Biased allosteric activation of ketone body receptor HCAR2 suppresses inflammation.

Hydroxycarboxylic acid receptor 2 (HCAR2), modulated by endogenous ketone body ß-hydroxybutyrate and exogenous niacin, is a promising therapeutic target for inflammation-related diseases. HCAR2 mediates distinct pathophysiological events by activating Gi/o protein or ß-arrestin effectors. Here, we characterize compound 9n as a Gi-biased allosteric modulator (BAM) of HCAR2 and exhibit anti-inflammatory efficacy in RAW264.7 macrophages via a specific HCAR2-Gi pathway. Furthermore, four structures of HCAR2-Gi complex bound to orthosteric agonists (niacin or monomethyl fumarate), compound 9n, and niacin together with compound 9n simultaneously reveal a common orthosteric site and a unique allosteric site. Combined with functional studies, we decipher the action framework of biased allosteric modulation of compound 9n on the orthosteric site. Moreover, co-administration of compound 9n with orthosteric agonists could enhance anti-inflammatory effects in the mouse model of colitis. Together, our study provides insight to understand the molecular pharmacology of the BAM and facilitates exploring the therapeutic potential of the BAM with orthosteric drugs.

Outcomes after pancreaticoduodenectomy with or without preoperative hyperbaric oxygen therapy.

Background: Hyperbaric oxygen (HBO2) therapy is an alternative method against the deleterious effects of ischemic/reperfusion (I/R) injury and its inflammatory response. This study assessed the effect of preoperative HBO2 on patients undergoing pancreaticoduodenectomy. Study Design: Patients were randomized via a computer-generated algorithm. Patients in the HBO2 cohort received two sessions of HBO2 the evening before and the morning of surgery. Measurements of inflammatory mediators and self-assessed pain scales were determined pre-and postoperatively. In addition, perioperative variables and long-term survival were collected and analyzed. Data are presented as median (mean ± SD). Results: 33 patients were included; 17 received preoperative HBO2, and 16 did not. There were no intraoperative or postoperative statistical differences between patients with or without preoperative HBO2. Erythrocyte sedimentation rate (ESR), IL-6, and IL-10 increased slightly before returning to normal, while TGF-alpha decreased before increasing. However, there were no differences with or without HBO2. At postoperative day 30, the pain level measured with VAS score (Visual Analog Score) was lower after HBO2 (1 ± 1.3 vs. 3 ± 3.0, p=0.05). Eleven (76%) patients in the HBO2 cohort and 12 (75%) patients in the non- HBO2 had malignant pathology. The percentage of positive lymph nodes in the HBO2 was 7% compared to 14% in the non-HBO2 (p<0.001). Overall survival was inferior after HBO2 compared to the non- HBO2 (p=0.03). Conclusions: Preoperative HBO2 did not affect perioperative outcomes or significantly change the inflammatory mediators for patients undergoing robotic pancreaticoduodenectomy. Long-term survival was inferior after preoperative HBO2. Further randomized controlled studies are required to assess the full impact of this treatment on patients' prognosis.

In general medicine surplus of care can harm the patients.

Article brings several chosen topics, where in therapy and diagnostic would less be more, that are very often dealt by so called generalists, experts with broad knowledge in medicine. Those are first of all internists and general practitioners.

[Inflammation, malnutrition, and SARS-CoV-2 infection: a disastrous combination]. / La inflamación, la desnutrición y la infección por SARS-CoV-2: una combinación nefasta.

SARS-CoV-2 infection is associated with a high risk of malnutrition, mainly due to increased nutritional requirements and the presence of a severe and universal inflammatory state. Associated symptoms contribute to hyporexia, which perpetuates the negative nutritional balance. Furthermore, dysphagia, especially post-intubation, worsens and makes intake unsafe. This risk is greater in elderly and multimorbid patients. Inflammation to varying degrees is the common link between COVID-19 and the onset of malnutrition, and it is more correct to refer to disease-related malnutrition (DRM). DRM worsens the poor prognosis of SARS-CoV-2 infection, especially in the most severe cases. Therefore, it is necessary to identify and treat people at risk early, avoiding overexposure and direct contact with the patient. We cannot forget the role that a healthy diet plays in both prevention and recovery after discharge.

Curcumin: New Insights into an Ancient Ingredient against Cancer.

Cancer patients frequently use complementary medicine. Curcumin (CUR) and its derivates (from the extract of Curcuma longa L.) represent some of the most frequently used ones, having a long history in traditional Asian medicine. CUR was demonstrated, both in vitro and in vivo, to have significant anti-inflammatory effects, thus potentially counteracting cancer-promoting inflammation, which is a hallmark of cancer. CUR modulate a plethora of signaling pathways in cancer cells, comprising the NF-κB (nuclear factor k-light-chain-enhancer of activated B cells), the JAK/STAT (Janus-Kinase/Signal Transducers and Activators of Transcription), and the TGF-ß (transforming growth factor-ß) pathways. Furthermore, CUR confers properties of electron receptors, which destabilize radical oxygen species (ROS), explaining its antioxidant and anti-apopototic effects. Although CUR has a low bioavailability, its role in advanced cancer treatment and supportive care was addressed in numerous clinical trials. After promising results in phase I⁻II trials, multiple phase III trials in different indications are currently under way to test for direct anti-cancer effects. In addition, CUR exerts beneficial effects on cancer treatment-related neurotoxcity, cardiotoxicity, nephrotoxicity, hemato-toxicity, and others. More efficient galenic formulations are tested to optimze CUR's usability in cancer treatment. This review should provide a comprehensive overview of basic science, and pre-clinical and clinical data on CUR in the field of oncology.

Cold water immersion: kill or cure?

NEW FINDINGS: What is the topic of this review? This is the first review to look across the broad field of 'cold water immersion' and to determine the threats and benefits associated with it as both a hazard and a treatment. What advances does it highlight? The level of evidence supporting each of the areas reviewed is assessed. Like other environmental constituents, such as pressure, heat and oxygen, cold water can be either good or bad, threat or treatment, depending on circumstance. Given the current increase in the popularly of open cold water swimming, it is timely to review the various human responses to cold water immersion (CWI) and consider the strength of the claims made for the effects of CWI. As a consequence, in this review we look at the history of CWI and examine CWI as a precursor to drowning, cardiac arrest and hypothermia. We also assess its role in prolonged survival underwater, extending exercise time in the heat and treating hyperthermic casualties. More recent uses, such as in the prevention of inflammation and treatment of inflammation-related conditions, are also considered. It is concluded that the evidence base for the different claims made for CWI are varied, and although in most instances there seems to be a credible rationale for the benefits or otherwise of CWI, in some instances the supporting data remain at the level of anecdotal speculation. Clear directions and requirements for future research are indicated by this review.

[Tibial defects and infected non-unions : Treatment results after Masquelet technique]. / Tibiadefekt- und Infektpseudarthrosen : Behandlungsergebnisse nach Masquelet-Technik.

BACKGROUND: The treatment of non-unions with large bone defects or osteitis is a major challenge in orthopedic and trauma surgery. A new concept of therapy is a two-step procedure: Masquelet technique according to the diamond concept. METHODS: Between February 2010 and June 2014, 55 patients with tibia non-unions or infections were treated in a two-step Masquelet technique in our center. The patients' average age was 48 (median 50; minimum 15-maximum 72) with an average BMI (body mass index) of 28 (27; 18-52). There were 10 (18 %) female and 45 (82 %) male patients in the group. All study patients went through a follow up. Bone healing and clinical functional data were collected, as well as data according to subjective patient statements about pain and everyday limitations. RESULTS: In 42 cases (76.4 %) the outcome was a sufficient bony consolidation. On average, the time to heal was 10.3 (8, 5; 3-40) months, defect gaps were 4 cm (3 cm; 0,6-26 cm), and on average the patients had had 6 (median 4; range 1-31) previous operations . In all cases patients received osteosynthesis as well as a defect filling with RIA (reamer-irrigator-aspirator), and growth factor BMP-7 (bone morphogenetic protein-7). In 13 cases (23.6 %) there was no therapeutic success. In the evaluation of the SF12 questionnaire the mental health score increased from 47.4 (49.1; 27.6-65.7) to 49.8 (53.0; 28.7-69.4) and the well-being score from 32.7 (32.7;16.9-55.7) to 36.6 (36.5; 24.6-55.9). CONCLUSION: The two-step bone grafting method in the Masquelet technique used for tibia non-unions according to the diamond concept is a promising treatment option. Its application for tibia shaft non-unions with large bone defects or infections means a high degree of safety for the patient.

Inflammation, Immunity, and Hypertension.

The immune system, inflammation and hypertension are related to each other. Innate and adaptive immunity system triggers an inflammatory process, in which blood pressure may increase, stimulating organ damage. Cells in innate immune system produce ROS, such as superoxide and hydrogen peroxide, which aimed at killing pathogens. Long-term inflammation process increases ROS production, causing oxidative stress which leads to endothelial dysfunction. Endothelial function is to regulate blood vessel tone and structure. When inflammation lasts, NO bioavailability decreases, disrupting its main function as vasodilator, so that blood vessels relaxation and vasodilatation are absent. Effector T cells and regulatory lymphocytes, part of the adaptive immune system, plays role in blood vessels constriction in hypertension. Signals from central nervous system and APC activates effector T lymphocyte differentiation and accelerate through Th-1 and Th-17 phenotypes. Th-1 and Th-17 effectors participate in inflammation which leads to increased blood pressure. One part of CD4+ is the regulatory T cells (Tregs) that suppress immune response activation as they produce immunosuppressive cytokines, such as TGF-ß and IL-10. Adoptive transfer of Tregs cells can reduce oxidative stress in blood vessels, endothelial dysfunction, infiltration of aortic macrophages and T cells as well as proinflammatory cytokine levels in plasma circulation.

[Study on main pharmacodynamics and underlying mechanisms of 999 Ganmaoling].

To observe synergistic effects of 999 Ganmaoling (GML) and its Chinese/Western materia medica (CMM and WMM) on pharmacodynamic action and to study underlying mechanisms, their anti-inflammatory, antipyretic effects were compared by assaying the increased capillary permeability induced by glacial acetic acid in mice, ear swelling induced by Xylene in mice, non-specific pleurisy induced by carrageenan in rats, and yeast induced fever in rats. Crystal violet (CV) and microbial activity (XTT) assay were used to evaluate the inhibition of GML and its CMM and WMM on KPN biofilm formation, and scanning electron microscopy (SEM) was applied for observing KPN biofilm morphology changes. The results showed that compared with control group, GML could reduce exudation amount of Evans-Blue and the degree of Ear swelling significantly, and CMM and WMM have no significant effects. The concentration of TNF-α and IL-1ß of rat pleural effusion in GML, CMM and WMM group decreased significantly. The concentration of TNF-α, IL-1ß and IL-8 in GML group, TNF-α, IL-8 in WMM group and IL-8 in CMM in rats serum decreased significantly. The body temperature in rats decreased significantly in GML and WMM group after 4-8 h of administration. CMM group showed no significant difference in rat body temperature compare with control. Compared with control group, GML (55-13.75 g•L⁻¹) could inhibit KPN biofilm formation and reduce number of viable cells in the KPN biofilm. CMM (45-22.5 g•L⁻¹) and WMM (10 g•L⁻¹) could also inhibit KPN biofilm formation and reduce number of viable cells (P<0.01). Result of SEM also showed that GML (55 g•L⁻¹) and its CMM (45 g•L⁻¹) and WMM (10 g•L⁻¹) could interfere the bacterial arrangement of KPN biofilm and extracellular matrix. GML and its CMM & WMM could inhibit the formation of KPN biofilm, CMM & WMM in GML showed synergism and complementation in inhibit KPN biofilm. Results showed that GML had obvious anti-inflammatory and antipyretic effects and could destruct KPN mature biofilm. WMM and CMM showed obvious synergistic effect against inflammation and inhibition of KPN biofilm formation and reduction of number of viable cells but no same effects against fever.

[Topical Use of Cannabis in Inflammatory Diseases in patients of the IPS Salud Social in Barranquilla, Colombia]. / Uso tópico de Cannabis para enfermedades inflamatorias, en pacientes de la IPS Salud Social de Barranquilla.

OBJECTIVE: To relate the topical use of cannabis as an analgesic therapeutic alternative in patients with some inflammatory diseases in Salud Social I.P.S during May to July 2023. METHODS: An analytical, retrospective study was carried out. The population from which the sample was obtained corresponds to patients diagnosed with Arthrosis, Unspecified, Non-Toxic Multinodular Goiter, Epilepsy, Unspecified Type Venous Insufficiency (Chronic) (Peripheral), Unspecified Lumbago, Secondary Gonarthrosis, Rotator Cuff Syndrome, Carpal Tunnel Syndrome, in Salud Social I.P.S of Barranquilla, Atlántico. A sample of 23 patients diagnosed with these pathologies was obtained by non-probabilistic convenience sampling. RESULTS: All patients showed pain relief after two months of follow-up, two experienced adverse effects. Some studies suggest that cannabinoids present in cannabis, such as CBD and THC, may have analgesic and anti-inflammatory properties that could alleviate pain and inflammation associated with these conditions. This is consistent with the present study. CONCLUSION: Topical cannabis is presented as a therapeutic alternative in inflammatory diseases, however, it is important to highlight that research on the use of cannabis in these diseases is limited and more studies are needed to fully understand its effects and potential benefits.

OBJETIVO: Relacionar el uso tópico de cannabis como alternativa terapéutica analgésica en pacientes con algunas enfermedades inflamatorias, de la IPS Salud Social, entre mayo y julio de 2023. MÉTODOS: Se realizó un estudio analítico, retrospectivo. La población de donde se obtuvo la muestra, corresponde a pacientes diagnosticados con Artrosis no especificada, bocio multinodular no tóxico, Epilepsia tipo no especificado, insuficiencia venosa crónica y periférica, Lumbago no especificado, gonartrosis secundaria, síndrome de manguito rotador, síndrome del túnel carpiano, de la IPS Salud Social de Barranquilla, Atlántico. Se obtuvo una muestra de 23 pacientes diagnosticados con estas patologías mediante muestreo no probabilístico por conveniencia. RESULTADOS: Todos los pacientes mostraron alivio del dolor, después de dos meses de seguimiento; dos experimentaron efectos adversos. Algunos estudios sugieren que los cannabinoides presentes en el cannabis, como el CBD y el THC, podrían tener propiedades analgésicas y antiinflamatorias que podrían aliviar el dolor y la inflamación asociados con estas afecciones, lo que es coherente con el presente estudio. CONCLUSIÓN: El cannabis tópico se presenta como una alternativa terapéutica para enfermedades inflamatorias, sin embargo, es importante destacar que la investigación sobre el uso del cannabis en estas enfermedades es limitada y se necesitan más estudios para comprender completamente sus efectos y beneficios potenciales.

Allergic Airway Inflammation Emerges from Gut Inflammation and Leakage in Mouse Model of Asthma.

Asthma is an allergic airway inflammatory disease characterized by type 2 immune responses. Growing evidence suggests an association between allergic airways and intestinal diseases. However, the primary site of disease origin and initial mechanisms involved in the development of allergic airway inflammation (AAI) is not yet understood. Therefore, the initial contributing organs and mechanisms involved in the development of AAI are investigated using a mouse model of asthma. This study, without a local allergen challenge into the lungs, demonstrates a significant increase in intestinal inflammation with signature type-2 mediators including IL-4, IL-13, STAT6, eosinophils, and Th2 cells. In addition, gut leakage and mRNA expressions of gut leakage markers significantly increase in the intestine. Moreover, reduced mRNA expressions of tight junction proteins are observed in gut and interestingly, in lung tissues. Furthermore, in lung tissues, an increased pulmonary barrier permeability and IL-4 and IL-13 levels associated with significant increase of lipopolysaccharide-binding protein (LBP-gut leakage marker) and eosinophils are observed. However, with local allergen challenges into the lungs, these mechanisms are further enhanced in both gut and lungs. In conclusion, the primary gut originated inflammatory responses translocates into the lungs to orchestrate AAI in a mouse model of asthma.

The mannose receptor is expressed by olfactory ensheathing cells in the rat olfactory bulb.

Complex carbohydrate structures are essential molecules of infectious bacteria, parasites, and host cells and are involved in cell signaling associated with immune responses, glycoprotein homeostasis, and cell migration. The uptake of mannose-tailed glycans is usually carried out by professional phagocytes to trigger MHC class I- and MHC class II-restricted antigen presentation or, alternatively, to end inflammation. We have detected the mannose receptor (MR) in cultured olfactory ensheathing cells (OECs), so we investigated by flow cytometry whether recently dissociated cells of the olfactory bulb (OB) nerve fiber layer (ONL) could bind a mannosylated ligand (fluorescein conjugate of mannosyl bovine serum albumin; Man/BSA-FITC) in a specific manner. In addition, we estimated the relative proportion of ONL OECs, microglia, and astrocytes, tagged by 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), by the B4 isolectin of Griffonia simplicifonia (IB4), and by glial fibrillary acidic protein (GFAP), respectively, that were Man/BSA-FITC(+) . We also determined by histochemistry and/or immunohistochemistry whether Man/BSA-FITC or an anti-MR antibody (anti-C-terminal MR peptide; anti-cMR) labeled OECs and/or parenchymal microglia. In addition, we confirmed by Western blot with the K1K2 (against the entire MR molecule) antibody that a band of about 180 kDA is expressed in the OB. Our findings are compatible with a prospective sentinel role of OECs against pathogens of the upper airways and/or damage-associated glycidic patterns as well as with homeostasis of OB mannosylated glycoproteins.

Turmeric supplementation improves markers of recovery in elite male footballers: a pilot study.

Football match-play causes muscle damage and provokes an inflammatory response. Rapid recovery is paramount to optimising subsequent performance and reducing injury risk. Turmeric contains high concentrations of curcumin, a polyphenol that has been shown to reduce muscle damage and soreness post-exercise in recreational exercisers. However, it is unknown whether a curcumin-containing supplement can support elite footballers recovery between matches. This applied study explored whether a turmeric supplement could improve performance, subjective and physiological markers of recovery, in elite male footballers. Twenty-four elite male footballers divided into a turmeric group, who consumed 60 mL of a turmeric drink twice per day, or a control group who did not. After 96 h of rest, baseline measurements of subjective soreness (leg and whole-body), plasma creatine kinase ([CK]), plasma C-reactive protein ([CRP]), isometric mid-thigh pull (IMTP) and counter movement jump (CMJ), were collected. Following eight competitive matches, subjective leg and whole-body soreness and plasma concentrations of inflammation markers ([CK] and [CRP]) were assessed immediately (0 h), 40 and 64 h post-match. Performance markers (IMTP and CMJ) were also assessed at 40 and 64 h post-match. Percentage change from baseline showed a main effect of group (p = 0.035, p = 0.005) and time (p = 0.002, p = 0.002) for both leg and whole-body soreness, respectively. There was a group by time interaction effect (p = 0.049) for [CRP]. There were no effects of turmeric on [CK], CMJ or IMTP. This applied study is the first in elite footballers to show that a curcumin-containing supplementation may attenuate a biomarker of inflammation [CRP] and soreness post-match play.

Tanshinone IIA inhibits cardiomyocyte pyroptosis through TLR4/NF-κB p65 pathway after acute myocardial infarction.

Background: Tanshinone IIA, derived from Radix Salviae Miltiorrhizae (Salvia miltiorrhiza Bunge), constitutes a significant component of this traditional Chinese medicine. Numerous studies have reported positive outcomes regarding its influence on cardiac function. However, a comprehensive comprehension of the intricate mechanisms responsible for its cardioprotective effects is still lacking. Methods: A rat model of heart failure (HF) induced by acute myocardial infarction (AMI) was established via ligation of the left anterior descending coronary artery. Rats received oral administration of tanshinone IIA (1.5 mg/kg) and captopril (10 mg/kg) for 8 weeks. Cardiac function was assessed through various evaluations. Histological changes in myocardial tissue were observed using staining techniques, including Hematoxylin and Eosin (HE), Masson, and transmission electron microscopy. Tunel staining was used to detect cell apoptosis. Serum levels of NT-pro-BNP, IL-1ß, and IL-18 were quantified using enzyme-linked immunosorbent assay (ELISA). Expression levels of TLR4, NF-κB p65, and pyroptosis-related proteins were determined via western blotting (WB). H9C2 cardiomyocytes underwent hypoxia-reoxygenation (H/R) to simulate ischemia-reperfusion (I/R) injury, and cell viability and apoptosis were assessed post treatment with different tanshinone IIA concentrations (0.05 µg/ml, 0.1 µg/ml). ELISA measured IL-1ß, IL-18, and LDH expression in the cell supernatant, while WB analysis evaluated TLR4, NF-κB p65, and pyroptosis-related protein levels. NF-κB p65 protein nuclear translocation was observed using laser confocal microscopy. Results: Tanshinone IIA treatment exhibited enhanced cardiac function, mitigated histological cardiac tissue damage, lowered serum levels of NT-pro-BNP, IL-1ß, and IL-18, and suppressed myocardial cell apoptosis. Moreover, tanshinone IIA downregulated the expression of TLR4, NF-κB p65, IL-1ß, pro-IL-1ß, NLRP3, Caspase-1, and GSDMD-N pyroptosis-related proteins in myocardial tissue. Additionally, it bolstered H/R H9C2 cardiomyocyte viability, curbed cardiomyocyte apoptosis, and reduced the levels of TLR4, NF-κB p65, IL-1ß, pro-IL-1ß, NLRP3, Caspase-1, and GSDMD-N pyroptosis-related proteins in H/R H9C2 cells. Furthermore, it hindered NF-κB p65 protein nuclear translocation. Conclusion: These findings indicate that tanshinone IIA enhances cardiac function and alleviates myocardial injury in HF rats following AMI. Moreover, tanshinone IIA demonstrates potential suppression of cardiomyocyte pyroptosis. These effects likely arise from the inhibition of the TLR4/NF-κB p65 signaling pathway, presenting a promising therapeutic target.

Relationships Between Systemic Inflammatory Markers and 18F-FDG PET/CT Imaging and Clinical Findings in Pulmonary Sarcoidosis.

Background and aim Sarcoidosis is a multisystem inflammatory disease of unknown aetiology. This study aimed to evaluate the relationship between systemic inflammatory parameters, the systemic immune-inflammation index (SII) and the lymphocyte-to-monocyte ratio (LMR), and disease stage, clinical findings, and 18F-fluoro-2-deoxy-D-glucose (18F-FDG) tomography/computed tomography (PET/CT) uptake. Materials and methods Our study included 73 patients. The general characteristics, radiological features, spirometric tests, PET/CT findings, and laboratory parameters of the patients were recorded. Results Relapse and parenchymal fibrosis were not associated with metabolic parameters, such as LMR and SII. Serum angiotensin-converting enzyme (ACE) levels were lower in the relapsed group than in the non-relapse group. However, the patients' PET/CT images indicated that 18F-FDG parenchym maximum standard uptake value (SUV max), lymph node SUV max, lymph node short axis dimension, SII, and LMR were similar between all patients, relapsed or not. Conclusion Although found to be significant in other inflammatory diseases, we found that SII and LMR alone did not indicate disease prognosis in sarcoidosis due to the small number of patients and the lack of homogeneity between the groups in our study. The usefulness of these markers for clinical use should be investigated by studies that include those with extrapulmonary sarcoidosis, and that calculate these markers at the time of disease diagnosis and during the post-treatment period.

Lianhua Qingke ameliorates lipopolysaccharide-induced lung injury by inhibiting neutrophil extracellular traps formation and pyroptosis.

LHQK is a patented Traditional Chinese Medicine (TCM) which is clinically used for acute tracheobronchitis, cough, and other respiratory diseases. Recent studies have proved that LHQK exhibits excellent clinical efficacy in the treatment of acute lung injury (ALI). However, the corresponding mechanisms remain largely unexplored. In this study, we investigated the effects and the underlying mechanisms of LHQK on lipopolysaccharide (LPS)-induced ALI in mice. The pathological examination, inflammatory cytokines assessments, and mucus secretion evaluation indicated that administration of LHQK ameliorated LPS-induced lung injury, and suppressed the secretion of Muc5AC and pro-inflammatory cytokines (IL-6, TNF-α, and IL-1ß) in plasma and BALF. Furthermore, the results of cell-free DNA level showed that LHQK significantly inhibited LPS-induced NETs formation. Western blot revealed that LHQK effectively inhibited LPS-triggered pyroptosis in the lung. In addition, RNA-Seq data analysis, relatively bioinformatic analysis, and network pharmacology analysis revealed that LHQK and relative components may play multiple protective functions in LPS-induced ALI/acute respiratory distress syndrome (ARDS) by regulating multiple targets directly or indirectly related to NETs and pyroptosis. In conclusion, LHQK can effectively attenuate lung injury and reduce lung inflammation by inhibiting LPS-induced NETs formation and pyroptosis, which may be regulated directly or indirectly by active compounds of LHQK.

Traditional Chinese medicine promotes the control and treatment of dementia.

Dementia is a syndrome that impairs learning and memory. To date, there is no effective therapy for dementia. Current prescription drugs, such as cholinesterase inhibitors, fail to improve the condition of dementia and are often accompanied by severe adverse effects. In recent years, the number of studies into the use of traditional Chinese medicine (TCM) for dementia treatment has increased, revealing a formula that could significantly improve memory and cognitive dysfunctions in animal models. TCM showed fewer adverse effects, lower costs, and improved suitability for long-term use compared with currently prescribed drugs. Due to the complexity of ingredients and variations in bioactivity of herbal medicines, the multi-target nature of the traditional Chinese formula affected the outcome of dementia therapy. Innovations in TCM will create a platform for the development of new drugs for the prevention and treatment of dementia, further strengthening and enhancing the current influence of TCM.

Galectin-3 as a Potential Prognostic Biomarker for COVID-19 Disease: A Case-Control Study.

Background Recent studies have investigated the importance of Galetin-3 in inflammation, fibrosis, cell proliferation, cardiac disease, diabetes, and tumor formation. Aims This study aims to investigate the role of the Galectin-3 level in the diagnosis of COVID-19 pneumonia and the value of the Galectin-3 level in predicting the clinical course of the patient. Methods This study employed a prospective, case-control study design and was conducted at Bakircay University Cigli Training and Research Hospital. A total of 100 patients (40 had moderate and 60 had severe/critical COVID-19 disease according to World Health Organisation guidelines) and 50 non-symptomatic healthy volunteers participated in the study. Blood samples were taken from patients at the time of hospital admission, after which serum was isolated. Following the isolation of serum, Galectin-3 levels were evaluated using the enzyme-linked immunosorbent assay (ELISA) method.  Results The serum Galectin-3 level was measured as 13.57 (10.9-16.4) ng/mL in the control group, 13.52 (10.69-16.6) ng/mL in the moderate disease group, and 11.65 (6.09-14.33) ng/mL in the severe/critical disease group. Serum Galectin-3 levels were significantly lower in the severe/critical disease group compared to the control and moderate disease groups (p=0.001 and p=0.019, respectively). Using ROC analysis, a larger area under the curve (AUC) for the serum Galectin-3 levels of the control group (AUC=0.622, 95% CI =0.529-0.714; p=0.015) was calculated compared to the COVID-19 patient group for the diagnosis of COVID-19 disease. The Galectin-3 level was found to be 75% sensitive and 50% specific at a cut-off level of 11.3 ng/mL in predicting the need for ICU treatment. Conclusion Galectin-3 levels may be a beneficial biomarker in predicting the clinical severity of COVID-19 disease when used in conjunction with other known biomarkers, at the time of admission to the emergency department (ED).

A novel reactive aldehyde species inhibitor prevents the deleterious effects of ethanol in an animal model of alcoholic liver disease.

BACKGROUND AND AIMS: Current treatment strategies for alcoholic liver disease (ALD) are limited by the lack of agents specifically targeting the metabolic breakdown products of ethanol. Reactive aldehyde species (RASP) inhibitors have been developed that have the capability to sequester these aldehyde byproducts, potentially limiting toxicity. The purpose of this study was to determine if the RASP inhibitor ADX-629 could target these metabolic breakdown products in a mouse model of ALD. METHODS AND RESULTS: A chronic/binge mouse model of ALD was used to determine the efficacy of ADX-629 treatment. Mice were fed an alcohol-containing (5 %) liquid or control diet for 10 days and treated by oral gavage with ADX-629 30 min prior to administering a bolus gavage of 31.5 % ethanol. Test groups included: Control - no ADX, Control + ADX, Ethanol - no ADX and Ethanol + ADX. Compared to ethanol-fed mice receiving sham treatment, ethanol mice treated with ADX-629 demonstrated significant decreases (p < 0.05) in liver acetaldehyde (AA), liver malondialdehyde-acetaldehyde (MAA), circulating anti-MAA antibody, liver/serum triglycerides (p < 0.01) levels, and overall fat accumulation in the liver as determined by Oil Red O and bodipy staining (p < 0.0001). Serum levels of pro-inflammatory cytokines IFN-γ and MCP-1 levels were decreased following ADX-629 treatment (p < 0.01). CONCLUSIONS: These findings demonstrate that the use of this unique RASP inhibitor (ADX-629) is effective in the treatment of ALD. Given the ubiquitous nature of aldehydes in the context of tissue inflammation and damage, ADX-629 and other RASP inhibitors may have additional applications in disease states.

The Roles of Heat Shock Protein-60 and 70 and Inflammation in Obesity-Related Kidney Disease.

Introduction The exact mechanisms of obesity-related kidney disease (ORKD) are not fully known. Heat shock proteins (HSPs) may play a role in ORKD mechanisms because of their role in cell apoptosis, cytoprotection, and inflammatory processes. We aimed to determine the role of circulating serum HSP-60 and HSP-70 levels as a biomarker for ORKD. Materials and methods This study included 40 ORKD patients, 40 obese age-matched and sex-matched controls with similar body mass index (BMI), and 40 healthy controls. Their serum biochemical and hemogram parameters as well as HSP-60 and HSP-70 levels were evaluated and compared. Their neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein levels were assessed to define inflammation.  Results The patients had significantly higher HSP-60 levels than the obese and healthy controls (537.58 ± 170.35, 430.80 ± 110.61, and 371.85 ± 76.34, respectively; p<0.00). The results revealed that the 24-hour urinary protein levels had a positive correlation (r= 0.544), whereas the glomerular filtration rate had a negative correlation (r = 0.38) with the serum HSP-60 level. According to the regression analysis performed on the HSP-60 and 24-hour urinary protein excretion levels, an increase in the HSP-60 level significantly increased the 24-hour urinary protein excretion rate (r=0.15; p<0.005). The HSP-60 levels were correlated with inflammatory markers Conclusion The serum HSP-60 levels increased in patients with ORKD. This increase was correlated with 24-hour urinary protein excretion. Increased circulating levels of HSP-60 may play a role in the initiation and/or progression of renal damage and inflammation. HSP-60 is a potential biomarker for ORKD. However, additional information and studies are required to further elucidate this finding.