Effects of Rifampicin Plus Levofloxacin or Isoniazid on Immune Function of Patients with Pulmonary Tuberculosis.

Context: Due to the different effects of various drugs and the lack of authoritative and unified guidelines in clinical practice, the choice of therapeutic drugs for pulmonary tuberculosis (TB) remains controversial. Rifampicin, levofloxacin, and isoniazid are all anti-TB drugs. However, no comparative studies of the treatment effects of rifampicin + levofloxacin and rifampicin + isoniazid have occurred. Objective: The study intended to analyze the therapeutic effects of rifampicin + levofloxacin compared to rifampicin + isoniazid in the treatment of pulmonary TB to provide a clinical reference, which could provide new references for future clinical treatment of the disease. Design: The research team conducted a prospective controlled study. Setting: The study took place at Zibo Zhoucun District People's Hospital in Zibo, China. Participants: Participants were 100 patients with pulmonary TB admitted to the hospital between March 2021 and December 2022. Interventions: The research team assigned participants to one of two groups: (1) the intervention group, with 56 participants who received rifampicin + levofloxacin therapy, and (2) the control group, with 44 participants who received rifampicin + isoniazid. Outcome Measures: The research team measured: (1) clinical efficacy, (2) incidence of adverse reactions, (3) changes in inflammatory factors, (4) changes in immunoglobulins (Igs), and (5) changes in T lymphocyte subsets. Results: The intervention group's total effective rate for treatment was significantly higher than that of the control group (P = .049). However, no significant difference existed between the groups in the incidence of adverse reactions (P > .05). Postintervention, the intervention group's inflammatory factors-IL-6, TNF-α, hs-CRP, and ß-EP-were significantly lower and its immunoglobulins (Igs) G/A/M (IgG/A/M) were significantly higher than those of the control group (P < .05). In addition, the intervention group's T lymphocyte subpopulations of CD3+ and CD4+ and CD4+/CD8+ were significantly higher and CD8+ was significantly lower than those in the control group (P < .05). In other words, the intervention group had a better immune function. Conclusions: Compared with rifampicin + isoniazid, rifampicin + levofloxacin had a better clinical effect in the treatment of pulmonary TB and could effectively regulate patients' immune functions and inhibit inflammatory reactions. The current research team recommends that rifampicin + levofloxacin become the preferred treatment for pulmonary TB in the absence of a drug allergy.

Erzhiwan Ameliorates Restraint Stress- and Monobenzone-Induced Depigmentation in Mice by Inhibiting Macrophage Migration Inhibitory Factor and 8-Hydroxy-2-Deoxyguanosine.

Purpose: Vitiligo is an autoimmune disease that results in the loss of epidermal melanocytes. The treatments for patients with vitiligo remain lacking. Erzhiwan (EZW), a traditional Chinese Medicine composed of Ligustri Lucidi Fructus and Ecliptae Herba, was used to ameliorate depigmentation since ancient China. This study aims to investigate the effect of EZW on vitiligo-related depigmentation. Methods: A vitiligo-related depigmentation mouse model was induced by monobenzone and restraint stress. The experimental depigmentation mice were treated with EZW. Histological observation of skin was conducted. Cutaneous oxidative damage and inflammation were determined. A network pharmacology analysis was carried out. Results: EZW reduced depigmentation score (p<0.01), cutaneous inflammatory infiltration (p<0.01), and CD8α-positive expression (p<0.01), and increased cutaneous melanin content in experimental depigmentation mice. EZW reduced stress reaction in experimental depigmentation mice (p<0.01). EZW inhibited 8-hydroxy-2-deoxyguanosine (8-OHdG)-related DNA oxidative damage in the skin (p<0.05, p<0.01). In addition, EZW reduced cutaneous macrophage migration inhibitory factor (MIF)-CD74-NF-κB signaling (p<0.01). The network pharmacology analysis demonstrated that EZW regulated necroptosis, apoptosis, and FoxO signaling pathways in vitiligo. An in vitro experiment showed that the main ingredient of EZW, specnuezhenide, protected against monobenzone and MIF-induced cell death in HaCaT cells (p<0.01). Conclusion: EZW ameliorates restraint stress- and monobenzone-induced depigmentation via the inhibition of MIF and 8-OHdG signaling. The findings provide a data basis of an utilization of EZW in vitiligo.

Identification of P450 Candidates Associated with the Biosynthesis of Physalin-Class Compounds in Physalis angulata.

The Physalis genus has long been used as traditional medicine in the treatment of various diseases. Physalins, the characteristic class of compounds in this genus, are major bioactive constituents. To date, the biogenesis of physalins remains largely unknown, except for the recently established knowledge that 24-methyldesmosterol is a precursor of physalin. To identify the genes encoding P450s that are putatively involved in converting 24-methyldesmosterol to physalins, a total of 306 P450-encoding unigenes were retrieved from our recently constructed P. angulata transcriptome. Extensive phylogenetic analysis proposed 21 P450s that might participate in physalin biosynthesis. To validate the candidates, we developed a virus-induced gene silencing (VIGS) system for P. angulata, and four P450 candidates were selected for the VIGS experiments. The reduction in the transcripts of the four P450 candidates by VIGS all led to decreased levels of physalin-class compounds in the P. angulata leaves. Thus, this study provides a number of P450 candidates that are likely associated with the biosynthesis of physalin-class compounds, forming a strong basis to reveal the unknown physalin biosynthetic pathway in the future.

Triad3A-Mediated K48-Linked ubiquitination and degradation of TLR9 impairs mitochondrial bioenergetics and exacerbates diabetic cardiomyopathy.

INTRODUCTION: Targeted protein degradation represents a promising therapeutic approach, while diabetic cardiomyopathy (DCM) arises as a consequence of aberrant insulin secretion and impaired glucose and lipid metabolism in the heart.. OBJECTIVES: Considering that the Toll-like receptor 9 (TLR9) signaling pathway plays a pivotal role in regulating energy metabolism, safeguarding cardiomyocytes, and influencing glucose uptake, the primary objective of this study was to investigate the impact of TLR9 on diabetic cardiomyopathy (DCM) and elucidate its underlying mechanism. METHODS: Mouse model of DCM was established using intraperitoneal injection of STZ, and mice were transfected with adeno-associated virus serotype 9-TLR9 (AAV9-TLR9) to assess the role of TLR9 in DCM. To explore the mechanism of TLR9 in regulating DCM disease progression, we conducted interactome analysis and employed multiple molecular approaches. RESULTS: Our study revealed a significant correlation between TLR9 expression and mouse DCM. TLR9 overexpression markedly mitigated cardiac dysfunction, myocardial fibrosis, oxidative stress, and apoptosis in DCM, while inflammation levels remained relatively unaffected. Mechanistically, TLR9 overexpression positively modulated mitochondrial bioenergetics and activated the AMPK-PGC1a signaling pathway. Furthermore, we identified Triad3A as an interacting protein that facilitated TLR9's proteasomal degradation through K48-linked ubiquitination. Inhibiting Triad3A expression improved cardiac function and pathological changes in DCM by enhancing TLR9 activity. CONCLUSIONS: The findings of this study highlight the critical role of TLR9 in maintaining cardiac function and mitigating pathological alterations in diabetic cardiomyopathy. Triad3A-mediated regulation of TLR9 expression and function has significant implications for understanding the pathogenesis of DCM. Targeting TLR9 and its interactions with Triad3A may hold promise for the development of novel therapeutic strategies for diabetic cardiomyopathy. Further research is warranted to fully explore the therapeutic potential of TLR9 modulation in the context of cardiovascular diseases.

Salidroside ameliorates pathological cardiac hypertrophy via TLR4-TAK1-dependent signaling.

Salidroside, a prominent active ingredient in traditional Chinese medicines, is garnering increased attention because of its unique pharmacological effects against ischemic heart disease via MAPK signaling, which plays a critical role in regulating the evolution of ventricular hypertrophy. However, the function of Salidroside on myocardial hypertrophy has not yet been elucidated. C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with Salidroside (100 mg kg-1  day-1 ) by oral gavage for 3 weeks starting 1 week after surgery. Four weeks after TAC surgery, the mice were subjected to echocardiography and then sacrificed to harvest the hearts for analysis. For in vitro study, neonatal rat cardiomyocytes were used to validate the protective effects of Salidroside in response to Angiotensin II (Ang II, 1 µM) stimulation. Here, we proved that Salidroside dramatically inhibited hypertrophic reactions generated by pressure overload and isoproterenol (ISO) injection. Salidroside prevented the activation of the TAK1-JNK/p38 axis. Salidroside pretreatment of TAK1-inhibited cardiomyocytes shows no additional attenuation of Ang II-induced cardiomyocytes hypertrophy and signaling pathway activation. The overexpression of constitutively active TAK1 removed the protective effects of Salidroside on myocardial hypertrophy. TAC-induced increase of TLR4 protein expression was reduced considerably in the Salidroside treated mice. Transient transfection of small interfering RNA targeting TLR4 (siTLR4) in cardiomyocytes did not further decrease the activation of the TAK1/JNK-p38 axis. In conclusion, Salidroside functioned as a TLR4 inhibitor and displayed anti-hypertrophic action via the TAK1/JNK-p38 pathway.

Metagenomic Analysis of Antibiotic Resistance Genes in Untreated Wastewater From Three Different Hospitals.

Controlling antibiotic resistance genes (ARGs) is a worldwide intervention to ensure global health. Hospital wastewater is the main pollution source of antibiotic-resistant bacteria and ARGs in the environment. Expanding our knowledge on the bacterial composition of hospital wastewater could help us to control infections in hospitals and decrease pathogen release into the environment. In this study, a high-throughput sequencing-based metagenomic approach was applied to investigate the community composition of bacteria and ARGs in untreated wastewater from three different types of hospitals [the general hospital, traditional Chinese medicine (TCM) hospital, and stomatology hospital]. In total, 130 phyla and 2,554 genera were identified from the microbiota of the wastewaters, with significantly different bacterial community compositions among the three hospitals. Total ARG analysis using the Antibiotic Resistance Genes Database (ARDB) and Comprehensive Antibiotic Resistance Database (CARD) revealed that the microbiota in the wastewaters from the three hospitals harbored different types and percentage of ARGs, and their composition was specific to the hospital type based on the correlation analysis between species and ARG abundance, some ARGs contributed to different bacterial genera with various relationships in different hospitals. In summary, our findings demonstrated a widespread occurrence of ARGs and ARG-harboring microbiota in untreated wastewaters of different hospitals, suggesting that protection measures should be applied to prevent human infections. Concurrently, hospital wastewater should be treated more specifically for the removal of pathogens before its discharge into the urban sewage system.

6-Gingerol protects against cardiac remodeling by inhibiting the p38 mitogen-activated protein kinase pathway.

6-Gingerol, a pungent ingredient of ginger, has been reported to possess anti-inflammatory and antioxidant activities, but the effect of 6-gingerol on pressure overload-induced cardiac remodeling remains inconclusive. In this study, we investigated the effect of 6-gingerol on cardiac remodeling in in vivo and in vitro models, and to clarify the underlying mechanisms. C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with 6-gingerol (20 mg/kg, ig) three times a week (1 week in advance and continued until the end of the experiment). Four weeks after TAC surgery, the mice were subjected to echocardiography, and then sacrificed to harvest the hearts for analysis. For in vitro study, neonatal rat cardiomyocytes and cardiac fibroblasts were used to validate the protective effects of 6-gingerol in response to phenylephrine (PE) and transforming growth factor-ß (TGF-ß) challenge. We showed that 6-gingerol administration protected against pressure overload-induced cardiac hypertrophy, fibrosis, inflammation, and dysfunction in TAC mice. In the in vitro study, we showed that treatment with 6-gingerol (20 µM) blocked PE-induced-cardiomyocyte hypertrophy and TGF-ß-induced cardiac fibroblast activation. Furthermore, 6-gingerol treatment significantly decreased mitogen-activated protein kinase p38 (p38) phosphorylation in response to pressure overload in vivo and extracellular stimuli in vitro, which was upregulated in the absence of 6-gingerol treatment. Moreover, transfection with mitogen-activated protein kinase kinase 6 expressing adenoviruses (Ad-MKK6), which specifically activated p38, abolished the protective effects of 6-gingerol in both in vitro and in vivo models. In conclusion, 6-gingerol improves cardiac function and alleviates cardiac remodeling induced by pressure overload in a p38-dependent manner. The present study demonstrates that 6-gingerol is a promising agent for the intervention of pathological cardiac remodeling.

IMPERFECTIVE EXINE FORMATION (IEF) is required for exine formation and male fertility in Arabidopsis.

KEY MESSAGE: IEF, a novel plasma plasma membrane protein, is important for exine formation in Arabidopsis. Exine, an important part of pollen wall, is crucial for male fertility. The major component of exine is sporopollenin which are synthesized and secreted by tapetum. Although sporopollenin synthesis has been well studied, the transportation of it remains elusive. To understand it, we analyzed the gene expression pattern in tapetal microdissection data, and investigated the potential transporter genes that are putatively regulated by ABORTED MICROSPORES (AMS). Among these genes, we identified IMPERFECTIVE EXINE FORMATION (IEF) that is important for exine formation. Compared to the wild type, ief mutants exhibit severe male sterility and pollen abortion, suggesting IEF is crucial for pollen development and male fertility. Using both scanning and transmission electron microscopes, we showed that exine structure was not well defined in ief mutant. The transient expression of IEF-GFP driven by the 35S promoter indicated that IEF-GFP was localized in plasma membrane. Furthermore, AMS can specifically activate the expression of promoterIEF:LUC in vitro, which suggesting AMS regulates IEF for exine formation. The expression of ATP-BINDING CASSETTE TRANSPORTER G26 (AGCB26) was not affected in ief mutants. In addition, SEM and TEM data showed that the sporopollenin deposition is more defective in abcg26/ief-2 than that of in abcg26, which suggesting that IEF is involved in an independent sporopollenin transportation pathway. This work reveal a novel gene, IEF regulated by AMS that is essential for exine formation.

Are mindfulness and self-efficacy related to presenteeism among primary medical staff: A cross-sectional study.

OBJECTIVES: In ensuring public welfare with primary medical and health services, the primary medical staff faces new tasks. Increasing workload, and therefore degrees of stress and burnout, can influence job satisfaction and lead to presenteeism, which is defined as the appearance to be on the job but not actually working. The purpose of this study is to investigate the current working situation and the relationship between presenteeism and mindfulness of primary medical staff and determine the mediating effect of self-efficacy on this relationship. METHOD: A cross-sectional survey was performed with 580 primary medical staff from 9 hospitals in Shaanxi province, northwest China. Presenteeism, mindfulness, and self-efficacy were measured by using a general information questionnaire, the Five-Facet Mindfulness Questionnaire, the General Self-Efficacy Scale, and the Stanford Presenteeism Scale. Mediating effect was analyzed by a series of hierarchical multiple regressions. RESULTS: A high level of presenteeism was found among 47.4% of the study participants. Presenteeism was negatively correlated with mindfulness(r = -0.409, P < 0.001) and self-efficacy(r = -0.678, P < 0.001). A positive correlation was found between mindfulness and self-efficacy(r = 0.584, P < 0.001). When controlling for self-efficacy (ß = -0.018, P > 0.05), the association was insignificant between presenteeism and mindfulness. CONCLUSION: The results identified the effect of mindfulness on presenteeism of primary medical staff is realized through self-efficacy,which also suggested to enhance self-efficacy on center location when developing management strategies for mental health education or training among primary medical staff.

[Changes of ion absorption, distribution and essential oil components of flowering Schizonepeta tenuifolia under salt stress].

In this paper, a pot experiment using quartz sands was conducted to study the effects of different concentrations of NaCl (0, 25, 50, 75, 100 mmol·L⁻¹) on the ion absorption, distribution and essential oil components of flowering Schizonepeta tenuifolia. The results showed that as NaCl concentration increased, Na⁺ content of root, stem, leaf and flower increased significantly, and that of the aerial parts was in a higher level than in the root. Regarding the K⁺ content, it decreased in the root but increased in stem, leaf and flower. Some changes were detected in the Ca²âº content, but not significant on the whole. The value of K⁺/Na⁺ and Ca²âº/Na⁺ reduced as a result of increasing NaCl concentrations. The content of essential oil increased under medium salt treatment (50 mmol·L⁻¹ NaCl). However, the synthesis and accumulation of essential oil was inhibited by the serious salt treatment (100 mmol·L⁻¹ NaCl). Over 98% of the essential oil components were terpenes, in which pulegone and menthone were the most two abundant compounds. Varieties of essential oil components did not change significantly under salt stress but their relative proportions did. The transformation of pulegone to menthone was enhanced and the value of pulegone/menthone based on their relative contents decreased with NaCl concentration increasing. Consequently, menthone ranked the most abundant compound by replacing pulegone. Relative content of D-limonene increased under medium and serious salt stress, and that of ß-caryophyllene only increased under mild treatments. So our research could provide references for the standard cultivation on saline soil of S. tenuifolia.

Efficacy and Safety of Tripterygium Wilfordii Hook F on Psoriasis Vulgaris: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Psoriasis is a chronic autoimmune-mediated skin disease that is characterized by persistent localized erythematous scaly plaque. Tripterygium wilfordii Hook F (TwHF), a well-known Chinese medicine that has been used for centuries in China to treat immune diseases, inflammation, and tumor, is accompanied by a degree of toxic effects. Its clinical efficacy and safety on psoriasis are incompletely understood. AIM: To summarize evidence concerning the efficacy and safety of TwHF in treating psoriasis. Methods. EMBASE, Ovid MEDLINE, PubMed, Web of Science, Springer, Cochrane Library, CNKI, CBM, Wanfang, and VIP database were searched up to October 2017. The included literature was assessed and extracted by two independent reviewers. To enhance the available evidence, a systematic review was performed to examine all relevant published literature relating to randomized controlled trials (RCTs) of TwHF. Relative ratios (RRs) and 95% confidence intervals (CIs) were calculated, and a meta-analysis was conducted with RevMan 5.3 software. RESULTS: Twenty eligible RCTs with 1872 participants were included for systematic review and meta-analysis. Studies were assessed using the Cochrane risk of bias tool. The meta-analysis of add-on effect of TwHF conferred benefit for psoriasis: combination treatment with compound glycyrrhizin (four studies, OR = 0.34, 95% CI 0.22-0.52, P < 0.00001, I2 = 0%), combination treatment with acitretin (three studies, OR = 0.25, 95% CI 0.10-0.63, P = 0.003, I2 = 50%), and combination treatment with compound amino-polypeptide tablet (three studies, OR = 0.37, 95% CI 0.22-0.63, P = 0.0002, I2 = 0%). CONCLUSIONS: Despite several mild side effects of TwHF, there is evidence that TwHF is an effective therapy for psoriasis. However, the conclusions are limited by the small number of included trials. More well-designed RCTs with extensive follow-up periods are warranted to clarify the effects and safety of TwHF in treating psoriasis. TRIAL REGISTRATION: This review was registered in the International Prospective Register of Systematic Reviews (CRD42016041363).

Assessment of the Genetic Diversity of Different Job's Tears (Coix lacryma-jobi L.) Accessions and the Active Composition and Anticancer Effect of Its Seed Oil.

Job's tears (Coix lachryma-jobi L.) is an important crop used as food and herbal medicine in Asian countries. A drug made of Job's tears seed oil has been clinically applied to treat multiple cancers. In this study, the genetic diversity of Job's tears accessions and the fatty acid composition, triglyceride composition, and anti-proliferative effect of Job's tears seed oil were analyzed using morphological characteristics and ISSR markers, GC-MS, HPLC-ELSD, and the MTT method. ISSR analysis demonstrated low genetic diversity of Job's tears at the species level (h = 0.21, I = 0.33) and the accession level (h = 0.07, I = 0.10), and strong genetic differentiation (GST = 0.6702) among all accessions. It also clustered the 11 accessions into three cultivated clades corresponding with geographical locations and two evidently divergent wild clades. The grouping patterns based on morphological characteristics and chemical profiles were in accordance with those clustered by ISSR analysis. Significant differences in morphological characteristics, fatty acid composition, triglyceride composition, and inhibition rates of seed oil were detected among different accessions, which showed a highly significant positive correlation with genetic variation. These results suggest that the seed morphological characteristics, fatty acid composition, and triglyceride composition may be mainly attributed to genetic factors. The proportion of palmitic acid and linoleic acid to oleic acid displayed a highly significant positive correlation with the inhibition rates of Job's tears seed oil for T24 cells, and thus can be an important indicator for quality control for Job's tears.