Curcumin alleviates heatstroke-induced liver injury in dry-heat environments by inhibiting the expression of NF-κB, iNOS, and ICAM-1 in rats.

we aimed to monitor liver injury in rat model during heat stress and heatstroke in dry-heat environment and investigate the effects of curcumin on heatstroke-induced liver injury and the underlying mechanisms. Sprague-Dawley (SD) rats were randomly divided into four groups: normal saline (NS), and 50 (50-cur), 100 (100-cur), and 200 mg/kg curcumin (200-cur) groups. They were administered the indicated doses of curcumin by gavage once daily for 7 days. On day 8, the rats were transferred to a simulated climate cabin, At 0, 50, 100, and 150 min, the core temperature (Tc) was measured respectively. After sacrificing the rats, tissue samples were collected, measure histology indices, serum enzymes, lipopolysaccharides (LPSs), cytokines, nuclear factor-kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and intercellular adhesion molecule-1 (ICAM-1). The Tc increased with time in all groups. Curcumin alleviation of symptoms and improvement in pathological scores. The level of enzymes, LPS, and cytokines increased during heatstroke in the NS group, but curcumin decreased the levels of these indicators. The differences of the indicators between NS and 200-cur groups at 150 min were significant (P < 0.05). The expression of NF-κB p65, iNOS, and ICAM-1 was upregulated in the NS group at 150 min, but their expression was relatively lower in the curcumin groups (P < 0.05). Thus, our findings indicate acute liver injury during heat stress and heatstroke. The mechanism involves cascade-amplification inflammatory response induced by the gut endotoxin. Furthermore, curcumin alleviated heatstroke-induced liver injury in a dose-dependent manner by downregulating NF-κB, iNOS, and ICAM-1.

Altered static brain activity and functional connectivity after heat stroke.

This study aimed to investigate the alteration of brain function based on resting-state functional MRI in patients after heat stroke. This study included 10 cases of patients after heat stroke and 10 cases of healthy controls. Abnormal brain function was calculated using amplitude of low-frequency fluctuations (ALFF) and degree centrality analysis, as well as functional connectivity analysis based on regions of interest (ROI). Correlation analyses were performed to evaluate the association between brain function changes and clinical scales. Combining ALFF and degree centrality results, the decreased brain regions included the left cuneus and the right angular gyrus, while the increased brain regions included the right cerebellar_Crus1. Using the left cuneus with significant differences in ALFF and degree centrality as ROI, the functional connectivity results revealed decreased brain regions including bilateral lingual gyrus, bilateral postcentral cingulate gyrus, and left precentral gyrus. The degree centrality value of the right cerebellar_Crus1 was positively correlated with glasgow coma scale (GCS) scores ( r  = 0.726, P  = 0.027), and the functional connectivity value of the right posterior cingulate gyrus was positively correlated with GCS scores ( r  = 0.717, P  = 0.030). Heat stroke patients exhibit abnormal activity in multiple brain regions, which has important clinical significance for evaluating the severity of the disease.

[Four cases of occupational heatstroke among sanitation workers working in high temperature weather].

Through the report of 4 cases of occupational heatstroke among sanitation workers working in high-temperature weather, this study analyzes the risk of occupational heatstroke among workers in the environmental sanitation industry working in high-temperature weather, and provides scientific suggestions for standardizing occupational health management, safeguarding the health rights and interests of workers, and preventing the occurrence of occupational heatstroke in summer. Through case analysis, we aim to raise high awareness of the occupational health of sanitation workers in the whole society, in order to provide a scientific and healthy working environment for sanitation workers and promote their physical and mental health.

Quality assessment of heatstroke videos on TikTok.

Background: The prevalence of heatstroke is rising due to global warming, making it a serious but preventable condition, highlighting the urgent need for effective dissemination of relevant health education to the general public. Advances in technology have made accessing health information more convenient and rapid. In recent years, short videos have become a primary medium for delivering health education, with TikTok gaining considerable popularity among the general public. However, the quality of heatstroke-related health education content on TikTok deserves closer scrutiny. Objective: This study aimed to evaluate the quality and content of heatstroke-related videos available on TikTok. Methods: The present study analyzed the top 100 heatstroke-related short videos on TikTok, focusing on their characteristics, quality, and the content they conveyed. The quality of these videos was assessed using the DISCERN instrument. In addition, the completeness of the videos was assessed by examining six key aspects: disease definition, clinical manifestations, risk factors, assessment, management, and outcomes. Results: The study included a total of 90 videos. The results showed that news organizations and healthcare professionals were the primary contributors to these videos, with those from news organizations receiving the most attention. In contrast, those from healthcare professionals received comparatively less engagement. Overall, the quality of the information was found to be moderately low, with the highest quality videos posted by non-profit organizations, followed by those posted by healthcare professionals. The majority of videos uploaded described the disease definition, clinical presentation, risk factors, assessment, management, and outcomes of heatstroke. Conclusion: The quality of information provided in heatstroke-related short videos on TikTok is generally inadequate and requires significant improvement. In addition, such content should be subject to government review to ensure its accuracy and reliability.

Approach to heat-related illness.

OBJECTIVE: To describe heat-related illness and provide approaches for treatment in family practice. SOURCES OF INFORMATION: The MeSH terms heat-related illness and primary care were searched in PubMed. Clinical trials, practice reviews, and systematic reviews were included in this review. Reference lists were reviewed for additional articles. MAIN MESSAGE: Extreme heat events are increasing in frequency due to climate change and can directly result in heat exhaustion, heat stroke, or death. Exposure to extreme heat also exacerbates underlying health conditions. Patients may be at increased risk of heat-related illness because of underlying sensitivity to heat, increased exposure to heat, or barriers to resources. CONCLUSION: Family physicians can help prevent heat-related illness by identifying and counselling patients who are at increased risk and by advocating for interventions that reduce the chance of heat-related illness.

Curcumin nanoparticles in heat stroke management.

OBJECTIVE: The exacerbation of extreme high-temperature events due to global climate change poses a significant challenge to public health, particularly impacting the central nervous system through heat stroke. This study aims to develop Poly(amidoamine) (PAMAM) nanoparticles loaded with curcumin (PAMAM@Cur) to enhance its therapeutic efficacy in hypothalamic neural damage in a heat stroke model and explore its potential mechanisms. METHODS: Curcumin (Cur) was encapsulated into PAMAM nanoparticles through a hydrophobic interaction method, and various techniques were employed to characterize their physicochemical properties. A heat stroke mouse model was established to monitor body temperature and serum biochemical parameters, conduct behavioral assessments, histological examinations, and biochemical analyses. Transcriptomic and proteomic analyses were performed to investigate the therapeutic mechanisms of PAMAM@Cur, validated in an N2a cell model. RESULTS: PAMAM@Cur demonstrated good stability, photostability, cell compatibility, significant blood-brain barrier (BBB) penetration capability, and effective accumulation in the brain. PAMAM@Cur markedly improved behavioral performance and neural cell structural integrity in heat stroke mice, alleviated inflammatory responses, with superior therapeutic effects compared to Cur or PAMAM alone. Multi-omics analysis revealed that PAMAM@Cur regulated antioxidant defense genes and iron death-related genes, particularly upregulating the PCBP2 protein, stabilizing SLC7A11 and GPX4 mRNA, and reducing iron-dependent cell death. CONCLUSION: By enhancing the drug delivery properties of Cur and modulating molecular pathways relevant to disease treatment, PAMAM@Cur significantly enhances the therapeutic effects against hypothalamic neural damage induced by heat stroke, showcasing the potential of nanotechnology in improving traditional drug efficacy and providing new strategies for future clinical applications. SIGNIFICANCE: This study highlights the outlook of nanotechnology in treating neurological disorders caused by heat stroke, offering a novel therapeutic approach with potential clinical applications.

Effect of platelet dynamic changes on disseminated intravascular coagulation and prognosis in severe heatstroke patients.

OBJECTIVE: This study aimed to investigate the dynamic changes in the platelets of patients with severe heatstroke and the impact of these changes on the occurrence of disseminated intravascular coagulation (DIC) and prognosis in them. METHODS: This retrospective cohort study conducted at two tertiary hospitals recruited 264 patients with severe heatstroke. Logistic regression was used to analyze the association between platelet counts and DIC. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of platelets count for DIC occurrence. We used mediation effect to analysis the role of DIC as a mediating variable to mediate the relationship between platelet count decrease after 24 hours and death. RESULTS: There were 214 patients with lower platelet counts compared to admission (107 × 109/L[69,168] vs.171 × 109/L[126,215], p < 0.001). The DIC patients had lower platelet counts than the non-DIC patients when measured in the emergency department and after 24 hours. The platelet count decrease after 24 hours was a risk factor for DIC (odds ratio [OR] = 2.710, 95% confidence interval [CI] = 1.069-6.869). The results of the ROC curve revealed that the predictive performance of the platelet count after 24 hours (area under the curve [AUC] = 0.8685, 95% CI = 0.8173-0.9197) was significantly better than that of the platelet count measured in the emergency department (AUC = 0.7080, 95% CI = 0.6345-0.7815). Mediation analyses showed that PLT decrease after 24 hours did not directly lead to death, but can indirectly cause death by inducing the development of DIC. CONCLUSIONS: Decreased platelet count is an independent risk factor for DIC in patients with severe heatstroke. Although the platelet counts measured in the emergency department and after 24 hours show a good predictive performance for DIC occurrence, the prediction performance of the latter is better.

APTT and D-dimer as biomarkers for heatstroke in patients with severe heat-related illnesses.

The objective of this study was to analyze the changes of activated partial thromboplastin time (APTT) and D-dimer in severe heatstroke (HS) patients and their value in identifying HS patients and to analyze clinical features and early laboratory test results of heat-related illnesses. Forty-five patients with heat-related illnesses who were admitted to the Department of Emergency and Intensive Care Medicine of Suining Central Hospital from June 2022 to April 2023 were retrospectively analyzed. Patients were divided into 3 groups based on their clinical diagnosis: classic HS group, exertional HS group, and control group. General date and laboratory test results were collected, especially APTT and D-dimer. The receiver operating characteristic curve was used to analyze D-dimer and APTT. : There were differences in gender distribution among the 3 groups. Exertional HS was dominated by male patients, and classic HS was dominated by elderly patients. Binary logistic regression analysis of coagulation index showed a significant correlation between D-dimer and APTT and HS. The receiver operating characteristic curve results showed that APTT and D-dimer had high sensitivity and specificity in the identification of HS with an area under the curve (AUC) of 0.846, sensitivity of 97%, and specificity of 58.3% for APTT and an AUC of 0.861, sensitivity of 72%, and specificity of 91.7% for D-dimer (D-dimer + APTT [AUC, 0.929; sensitivity, 81.8%-91.7%; P < .001]). : The mortality rate of HS is high, and early diagnosis is particularly important. APTT and D-dimer may be used as markers assisting in identifying HS.

Case discussion: The effect of extreme temperatures on an older adult.

Climate change can cause high temperatures that can affect the older adult in significant ways. Older adults may not be aware of the dangers of high temperature days and may continue with old habits such as staying in the sun to garden without sunscreen or a hat as they may have done in years past. High temperatures can cause impairment of the tone and structure of blood vessels by interfering with nitric oxide synthesis and cytokine production and can cause systemic inflammation, all of which significantly contribute to dehydration in older adults, who are known to have a decreased sense of thirst, resulting in increased blood viscosity and the risk of heat induced shock and thrombotic strokes. This case discussion highlights the effects of high temperatures due to climate change on an older adult, and what nurse practitioners need to be aware of when assessing older adults who may be suffering from heat exhaustion or heat stroke, and how to manage appropriately.

Machine learning-based analysis and prediction of meteorological factors and urban heatstroke diseases.

Introduction: Heatstroke is a serious clinical condition caused by exposure to high temperature and high humidity environment, which leads to a rapid increase of the core temperature of the body to more than 40°C, accompanied by skin burning, consciousness disorders and other organ system damage. This study aims to analyze the effect of meteorological factors on the incidence of heatstroke using machine learning, and to construct a heatstroke forecasting model to provide reference for heatstroke prevention. Methods: The data of heatstroke incidence and meteorological factors in a city in South China from May to September 2014-2019 were analyzed in this study. The lagged effect of meteorological factors on heatstroke incidence was analyzed based on the distributed lag non-linear model, and the prediction model was constructed by using regression decision tree, random forest, gradient boosting trees, linear SVRs, LSTMs, and ARIMA algorithm. Results: The cumulative lagged effect found that heat index, dew-point temperature, daily maximum temperature and relative humidity had the greatest influence on heatstroke. When the heat index, dew-point temperature, and daily maximum temperature exceeded certain thresholds, the risk of heatstroke was significantly increased on the same day and within the following 5 days. The lagged effect of relative humidity on the occurrence of heatstroke was different with the change of relative humidity, and both excessively high and low environmental humidity levels exhibited a longer lagged effect on the occurrence of heatstroke. With regard to the prediction model, random forest model had the best performance of 5.28 on RMSE and dropped to 3.77 after being adjusted. Discussion: The incidence of heatstroke in this city is significantly correlated with heat index, heatwave, dew-point temperature, air temperature and zhongfu, among which the heat index and dew-point temperature have a significant lagged effect on heatstroke incidence. Relevant departments need to closely monitor the data of the correlated factors, and adopt heat prevention measures before the temperature peaks, calling on citizens to reduce outdoor activities.

Protection of Parkin over-expression on lung in rats with exertional heat stroke by activating mitophagy.

OBJECTIVE: To investigate the role of Parkin overexpression-induecd mitophagy in alleviating acute lung injury of exertional heat stroke(EHS) rats. METHODS: Eighty SD rats were divided into four groups: Control group (CON group), Control Parkin overexpression group (CON + Parkin group), exertional heat stroke group (EHS group), and exertional heat stroke Parkin overexpression group (EHS + Parkin group). Adeno-associated virus carrying the Parkin gene was intravenously injected into the rats to overexpress Parkin in the lung tissue. An exertional heat stroke rat model was established, and survival curves were plotted. Lung Micro-CT was performed, and lung coefficient and pulmonary microvascular permeability were measured. Enzyme-linked immunosorbent assays(ELISA) were used to determine the levels of interleukin-6(IL-6), interleukin-1ß(IL-1ß), Tumor necrosis factor-α(TNF-α), and reactive oxygen species(ROS). The morphology of mitochondria in type II epithelial cells of lung tissue was observed using transmission electron microscopy. The apoptosis of lung tissue, the level of mitophagy, and the co-localization of Pink1 and Parkin were determined using immunofluorescence. The expression of Pink1, Parkin, MFN2, PTEN-L, PTEN, p62, and microtubule associated protein 1 light chain 3 (LC3) in rat lung tissue was measured by western blot. RESULTS: Compared with the CON group, there were more severe lung injury and more higher levels of IL-6, IL-1ß, TNF-α in EHS rats. Both of the LC3-II/LC3-I ratio and the co-localization of LC3 and Tom20 in the lung tissue of EHS rats decreased. Compared with the EHS group, the survival rate of rats in the EHS + Parkin overexpression group was significantly increased, lung coefficient and pulmonary microvascular permeability were reduced, and pathological changes such as exudation and consolidation were significantly alleviated. The levels of IL-6, IL-1ß, TNF-α, and ROS were significantly decreased; the degree of mitochondrial swelling in type II alveolar epithelial cells was reduced, and no vacuolization was observed. Lung tissue apoptosis was reduced, and the colocalization fluorescence of Pink1 and Parkin, as well as LC3 and Tom20, were increased. The expression of Parkin and LC3-II/LC3-I ratio in lung tissue were both increased, while the expression of P62, Pink1, MFN2, and PTEN-L was decreased. CONCLUSION: Pink1/Parkin-mediated mitophagy dysfunction is one of the mechanisms underlying acute lung injury in rats with EHS, and activation of Parkin overexpression induced-mitophagy can alleviate acute lung injury caused by EHS.

Exertional Heat Stroke Best Practices in U.S. Emergency Medical Services Guidelines.

BACKGROUND: Exertional heat illnesses (EHIs), specifically exertional heat stroke (EHS), are a top cause of nonaccidental death among U.S. laborers. EHS management requires coordination between Emergency Medical Services (EMS) and workplace officials to implement cold water immersion (CWI) and cool first, transport second (CFTS). OBJECTIVE: The purpose of this article was to quantify and identify existing statewide EMS guidelines, determine whether statewide EHS guidelines improved outcomes for EHIs in laborers, and examine the odds of laborer EHS fatalities when best practices are present in EMS statewide guidelines. METHODS: The Paramedic Protocol Provider database and official EMS websites were examined to determine which U.S. states had statewide EMS guidelines and, for those with statewide guidelines, a two-way χ2 analysis with associated odds ratios examined EHI outcomes. Statewide EMS guidelines underwent content analysis by three independent reviewers regarding EHS best practices. Significance was set a priori at p < 0.05. RESULTS: Among 50 states, the District of Columbia, and Puerto Rico, 57.7% (n = 30) had statewide EMS guidelines and 42.3% (n = 22) did not. There was a significant association for EHI outcome for states recommending CWI as a cooling method vs. those that did not (χ21 = 3.336; p = 0.049). The odds of EHS deaths for laborers were 3.0 times higher if CWI was not included in the EMS guidelines. There was a significant association in EHI outcomes for states without CFTS (χ21 = 5.051; p = 0.017). The odds of laborers dying from EHS were 3.7 times higher in states without CFTS. CONCLUSIONS: Laborers are 3.0 and 3.7 times less likely to die from EHS when statewide EMS guidelines include CWI and CFTS, respectively.

HMGB1 released from pyroptotic vascular endothelial cells promotes immune disorders in exertional heatstroke.

BACKGROUND AND OBJECTIVE: Exertional heatstroke (EHS) mainly occurs in healthy young people with rapid onset and high mortality. EHS immune disorders can cause systemic inflammatory responses and multiple organ failure; however, the underlying mechanisms remain unclear. As high mobility group box 1 (HMGB1) is a prototypical alarmin that activates inflammatory and immune responses, this study aimed to investigate the effect and mechanism of HMGB1 in the pathogenesis of EHS. METHODS: Peripheral blood mononuclear cell (PBMC) transcriptome sequencing of healthy volunteers, classical heatstroke patients, and EHS patients was performed. A mouse model of EHS was established and murine tissue damage was evaluated by H&E staining. HMGB1 localization and release were visualized using immunofluorescence staining. Human umbilical vein endothelial cells (HUVECs) and THP-1 cells were co-cultured to study the effects of HMGB1 on macrophages. A neutralizing anti-HMGB1 antibody was used to evaluate the efficacy of EHS treatment in mice. RESULTS: Plasma and serum HMGB1 levels were significantly increased in EHS patients or mice. EHS-induced endothelial cell pyroptosis promoted HMGB1 release in mice. HMGB1 derived from endothelial cell pyroptosis enhanced macrophage pyroptosis, resulting in immune disorders under EHS conditions. Administration of anti-HMGB1 markedly alleviated tissue injury and systemic inflammatory responses after EHS. CONCLUSIONS: The release of HMGB1 from pyroptotic endothelial cells after EHS promotes pyroptosis of macrophages and systemic inflammatory response, and HMGB1-neutralizing antibody therapy has good application prospects for EHS.

Hyperbaric oxygen therapy attenuates heatstroke-induced hippocampal injury by inhibiting microglial pyroptosis.

Background: Central nervous system (CNS) injury is the most prominent feature of heatstroke and the hippocampus is prone to damage. However, the mechanisms underlying the heatstroke-induced hippocampal injury remain unclear. Hyperbaric oxygen (HBO) therapy prevents CNS injury in heatstroke mice. However, the underlying mechanisms of HBO in heatstroke-induced hippocampal injury remain unclear. This study aimed to elucidate the protective effects of HBO against hippocampal injury and its potential role in microglial pyroptosis in heatstroke rats.Methods: A rat heatstroke model and a heat stress model with a mouse microglial cell line (BV2) were, respectively, used to illustrate the effect of HBO on heat-induced microglial pyroptosis in vivo and in vitro. We used a combination of molecular and histological methods to assess microglial pyroptosis and neuroinflammation both in vivo and in vitro.Results: The results revealed that HBO improved heatstroke-induced survival outcomes, hippocampal injury, and neurological dysfunction in rats. In addition, HBO mitigates microglial pyroptosis and reduces the expression of pro-inflammatory cytokines in the hippocampus of heatstroke rats. In vitro experiments showed that HBO attenuated BV2 cell injury under heat stress. Furthermore, HBO prevented heat-induced pyroptosis of BV2 cells, and the expression of pro-inflammatory cytokines IL-18 and IL-1ß was reduced. Mechanistically, HBO alleviates heatstroke-induced neuroinflammation and hippocampal injury by preventing microglial pyroptosis. Conclusions: In conclusion, HBO attenuates heatstroke-induced neuroinflammation and hippocampal injury by inhibiting microglial pyroptosis.

Impact of heat waves on human morbidity and hospital admissions in a city of the western mediterranean area.

PURPOSE: The effect of heat waves on mortality is well known, but current evidence on morbidity is limited. Establishing the consequences of these events in terms of morbidity is important to ensure communities and health systems can adapt to them. METHODS: We thus collected data on total daily emergency hospital admissions, admissions to critical care units, emergency department admissions, and emergency admissions for specific diagnoses to Hospital Universitario de Son Espases from 1 January 2005 to 31 December 2021. A heat wave was defined as a period of ≥ 2 days with a maximum temperature ≥ 35 °C, including a 7 day lag effect (inclusive). We used a quasi-Poisson generalized linear model to estimate relative risks (RRs; 95%CI) for heat wave-related hospital admissions. RESULTS: Results showed statistically significant increases in total emergency admissions (RR 1.06; 95%CI 1 - 1.12), emergency department admissions (RR 1.12; 95%CI 1.07 - 1.18), and admissions for ischemic stroke (RR 1.26; 95%CI 1.02 - 1.54), acute kidney injury (RR 1.67; 95%CI 1.16 - 2.35), and heat stroke (RR 18.73, 95%CI 6.48 - 45.83) during heat waves. CONCLUSION: Heat waves increase hospitalization risk, primarily for thromboembolic and renal diseases and heat strokes.

Catalpol alleviates heat stroke-induced liver injury in mice by downregulating the JAK/STAT signaling pathway.

BACKGROUND: Heat stroke (HS) generated liver injury is a lethal emergency that occurs when the body is exposed to temperatures up to 40 °C for a few hours. PURPOSE: This study aimed to evaluate the therapeutic prospects of Catalpol (CA) from the blood-cooling herb Rehamanniae Radix on liver injury by HS. STUDY DESIGN AND METHODS: A murine HS model (41 ± 0.5 °C, 60 ± 5 % relative humidity) and two cell lines (lipopolysaccharide + 42 °C) were used to assess the protective effects of CA on physiological, pathological, and biochemical features in silico, in vivo, and in vitro. RESULTS: CA treatment significantly improved survival rates in vivo and cell viability in vitro over those of the untreated group. Additionally, CA treatment reduced core body temperature, enhanced survival time, and mitigated liver tissue damage. Furthermore, CA treatment also reduced the activities of AST and ALT enzymes in the serum samples of HS mice. Molecular docking analysis of the 28 overlapping targets between HS and CA revealed that CA has strong binding affinities for the top 15 targets. These targets are primarily involved in nine major signaling pathways, with the JAK-STAT pathway being highly associated with the other eight pathways. Our findings also indicate that CA treatment significantly downregulated the expression of proinflammatory cytokines both in vivo and in vitro while upregulating the expression of anti-inflammatory cytokines. Moreover, CA treatment reduced the levels of JAK2, phospho-STAT5, and phospho-STAT3 both in vivo and in vitro, which is consistent with its inhibition of the apoptotic markers p53, Bcl2, and Bax. CONCLUSIONS: Heat stroke-induced liver injury was inhibited by CA through the downregulation of JAK/STAT signaling.

Jiawei Bai-Hu-decoction ameliorated heat stroke-induced brain injury by inhibiting TLR4/NF-κB signal and mitophagy of glial cell.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Bai-Hu-Decoction (JWBHD), a prescription formulated with seven traditional Chinese medicinal material has demonstrated clinical efficacy in mitigating brain injury among heat stroke (HS) patients. AIM OF THE STUDY: This study aimed to evaluate the therapeutic efficacy of JWBHD on rat model of HS and to explore its therapeutic mechanisms by integrating network pharmacology and pharmacodynamic methodologies, which major components were analyzed by using UPLC-MS/MS. MATERIALS AND METHODS: The network pharmacology analysis was firstly conducted to predict the potential active ingredients and therapeutic targets of JWBHD. The anti-HS effectiveness of JWBHD was then evaluated on rats experienced HS. Rat brain tissues were harvested for a comprehensive array of experiments, including Western blot, PCR, H&E staining, Nissl staining, ELISA, transmission electron microscope, flow cytometry and immunofluorescence to validate the protective effects of JWBHD against HS-induced brain damage. Furthermore, the inhibitory effects of JWBHD on TLR4/NF-κB signal and mitophagy of glial were further verified on HS-challenged F98 cell line. Finally, the chemical compositions of the water extract of JWBHD were analyzed by using UPLC-MS/MS. RESULTS: Network pharmacology has identified fifty core targets and numerous HS-related signaling pathways as potential therapeutic targets of JWBHD. Analysis of protein-protein interaction (PPI) and GO suggests that JWBHD may suppress HS-induced inflammatory signals. In experiments conducted on HS-rats, JWBHD significantly reduced the core temperature, restored blood pressure and alleviated neurological defect. Furthermore, JWBHD downregulated the counts of white blood cells and monocytes, decreased the levels of inflammatory cytokines such as IL-1ß, IL-6 and TNF-α in peripheral blood, and suppressed the expression of TLR4 and NF-κB in the cerebral cortex of HS-rats. Besides, JWBHD inhibited the apoptosis of cortical cells and mitigated the damage to the cerebral cortex in HS group. Conversely, overactive mitophagy was observed in the cerebral cortex of HS-rats. However, JWBHD restored the mitochondrial membrane potential and downregulated expressions of mitophagic proteins including Pink1, Parkin, LC3B and Tom20. JWBHD reduced the co-localization of Pink1 and GFAP, a specific marker of astrocytes in the cerebral cortex of HS-rats. In addition, the inhibitory effect of JWBHD on TLR4/NF-κB signaling and overactive mitophagy were further confirmed in F98 cells. Finally, UPLC-MS/MS analysis showed that the main components of JWBHD include isoliquiritigenin, liquiritin, dipotassium glycyrrhizinate, ginsenoside Rb1, ginsenoside Re, etc. CONCLUSIONS: JWBHD protected rats from HS and prevented HS-induced damage in the cerebral cortex by suppressing TLR4/NF-κB signaling and mitophagy of glial.

Heat stress-induced platelet dysfunction is associated with loss of fibrinogen and is improved by fibrinogen supplementation.

INTRODUCTION: Heatstroke is a critical heat-related condition characterized by coagulopathy and multiple organ dysfunction. One of the most severe complications of heatstroke is disseminated intravascular coagulation. This condition manifests as excessive clot formation and bleeding that are primarily due to platelet depletion and dysfunction. Fibrinogen plays a crucial role in hemostasis because it links integrin αIIbß3 on adjacent platelets, thereby promoting the platelet activation and aggregation necessary for clot formation. However, reduced fibrinogen levels may impair the formation of the initial platelet plug and increase the risk of bleeding. The current study explored the effect of fibrinogen on platelet dysfunction in a heatstroke model. MATERIALS AND METHODS: Male Wistar rats were subjected to heat stress, and subsequent changes in hemodynamic, biochemical, and coagulation parameters were analyzed. Platelet viability, aggregation, adhesion, spreading and fibrin clot retraction were assessed. RESULTS: The rats with heatstroke exhibited a variety of clinical symptoms, including hypotension, tachycardia, multiple organ dysfunction, and coagulopathy. Platelet viability in the heatstroke group was comparable to that in the healthy control group. However, the heatstroke group exhibited significant reductions in plasma fibrinogen levels and platelet aggregation, adhesion, spreading, and fibrin clot retraction. Notably, fibrinogen supplementation markedly augmented the aggregation responses of platelets in the heatstroke group. The impairment of platelet adhesion, spreading, and fibrin clot retraction in the rats with heatstroke was partially ameliorated by fibrinogen supplementation. CONCLUSIONS: An early use of fibrinogen replacement may serve as a therapeutic intervention to alleviate platelet hyporeactivity and prevent the complications in patients with heatstroke.