protective effects of traditional Chinese medicines

Myocardial ischemia is a disease characterized by high morbidity and mortality rates, restoring blood supply to the ischemic area through reperfusion is an effective intervention method. However, numerous studies have shown that reperfusion may cause severe myocardial damage, resulting in myocardial systolic and diastolic dysfunction and seriously affecting myocardial function. This phenomenon is called myocardial ischemia reperfusion injury(MIRI). The physiological and pathological mechanisms of MIRI include oxidative stress, calcium overload, autophagy, pyrolysis, endoplasmic reticulum stress, apoptosis, etc. Oxidative stress plays an important role in MIRI-related cell death and is considered to be the main mechanism of MIRI. The occurrence of oxidative stress is mainly due to the excessive production of reactive oxygen species(ROS), which disrupts the balance of the redox system of the body or tissue. A large number of highly reactive ROS exceed the antioxidant defense capacity of cardiomyocytes, causing modifications in biological macromolecules such as DNA and proteins and resulting in severe reactions like DNA damage, protein dysfunction, cell damage or death, and local inflammation. Oxidative stress mediates apoptosis, autophagy, and inflammatory injury through various pathways, resulting in irreversible cardiomyocyte injury and myocardial dysfunction, which brings significant challenges for clinical treatment and prognosis. In recent years, remarkable progress has been made in understanding oxidative stress in ischemia reperfusion(I/R) injury of different organs and tissue. However, the injury mechanism caused by oxidative stress in restoring blood supply to the ischemic area and the protective effect of TCM remain largely unexplored. This article reviewed the role of oxidative stress in MIRI, the main production pathways of ROS, and the protective effects of TCM on oxidative stress injury during ischemic myocardial reperfusion, so as to provide a reference for future research and clinical treatment in this field.

Effectiveness of Injection of Ginkgo biloba Leaf Extract Combined with Early Rehabilitation on Functional Recovery in Patients Following Ischemic Stroke

The interest in the development of traditional Chinese medicine for the treatment of ischemic stroke (IS) is growing. In this study, we aim to examine the therapeutic effects of the standardized extract of Ginkgo biloba leaf EGb-761 on neurological behavioral outcomes and brain infarction in rats following cerebral ischemia. Additionally, we evaluated the effectiveness of combining EGb-761 injection with early rehabilitation in improving the functional status of patients with IS. The rats were induced with focal transient cerebral ischemia by means of middle cerebral artery occlusion (MCAO). The rats undergoing MCAO/reperfusion were given an intraperitoneal injection of different doses of EGb-761. A total of 65 patients with IS were recruited and assigned into receiving conventional treatments and intravenous drips of Ginaton injection, followed by early rehabilitation. The results showed that neurological deficit scores, brain infarct volume, neuronal apoptosis, and oxidative stress injury were reduced in the MCAO/reperfusion rats treated with different doses of EGb-761 compared to those without EGb-761 treatment. These reductions were more significant in the high-dose EGb-761 treatment group (P &lt;0.05). Both EGb-761 treatment and conventional treatment combined with early rehabilitation resulted in increased muscle strength and higher total BI scores in the patients. However, these increases were more pronounced in the group receiving Ginaton injection (P &lt;0.05). In conclusion, our study demonstrates that acute administration of EGb-761 may contribute to better neurological behavioral outcomes and reduced area of brain infarction in rats following cerebral ischemia and EGb-761 treatment integrated with early rehabilitation could improve the muscle strength and functional recovery of patients with IS.

Chronic cold stress promotes inflammation and ER stress via inhibiting GLP-1R signaling, and exacerbates the risk of ferroptosis in the liver and pancreas

The cold climates in autumn and winter threatens human health. The aim of this study was to reveal the effects of prolonged cold exposure on the liver and pancreas based on GLP-1R signaling, oxidative stress, endoplasmic reticulum (ER) stress and ferroptosis by Yorkshire pig models. Yorkshire pigs were divided into the control group and chronic cold stress (CCS) group. The results showed that CCS induced oxidative stress injury, activated Nrf2 pathway and inhibited the expression of GLP-1R in the liver and pancreas (P<0.05). The toll-like receptor 4 (TLR4) pathway was activated in the liver and pancreas, accompanied by the enrichment of IL-1β and TNF-α during CCS (P<0.05). Moreover, the kinase RNA-like endoplasmic reticulum kinase (PERK), inositol requiring kinase 1 (IRE1), X-box-binding protein 1 (XBP1) and eukaryotic initiation factor 2α (eIF2α) expression in the liver and pancreas was up-regulated during CCS (P<0.05). In addition, CCS promoted the prostaglandin-endoperoxide synthase 2 (PTGS2) expression and inhibited the ferritin H (FtH) expression in the liver. Summarily, CCS promotes inflammation, ER stress and apoptosis by inhibiting the GLP-1R signaling and inducing oxidative stress, and exacerbates the risk of ferroptosis in the liver and pancreas.

Quercetin Solid Lipid Microparticle Stability and Deposition in Rat Lungs: A Study of Surfactant Effect

This study aims to determine the effect of surfactant concentration on Quercetin SLM as a potential carrier of respiratory diseases, especially ones resulting from oxidative stress injury. Quercetin is a natural antioxidant with high activity. SLM was formed with 5% compritol 888 ATO as a lipid and different concentrations of poloxamer 188 as a surfactant. SLM was produced by a combination of emulsification and sonication involving freeze drying. SLM is characterized by organolepsis, morphology, yield, particle size, drug loading, and entrapment efficiency. The antioxidant activity of quercetin SLMs was tested using the ABTS method. SLMs are characterized as having round and smooth morphology, high yield (F1 88.53%; F2 91.44%; F3 92.87%); particle size (F1 1.81 um; F2 1.90 um; F3 1.94 um); high drug loading (F1 15.96%; F2 13.74%; F3 13.19%); and high entrapment efficiency (F1 96.53%; F2 87.94%; F3 87.48%). Increasing surfactant concentration did not produce a significant difference between formulas. Quercetin SLM showed high antioxidant activity (Quercetin 94.43%; F1 94.35%; F2 94.36%; F3 94.37%). SLM was stable at storage temperatures between 25°C and 40°C. The effect of surfactant can be seen on particle size, drug loading, and entrapment efficiency at 40°C. Results of in vivo deposition study indicated that all SLM formulas were able to deliver quercetin to the lungs. Increasing the concentration of surfactant in Quercetin SLMs made no difference to the lung deposition as confirmed by observations conducted at 1 hour and 4 hours. Quercetin SLM has the potential for lung delivery by inhalation.

The Role of the Nrf2 Pathway in Airway Tissue Damage Due to Viral Respiratory Infections.

Respiratory viruses constitute a significant cause of illness and death worldwide. Respiratory virus-associated injuries include oxidative stress, ferroptosis, inflammation, pyroptosis, apoptosis, fibrosis, autoimmunity, and vascular injury. Several studies have demonstrated the involvement of the nuclear factor erythroid 2-related factor 2 (Nrf2) in the pathophysiology of viral infection and associated complications. It has thus emerged as a pivotal player in cellular defense mechanisms against such damage. Here, we discuss the impact of Nrf2 activation on airway injuries induced by respiratory viruses, including viruses, coronaviruses, rhinoviruses, and respiratory syncytial viruses. The inhibition or deregulation of Nrf2 pathway activation induces airway tissue damage in the presence of viral respiratory infections. In contrast, Nrf2 pathway activation demonstrates protection against tissue and organ injuries. Clinical trials involving Nrf2 agonists are needed to define the effect of Nrf2 therapeutics on airway tissues and organs damaged by viral respiratory infections.

Update on Rehabilitation Strategies for Swimmers' Shoulder: A Narrative Review

AbstractSwimmers' shoulder is one of the common overuse injuries having multifactorial causes with a gradual onset. Swimmers' experience pain in the pull-through phase, during the mid-stroke wherein the arm is maximally internally rotated and adducted. This occurs due to a significant amount of force generated by the pectorals, latissimus dorsi, subscapularis, serratus anterior, rhomboids, and supraspinatus for this movement. The repetitive use of shoulder muscles during the swim strokes predisposes it to overuse injuries among which shoulder impingement is common. It hinders participation of athletes in competitive events and reduces the efficiency of the swim performance. This review aims to provide a consolidated overview and identify various rehabilitation strategies and exercise programs for swimmers' shoulder. A thorough search was done on PubMed, ScienceDirect, Web of Science, Cochrane, CINAHL, and Clinical Key to find relevant articles in relation to the rehabilitation strategies available for swimmers' shoulder. Overall, this review suggests that aquatic concentric-eccentric exercise, Kinesio taping, land-based strengthening exercises, and rhythmic stabilization exercises significantly improve pain and functional activity in individuals with swimmers' shoulder.

M6A demethylase FTO-stabilized exosomal circBRCA1 alleviates oxidative stress-induced granulosa cell damage via the miR-642a-5p/FOXO1 axis

BackgroundPremature ovarian insufficiency (POI) is an important cause of female infertility and seriously impacts the physical and psychological health of patients. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exs, H-Exs) have exhibited protective effects on ovarian function with unclear mechanisms.MethodsA comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify POI-associated circRNAs and miRNAs. The relationship between HucMSC-derived exosomal circBRCA1/miR-642a-5p/FOXO1 axis and POI was examined by RT-qPCR, Western blotting, reactive oxygen species (ROS) staining, senescence-associated β-gal (SA-β-gal) staining, JC-1 staining, TEM, oxygen consumption rate (OCR) measurements and ATP assay in vivo and in vitro. RT-qPCR detected the expression of circBRCA1 in GCs and serum of patients with normal ovarian reserve function (n = 50) and patients with POI (n = 50); then, the correlation of circBRCA1 with ovarian reserve function indexes was analyzed.ResultsHerein, we found that circBRCA1 was decreased in the serum and ovarian granulosa cells (GCs) of patients with POI and was associated with decreased ovarian reserve. H-Exs improved the disorder of the estrous cycles and reproductive hormone levels, reduced the number of atretic follicles, and alleviated the apoptosis and senescence of GCs in rats with POI. Moreover, H-Exs mitigated mitochondrial damage and reversed the reduced circBRCA1 expression induced by oxidative stress in GCs. Mechanistically, FTO served as an eraser to increase the stability and expression of circBRCA1 by mediating the m6A demethylation of circBRCA1, and exosomal circBRCA1 sponged miR-642a-5p to block its interaction with FOXO1. CircBRCA1 insufficiency aggravated mitochondrial dysfunction, mimicking FTO or FOXO1 depletion effects, which was counteracted by miR-642a-5p inhibition.ConclusionH-Exs secreted circBRCA1 regulated by m6A modification, directly sponged miR-642a-5p to upregulate FOXO1, resisted oxidative stress injuries in GCs and protected ovarian function in rats with POI. Exosomal circBRCA1 supplementation may be a general prospect for the prevention and treatment of POI.Graphical

Mitochondria fission accentuates oxidative stress in hyperglycemia-induced H9c2 cardiomyoblasts in vitro by regulating fatty acid oxidation.

Oxidative stress plays a pivotal role in the development of diabetic cardiomyopathy (DCM). Previous studies have revealed that inhibition of mitochondrial fission suppressed oxidative stress and alleviated mitochondrial dysfunction and cardiac dysfunction in diabetic mice. However, no research has confirmed whether mitochondria fission accentuates hyperglycemia-induced cardiomyoblast oxidative stress through regulating fatty acid oxidation (FAO). We used H9c2 cardiomyoblasts exposed to high glucose (HG) 33 mM to simulate DCM in vitro. Excessive mitochondrial fission, poor cell viability, and lipid accumulation were observed in hyperglycemia-induced H9c2 cardiomyoblasts. Also, the cells were led to oxidative stress injury, lower adenosine triphosphate (ATP) levels, and apoptosis. Dynamin-related protein 1 (Drp1) short interfering RNA(siRNA) decreased targeted marker expression, inhibited mitochondrial fragmentation and lipid accumulation, suppressed oxidative stress, reduced cardiomyoblast apoptosis, and improved cell viability and ATP levels in HG-exposed H9c2 cardiomyoblasts, but not in carnitine palmitoyltransferase 1 (CPT1) inhibitor etomoxir treatment cells. We also found subcellular localization of CPT1 on the mitochondrial membrane, FAO, and levels of nicotinamide adenine dinucleotide phosphate(NADPH) were suppressed after exposure to HG treatment, whereas Drp1 siRNA normalized mitochondrial CPT1, FAO, and NADPH. However, the blockade of FAO with etomoxir abolished the above effects of Drp1 siRNA in hyperglycemia-induced H9c2 cardiomyoblasts. The preservation of mitochondrial function through the Drp1/CPT1/FAO pathway is the potential mechanism of inhibited mitochondria fission in attenuating oxidative stress injury of hyperglycemia-induced H9c2 cardiomyoblasts.