Psoralen protects neurons and alleviates neuroinflammation by regulating microglial M1/M2 polarization via inhibition of the Fyn-PKCδ pathway.

Microglia-mediated neuroinflammation is closely associated with many neurodegenerative diseases. Psoralen has potential for the treatment of many diseases, however, the anti-neuroinflammatory and neuroprotective effects of psoralen have been unclear. This study investigated the anti-neuroinflammatory and neuroprotective effects of psoralen and its regulation of microglial M1/M2 polarization. The LPS-induced mice model was used to test anti-neuroinflammatory effects, regulatory effects on microglia polarization, and neuroprotective effects of psoralen in vivo. The LPS-induced BV2 model was used to test the anti-neuroinflammatory effects and the regulatory effects and mechanisms on microglial M1/M2 polarization of psoralen in vitro. PC12 cell model induced by conditioned medium of BV2 cells was used to validate the protective effects of psoralen against neuroinflammation-induced neuronal damage. These results showed that psoralen inhibited the expression of iNOS, CD86, and TNF-α, and increased the expression of Arg-1, CD206, and IL-10. These results indicated that psoralen inhibited the M1 microglial phenotype and promoted the M2 microglial phenotype. Further studies showed that psoralen inhibited the phosphorylation of Fyn and PKCδ, thereby inhibiting activation of the MAPKs and NF-κB pathways and suppressing the expression of pro-inflammatory cytokines in microglia. Furthermore, psoralen reduced oxidative stress, neuronal damage, and apoptosis via inhibition of neuroinflammation. For the first time, this study showed that psoralen protected neurons and alleviated neuroinflammation by regulating microglial M1/M2 polarization, which may be mediated by inhibition of the Fyn-PKCδ pathway. Thus, psoralen may be a potential agent in the treatment of neuroinflammation-related diseases.

Optimized reusable modular 3D-printed models of choledochal cyst to simulate laparoscopic and robotic bilioenteric anastomosis.

Laparoscopic and robotic surgery is a challenge to the surgeon's hand-eye coordination ability, which requires constant practice. Traditional mentor training is gradually shifting to simulation training based on various models. Laparoscopic and robotic bilioenteric anastomosis is an important and difficult operation in hepatobiliary surgery. We constructed and optimized the reusable modular 3D-printed models of choledochal cyst. The aim of this study was to verify the ability of this optimized model to distinguish between surgeons with different levels of proficiency and the benefits of repeated practice. A total of 12 surgeons with different levels participated in the study. Operation completion time and OSATS score were recorded. The model was validated by Likert scale. Surgeons were shown the steps and contents before performing laparoscopic or robotic bilioenteric anastomosis using the model. Surgeons with different levels of experience showed different levels when performing laparoscopic bilioenteric anastomosis on this model. Repeated training can significantly shorten the time of laparoscopic bilioenteric anastomosis and improve the operation scores of surgeons with different levels of experience. At the same time, preliminary results have shown that the performance of surgeons on the domestic robotic platform was basically consistent with their laparoscopic skills. This model may distinguish surgeons with different levels of experience and may improve surgical skills through repeated practice. It is worth noting that in order to draw more reliable conclusions, more subjects should be collected and more experiments should be done in the future.

Tuberculosis in pregnancy and assisted reproductive technology.

Tuberculosis is a chronic infectious disease caused by mycobacterium tuberculosis infection. In the world, tuberculosis is an important factor affecting women's reproductive health, which can cause reproductive tract anatomy abnormalities, embryo implantation obstacles, ovarian reserve and ovulation dysfunction, leading to female infertility. This group of women usually need to seek assisted reproductive technology to conceive. Latent tuberculosis infection during pregnancy has no clinical manifestation, but may develop into active tuberculosis, leading to adverse pregnancy outcomes. Most pregnant women do not need to be treated for latent tuberculosis infection, unless they are combined with high-risk factors for tuberculosis progress, but they need close follow-up. Early diagnosis and treatment of active tuberculosis in pregnancy can reduce the incidence rate and mortality of pregnant women and newborns, and treatment needs multidisciplinary cooperation.

Nuclear Factor Erythroid 2 Related Factor 2 and Mitochondria Form a Mutually Regulating Circuit in the Prevention and Treatment of Metabolic Syndrome.

Significance: Metabolic syndrome (MetS) has become a major global public health problem and there is an urgent need to elucidate its pathogenesis and find more effective targets and modalities for intervention. Recent Advances: Oxidative stress and inflammation are two of the major causes of MetS-related symptoms such as insulin resistance and obesity. Nuclear factor erythroid 2 related factor 2 (Nrf2) is one of the important systems responding to oxidative stress and inflammation. As cells undergo stress, cysteines within Kelch-like ECH-associated protein 1 (Keap1) are oxidized or electrophilically modified, allowing Nrf2 to escape ubiquitination and be translocated from the cytoplasm to the nucleus, facilitating the initiation of the antioxidant transcriptional program. Meanwhile, a growing body of evidence points out a specific modulation of mitochondrial homeostasis by Nrf2. After nuclear translocation, Nrf2 activates downstream genes involved in various aspects of mitochondrial homeostasis, including mitochondrial biogenesis and dynamics, mitophagy, aerobic respiration, and energy metabolism. In turn, mitochondria reciprocally activate Nrf2 by releasing reactive oxygen species and regulating antioxidant enzymes. Critical Issues: In this review, we first summarize the interactions between Nrf2 and mitochondria in the modulation of oxidative stress and inflammation to ameliorate MetS, then propose that Nrf2 and mitochondria form a mutually regulating circuit critical to maintaining homeostasis during MetS. Future Directions: Targeting the Nrf2-mitochondrial circuit may be a promising strategy to ameliorate MetS, such as obesity, diabetes, and cardiovascular diseases.

The effect of the female genital tract and gut microbiome on reproductive dysfunction.

Microorganisms are ubiquitous in the human body; they are present in various areas including the gut, mouth, skin, respiratory tract, and reproductive tract. The interaction between the microbiome and reproductive health has become an increasingly compelling area of study. Disruption of the female genital tract microbiome can significantly impact the metabolism of amino acids, carbohydrates, and lipids, increasing susceptibility to reproductive tract diseases such as vaginitis, chronic endometritis, endometrial polyps, endometriosis, and polycystic ovary syndrome. The gut microbiome, considered an endocrine organ, plays a crucial role in the reproductive endocrine system by interacting with hormones like estrogen and androgens. Imbalances in the gut microbiome composition can lead to various diseases and conditions, including polycystic ovary syndrome, endometriosis, and cancer, although research on their mechanisms remains limited. This review highlights the latest advancements in understanding the female genital tract and gut microbiomes in gynecological diseases. It also explores the potential of microbial communities in the treatment of reproductive diseases. Future research should focus on identifying the molecular mechanisms underlying the association between the microbiome and reproductive diseases to develop new and effective strategies for disease prevention, diagnosis, and treatment related to female reproductive organs.

Comparative Study of Hydroxytyrosol Acetate and Hydroxytyrosol in Activating Phase II Enzymes.

Nuclear factor E2-related factor 2 (Nrf2) is fundamental to the maintenance of redox homeostasis within cells via the regulation of a series of phase II antioxidant enzymes. The unique olive-derived phenolic compound hydroxytyrosol (HT) is recognized as an Nrf2 activator, but knowledge of the HT derivative hydroxytyrosol acetate (HTac) on Nrf2 activation remains limited. In this study, we observed that an HT pretreatment could protect the cell viability, mitochondrial membrane potential, and redox homeostasis of ARPE-19 cells against a t-butyl hydroperoxide challenge at 50 µM. HTac exhibited similar benefits at 10 µM, indicating a more effective antioxidative capacity compared with HT. HTac consistently and more efficiently activated the expression of Nrf2-regulated phase II enzymes than HT. PI3K/Akt was the key pathway accounting for the beneficial effects of HTac in ARPE-19 cells. A further RNA-Seq analysis revealed that in addition to the consistent upregulation of phase II enzymes, the cells presented distinct expression profiles after HTac and HT treatments. This indicated that HTac could trigger a diverse cellular response despite its similar molecular structure to HT. The evidence in this study suggests that Nrf2 activation is the major cellular activity shared by HTac and HT, and HTac is more efficient at activating the Nrf2 system. This supports its potential future employment in various disease management strategies.

Risk factors and biomarkers for post-tuberculosis lung damage in a Chinese cohort of male smokers and non-smokers: protocol for a prospective observational study.

INTRODUCTION: Post-tuberculosis lung damage (PTLD) refers to the residual pulmonary impairment following the completion of antituberculosis (TB) therapy, characterised by persistent respiratory symptoms and abnormal pulmonary function. The risk factors and biomarkers for PTLD have been scarcely investigated. More importantly, whether and to what extent cigarette smoking is involved in PTLD remain to be known. METHODS AND ANALYSIS: This prospective observational study will enrol 400 male smoking or non-smoking patients aged 25-65 years, with newly confirmed active TB between 2022 and 2024, from the Department of Respiratory and Critical Care Medicine at Peking University Third Hospital and the Tuberculosis Department at Beijing Geriatric Hospital. Because females rarely smoke in China, we will enrol only males in this study. Demographic data, smoking history and amount, clinical symptoms, lung function, and chest CT findings will be prospectively collected. Respiratory questionnaires, lung function measurements and chest CT examinations will be performed immediately after, and 1 year, 2 years and 3 years after the completion of TB treatment. Peripheral blood samples will be obtained at baseline and at the end of anti-TB therapy, and a Luminex xMAP-based multiplex immunoassay will be used to measure inflammatory mediators and cytokines in serum. The collected data will be analysed to determine the incidence and factors/biomarkers of PTLD according to smoking status. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Peking University Third Hospital (approval number: (2022)271-03; approval date: 8 June 2022). The research results will be disseminated through scientific and medical conferences and will be published in an academic journal. TRIAL REGISTRATION NUMBER: NCT04966052.

Synthesis, biological and molecular docking studies of pyrimidine-derived bioactive Schiff bases.

Pyrimidine which is an important constituent of the genetic material of deoxyribonucleic acid, is identified with a large number of biological activities. Based on this, pyrimidine-derived Schiff bases (1-6) of hydroxy-1-naphthaldehyde were synthesized by using the condensation method. In addition, the molecular docking studies against topoisomerase II DNA gyrase, human hematopoietic cell kinase, urate oxidase from Aspergillus flavus, and cyclin-dependent kinase 8 to explore the antibacterial, antioxidant, antifungal, and anticancer properties respectively and binding affinities through bioinformatics approaches to determine the interaction among active molecules with the receptor. Hence, the computational docking analyses identified that all synthesized pyrimidine Schiff bases (1-6) are active and exhibited better binding affinities as compared to the standard drugs. Furthermore, all the prepared materials were characterized by using nuclear magnetic resonance, infrared, and elemental analysis. Additionally, the phase-transition and thermal decomposition temperatures were determined by differential scanning calorimetry and thermo-gravimetric analysis measurements. Moreover, the structures of pyrimidine-derived Schiff bases 1, 2, 3, 4, and 5 were also confirmed by the X-ray single-crystal diffraction technique. The pyrimidine-derived Schiff bases 5 possess significant antibacterial, antioxidant, antifungal, and anticancer agent properties which confirms its promising biological activities over standard drugs.

Effect of Chinese patent medicine Kunling Pill on endometrial receptivity: A clinical trial, network pharmacology, and animal-based study.

Although pregnancy success rates are raised with assisted reproductive technology, it still cannot meet clinical demands. Kunling Pill (KLP), a traditional Chinese medicine, is widely used in various gynecological disorders, particularly in improving fertility and pregnancy rates. However, the underlying mechanism of how KLP affects pregnancy outcomes remains unclear. This study aimed to explore the effects and mechanisms of KLP on endometrial receptivity. Firstly, a retrospective trial was conducted to validate the efficacy of KLP on repeated implantation failure (RIF) patients. The result indicated a significant increase in the proportion of live birth in KLP group (30.56%) compared to the control group (16.89%). Secondly, network pharmacology methods predicted the active components and network targets of KLP. Endometrial receptivity is closely associated with the activation of inflammatory factors, predicting the function of KLP on the immune system. The estrogen and apoptotic signaling pathways were also highlighted in the gene ontology enrichment analysis. Thirdly, a decreased endometrial receptivity model was established by controlled ovarian hyperstimulation (COH) in female C57BL/6 mice, divided into the COH and KLP groups. Normal female mice are as control group. In vivo, KLP administration could increase endometrial thickness and the number of endometrial glands and pinopodes. In the endometrium, KLP supplementation upregulated the expressions of estrogen receptor α, progesterone receptor, endothelial nitric oxide synthase, and integrin αVß3 in the murine uterus and reduced serum levels of estrogen and progesterone. KLP regulated the uterine immune cells and inhibited cell apoptosis in the ovary via Bcl-2/Bax/caspase-3 pathway. In conclusion, KLP administration raised the live birth rate in RIF patients to optimize medication regimens, mainly because KLP ameliorated impaired endometrial receptivity.

Higher serum AMH level is associated with better pregnancy outcomes of IVF/ICSI assisted pregnancy in infertile patients under 35 years old.

This study aimed to investigate the effect of anti-Mullerian hormone (AMH) on the pregnancy outcome of infertility assisted by IVF/Micro-Insemination/Embryo Transfer Infertility Assistance (IVF/ICSI-ET). A total of 324 patients under the age of 35 who received IVF/ICSI-ET assistance in our center were included in this analysis. AMH levels of these patients were measured by chemiluminescence method and divided into clinical pregnancy group (175 cases) and non-pregnancy group (149 cases) according to the final pregnancy outcome. The relationship between the two groups' pregnancy outcomes and AMH levels was analyzed. The above association was re-evaluated after excluding patients with polycystic ovary syndrome. There was no significant difference in age, body mass index (BMI), follicle-stimulating hormone (FSH), and 2 pronucleus (PN) between clinical and non-clinical pregnancy groups. Compared with the clinical pregnancy group, the level of AMH in the non-pregnancy group was significantly lower (p < 0.05). A higher AMH level was closely related to better IVF/ICSI-ET assisted pregnancy outcome in vitro. After excluding AMH abnormalities, the AMH level was still significantly associated with pregnancy outcomes of in vitro IVF/ICSI-ET-assisted pregnancy. Our results show a correlation between AMH level and pregnancy outcome of in vitro IVF/ICSI-ET assisted pregnancy. For women under age 35, lower AMH levels may be one of the predictors of adverse pregnancy outcomes. For patients with low AMH level, it is suggested to strengthen monitoring to ensure the safety and smoothness of the pregnancy process.

Apolipoprotein E deficiency attenuated osteogenesis via down-regulating osterix.

Apolipoprotein E (ApoE), a ligand for low-density lipoprotein receptors, is strongly induced during osteogenesis and has a physiologic role in regulating osteoblast function, but the mechanisms of its action are still unclear. The study aims to elucidate the influence and molecular mechanisms of ApoE on bone formation. An ovariectomy-induced osteoporotic model were conducted in ApoE knockout (ApoE-/-) mice to study the effect of ApoE on the bone system. Bone quality were assessed through bone mineral density and histomorphometric analysis. To investigate the underlying role and mechanisms of ApoE during osteogenesis, primary osteoblasts from the calvariums of newborn ApoE-/- or wild-type (WT) mice were cultured in the osteoblastic differentiation medium in vitro for further research. Our animal experiment data showed that ApoE-/- mice exhibited bone loss, exacerbated by estrogen deprivation after ovariectomy. ApoE deficiency attenuated osteoblast activity and inhibited osteoblast osteogenesis, accompanied by decreased osterix expression. ApoE deficiency did not affect primary osteoblast viability and collagen-1 expression. Moreover, osteoprotegerin expression in ApoE-/- osteoblasts was reduced compared to WT controls. Our study demonstrated that ApoE gene deficiency contributed to bone loss and attenuated osteogenesis by down-regulating osterix expression.

The role of placental aging in adverse pregnancy outcomes: A mitochondrial perspective.

Premature placental aging is associated with placental insufficiency, which reduces the functional capacity of the placenta, leading to adverse pregnancy outcomes. Placental mitochondria are vital organelles that provide energy and play essential roles in placental development and functional maintenance. In response to oxidative stress, damage, and senescence, an adaptive response is induced to selectively remove mitochondria through the mitochondrial equivalent of autophagy. However, adaptation can be disrupted when mitochondrial abnormalities or dysfunctions persist. This review focuses on the adaptation and transformation of mitochondria during pregnancy. These changes modify placental function throughout pregnancy and can cause complications. We discuss the relationship between placental aging and adverse pregnancy outcomes from the perspective of mitochondria and potential approaches to improve abnormal pregnancy outcomes.

Assembly of mitochondrial succinate dehydrogenase in human health and disease.

Mitochondrial succinate dehydrogenase (SDH), also known as electron transport chain (ETC) Complex II, is the only enzyme complex engaged in both oxidative phosphorylation and the tricarboxylic acid (TCA) cycle. SDH has received increasing attention due to its crucial role in regulating mitochondrial metabolism and human health. Despite having the fewest subunits among the four ETC complexes, functional SDH is formed via a sequential and well-coordinated assembly of subunits. Along with the discovery of subunit-specific assembly factors, the dynamic involvement of the SDH assembly process in a broad range of diseases has been revealed. Recently, we reported that perturbation of SDH assembly in different tissues leads to interesting and distinct pathophysiological changes in mice, indicating a need to understand the intricate SDH assembly process in human health and diseases. Thus, in this review, we summarize recent findings on SDH pathogenesis with respect to disease and a focus on SDH assembly.

Contemplating the necessity of surgical treatment for posterior lenticonus: a case report.

BACKGROUND: Posterior lenticonus is an uncommon congenital abnormality that causes a progressive, localized spherical or conical bulging of the posterior capsular membrane, resulting in an abnormal shape of the lens. CASE PRESENTATION: A 13-year-old girl presented with ametropia in both eyes. After mydriasis, examination revealed an oval bubble-shaped alteration with a distinct boundary above the temporal region on the center of the posterior capsule of her left lens. The subcortical region surrounding the alteration appeared feathery and turbid. The patient had no history of trauma or family history of visual impairment. Systemic investigations were normal. A thorough eye examination was performed, which included optometry, ultrasound biomicroscopy, ocular B-Scan, and anterior segment optical coherence, to assess the disease. The patient was diagnosed with posterior lenticonus in the left eye, as well as ametropia and anisometropia in both eyes. Conservative treatment was initiated since the patient's current best corrected visual acuity was good, and regular monitoring of the condition's progression was scheduled. CONCLUSIONS: This case report presents a rare instance of posterior lenticonus. The findings of this report raise new considerations regarding the necessity of surgical intervention for this condition.

Splicing oxygen-rich multidentate ligands and characteristic metals to construct flame colorants: abundant structures and attractive colors.

Tetranitroethane (TNE), an energetic compound with high-nitrogen (N%, 26.7%) and oxygen (O%, 60.9%) content, is deprotonated by alkali and alkaline earth metal bases to form the corresponding metal salts of TNE which are characterized by FT-IR spectroscopy, elemental analysis, and single crystal X-ray diffraction. All the prepared energetic metal salts show excellent thermal stabilities, and the decomposition temperatures of EP-3, EP-4, and EP-5 are higher than 250 °C, due to the numerous coordination bonds of the complexes. Furthermore, the energy of formation of the nitrogen-rich salts were calculated utilizing heat of combustion. The detonation performances were calculated with the EXPLO5 software, and the impact and friction sensitivities were determined. EP-7 shows excellent energy performance (P = 30.0 GPa, VD = 8436 m s-1). EP-3, EP-4, EP-5, and EP-8 are more sensitive to mechanical stimulation. These alkali and alkaline earth metal salts of TNE show good monochromaticity by atomic emission spectroscopy (visible light), and may be used as potential flame colorants in pyrotechnics.

Correlation evaluation between cancer microenvironment related genes and prognosis based on intelligent medical internet of things.

The study of tumor microenvironment plays an important role in the treatment of cancer patients. In this paper, intelligent medical Internet of Things technology was used to analyze cancer tumor microenvironment-related genes. Through experiments designed and analyzed cancer-related genes, this study concluded that in cervical cancer, patients with high expression of P16 gene had a shorter life cycle and a survival rate of 35%. In addition, through investigation and interview, it was found that patients with positive expression of P16 and Twist genes had a higher recurrence rate than patients with negative expression of both genes; high expression of FDFT1, AKR1C1, and ALOX12 in colon cancer is associated with short survival; high expressions of HMGCR and CARS1 is associated with longer survival; overexpression of NDUFA12, FD6, VEZT, GDF3, PDE5A, GALNTL6, OPMR1, and AOAH in thyroid cancer is associated with shortened survival; high expressions of NR2C1, FN1, IPCEF1, and ELMO1 is associated with prolonged survival. Among the genes associated with the prognosis of liver cancer, the genes associated with shorter survival period are AGO2, DCPS, IFIT5, LARP1, NCBP2, NUDT10, and NUDT16; the genes associated with longevity are EIF4E3, EIF4G3, METTL1, NCBP1, NSUN2, NUDT11, NUDT4, and WDR4. Depending on the prognostic role of genes in different cancers, they can influence patients to achieve the effect of reducing patients' symptoms. In the process of disease analysis of cancer patients, this paper uses bioinformation technology and Internet of things technology to promote the development of medical intelligence.

Effect of a modified regimen on drug-sensitive retreated pulmonary tuberculosis: A multicenter study in China.

Background and objective: Retreatment pulmonary tuberculosis (PTB) still accounts for a large proportion of tuberculosis, and the treatment outcome is unfavorable. The recurrence of retreatment PTB based on long-term follow-up has not been well demonstrated. This study aimed to evaluate effect of a modified regimen on drug-sensitive retreated pulmonary tuberculosis. Methods: This multicenter cohort study was conducted in 29 hospitals from 23 regions of China from July 1, 2009, to December 31, 2020. Patients were divided into two treatment regimen groups including experimental group [modified regimen (4H-Rt2-E-Z-S(Lfx)/4H-Rt2-E)]and control group [standard regimen (2H-R-E-Z-S/6H-R-E or 3H-R-E-Z/6H-R-E)]. The patients enrolled were followed up of 56 months after successful treatment. We compared the treatment success rate, treatment failure rate, adverse reaction rate, and recurrence rate between two regimens. Multivariate Cox regression model was used to identify the potential risk factors for recurrence after successful treatment with proportional hazards assumptions tested for all variables. Results: A total of 381 patients with retreatment PTB were enrolled, including 244 (64.0%) in the experimental group and 137 (36.0%) in the control group. Overall, the treatment success rate was significant higher in the experimental group than control group (84.0 vs. 74.5%, P = 0.024); no difference was observed in adverse reactions between the two groups (25.8 vs. 21.2%, P > 0.05). A total of 307 patients completed the 56 months of follow-up, including 205 with the modified regimen and 102 with the standard regimen. Among these, 10 cases (3.3%) relapsed, including 3 in the experimental group and 7 in the control group (1.5% vs 6.9%, P = 0.035). Reduced risks of recurrence were observed in patients treated with the modified regimen compared with the standard regimen, and the adjusted hazard ratio was 0.19 (0.04-0.77). Conclusion: The modified retreatment regimen had more favorable treatment effects, including higher treatment success rate and lower recurrence rate in patients with retreated drug-sensitive PTB.

Synthesis, Crystal Structure, and Characterization of Energetic Salts Based on 3,5-Diamino-4H-Pyrazol-4-One Oxime.

In order to broaden the study of energetic cations, a cation 3,5-diamino-4H-pyrazol-4-one oxime (DAPO) with good thermal stability was proposed, and its three salts were synthesized by a simple and efficient method. The structures of the three salts were verified by infrared spectroscopy, mass spectrometry, elemental analysis, and single crystal X-ray diffraction. The thermal stabilities of the three salts were verified by differential scanning calorimetry and thermos-gravimetric analysis. DAPO-based energetic salts are analysed using a variety of theoretical techniques, such as 2D fingerprint, Hirshfeld surface, and non-covalent interaction. Among them, the energy properties of perchlorate (DAPOP) and picrate (DAPOT) were determined by EXPLO5 program combined with the measured density and enthalpy of formation. These compounds have high density, acceptable detonation performance, good thermal stability, and satisfactory sensitivity. The intermolecular interactions of the four compounds were studied by Hirshfeld surface and non-covalent interactions, indicating that hydrogen bonds and π-π stacking interactions are the reasons for the extracellular properties of perchlorate (DAPOP) and picrate (DAPOT), indicating that DAPO is an optional nitrogen-rich cation for the design and synthesis of novel energetic materials with excellent properties.

More severe lung lesions in smoker patients with active pulmonary tuberculosis were associated with peripheral NK cell subsets.

BACKGROUND: Both pulmonary tuberculosis (PTB) and cigarette smoke (CS) exposure may lead to lung damage. The potential impact of CS exposure on tuberculosis-associated lung damage and the disturbance of immune cells and mediators involved, need to be further elucidated. METHODS: We firstly evaluated the chest X-ray (CXR) scores of a retrospective cohort of male patients with active PTB, followed for 6 months, and compared the scores between smoker (≥10 pack-years) and non-smoker patients. In a cross-sectional study, we measured the peripheral blood NK cell subsets and plasma inflammatory cytokines in male smoker and non-smoker patients with active PTB before anti-tuberculosis therapy, and the proportions of NK cell subsets and the levels of cytokines were analyzed for correlation with the CXR scores. RESULTS: In the retrospective cohort, male smoker patients with active PTB showed a higher CXR score, characterized by more cavitary lesions, enlarged lymph nodes and emphysema, as compared to non-smokers. The cross-sectional study revealed that the CXR score in smoker patients was correlated inversely with the percentages of blood CD107a+, NKP46+, and TIGIT+ NK cells. CONCLUSION: In patients with active PTB, CS exposure was associated with more severe lung lesions, which were correlated with peripheral NK cell subsets.

Hydroxytyrosol improves strenuous exercise-associated cardiac pathological changes via modulation of mitochondrial homeostasis.

Strenuous exercise is reported to provoke deleterious consequences including cardiac impairments, while the detailed mechanisms and effective interventions remain limited. The current study aims to explore the profitable effects of hydroxytyrosol (HT), one of the most abundant polyphenols derived from olive oil, on strenuous exercise-induced pathological changes in the heart and its underlying mechanisms. Sprague-Dawley male rats at the age of 8-week-old were supplemented with 25 mg kg-1 day-1 of HT 45 min before the beginning of strenuous exercise for a total of 8 weeks. HT treatment obviously improved the heart weight and morphology with lowered serum cardiac hypertrophy markers as well as cardiac oxidative stress. Moreover, the down-regulated mitochondrial biogenesis pathway, impaired mitochondrial complex activity, dysregulated expression of mitochondrial dynamics-related proteins and activated apoptotic pathway induced by Exe were all improved by HT. In vitro, 10 µM HT effectively reduced the reactive oxygen species level, promoted mitochondrial biogenesis, and inhibited apoptosis and cardiomyocyte hypertrophy in an angiotensin II-induced cardiomyocyte hypertrophy model. In addition, knockdown of the peroxisome proliferator-activated receptor gamma coactivator-1 alpha, the key regulator of mitochondrial biogenesis, partially abolished the benefits of HT. Our results demonstrate that the disturbance of mitochondrial homeostasis plays a substantial role in strenuous exercise-induced pathological cardiac hypertrophy, and HT presents as an effective intervention strategy targeting mitochondrial homeostasis for cardiac health.