Comparison of the cachexia index based on hand-grip strength (H-CXI) with the original CXI for the prediction of cancer cachexia and prognosis in patients who underwent radical colectomy for colorectal cancer.

Background and aims: The cachexia index (CXI) is a novel biomarker for estimating cancer cachexia. The cachexia index based on hand-grip strength (H-CXI) has been recently developed as a simple proxy for CXI. The present study aims to compare both the H-CXI and CXI for the prediction of cancer cachexia and postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. Methods: Patients who underwent radical operations for colorectal cancer were included in this study. Cancer cachexia was diagnosed according to the international consensus outlined by Fearon et al. The cachexia index (CXI) was calculated as [skeletal muscle index (SMI) × serum albumin/neutrophil-to-lymphocyte ratio (NLR)]. The H-CXI was calculated as [hand-grip strength (HGS)/height2 × serum albumin/NLR]. The SMI was measured based on the preoperative CT images at the third lumbar vertebra (L3) level. HGS was measured before surgery. Results: From July 2014 to May 2021, a total of 1,411 patients were included in the present study, of whom 361 (25.6%) were identified as having cancer cachexia. Patients with cachexia had a lower CXI (p < 0.001) and lower H-CXI (p < 0.001) than those without cachexia. A low CXI but not low H-CXI independently predicted cancer cachexia in the multivariate analysis (OR 1.448, p = 0.024). Both a low CXI (HR 1.476, p < 0.001 for OS; HR 1.611, p < 0.001 for DFS) and low H-CXI (HR 1.369, p = 0.007 for OS; HR 1.642, p < 0.001 for DFS) were independent predictors for overall survival (OS) and disease-free survival (DFS) after adjusting for the same covariates. A low H-CXI but not low CXI was an independent risk factor for postoperative complications (OR 1.337, p = 0.044). No significant association was found between cancer cachexia and postoperative complications. Conclusion: The CXI and H-CXI exhibited better prognostic value than cancer cachexia for the prediction of postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. The H-CXI was a superior index over the CXI in predicting short-term clinical outcomes, whereas the CXI demonstrated a closer correlation with Fearon's criteria for cancer cachexia. Ideal tools for the assessment of cancer cachexia should incorporate not only weight loss but also muscle mass, physical function, and inflammatory state.

Prognostic value of GLIM-defined malnutrition in combination with hand-grip strength or gait speed for the prediction of postoperative outcomes in gastric cancer patients with cachexia.

BACKGROUND: Cancer cachexia is associated with impaired functional and nutritional status and worse clinical outcomes. Global Leadership Initiative in Malnutrition (GLIM) consensus recommended the application of GLIM criteria to diagnose malnutrition in patients with cachexia. However, few previous study has applied the GLIM criteria in patients with cancer cachexia. METHODS: From July 2014 to May 2019, patients who were diagnosed with cancer cachexia and underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index was measured using abdominal computed tomography (CT) images at the third lumbar vertebra (L3) level. Hand-grip strength and 6-meters gait speed were measured before surgery. RESULTS: A total of 356 patients with cancer cachexia were included in the present study, in which 269 (75.56%) were identified as having malnutrition based on the GLIM criteria. GLIM-defined malnutrition alone did not show significant association with short-term postoperative outcomes, including complications, costs or length of postoperative hospital stays. The combination of low hand-grip strength or low gait speed with GLIM-defined malnutrition led to a significant predictive value for these outcomes. Moreover, low hand-grip strength plus GLIM-defined malnutrition was independently associated with postoperative complications (OR 1.912, 95% CI 1.151-3.178, P = 0.012). GLIM-defined malnutrition was an independent predictive factor for worse OS (HR 2.310, 95% CI 1.421-3.754, P = 0.001) and DFS (HR 1.815, 95% CI 1.186-2.779, P = 0.006) after surgery. The addition of low hand-grip strength or low gait speed to GLIM-defined malnutrition did not increase its predictive value for survival. CONCLUSION: GLIM-defined malnutrition predicted worse long-term survival in gastric cancer patients with cachexia. Gait speed and hand-grip strength added prognostic value to GLIM-defined malnutrition for the prediction of short-term postoperative outcomes, which could be incorporated into preoperative assessment protocols in patients with cancer cachexia.

Comparisons of Drug-Eluting Balloon versus Drug-Eluting Stent in the Treatment of Young Patients with Acute Myocardial Infarction.

BACKGROUND: The incidence of acute myocardial infarction (AMI) in the younger population has been increasing gradually in recent years. The objective of the present study is to investigate the safety and effectiveness of drug-eluting balloons (DEBs) in young patients with AMI. METHODS: All consecutive patients with AMI aged ≤ 45 years were retrospectively enrolled. The primary endpoint was a device-oriented composite endpoint (DOCE) of cardiac death, target vessel myocardial infarction (MI), or target lesion revascularization (TLR). The secondary study endpoints included heart failure and major bleeding events. RESULTS: A total of 276 young patients presenting with AMI were finally included. The median follow-up period was 1155 days. Patients treated with DEBs had a trend toward a lower incidence of DOCEs (3.0% vs. 11.0%, p = 0.12) mainly driven by the need for TLR (3.0% vs. 9.1%, p = 0.19) than those treated with DESs. No significant differences between the two groups were detected in the occurrence of cardiac death (0.0% vs. 0.5%, p = 0.69), MI (0.0% vs. 1.4%, p = 0.40), heart failure (0.0% vs. 1.9%, p = 0.39), or major bleeding events (1.5% vs 4.8%, p = 0.30). Multivariate regression analysis showed that DEBs were associated with a trend toward a lower risk of DOCEs (HR 0.13, 95% CI [0.02, 1.05], p = 0.06). CONCLUSIONS: The findings of the present study suggested that DEBs might be a potential treatment option in young patients with AMI. A larger scale, randomized, multicenter study is required to investigate the safety and effectiveness of DEBs in this setting.

A Novel Reperfusion Strategy for Primary Percutaneous Coronary Intervention in Patients with Acute ST-Segment Elevation Myocardial Infarction: A Prospective Case Series.

BACKGROUND: Ischemia reperfusion injury (IRI) remains a major problem in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). We have developed a novel reperfusion strategy for PCI and named it "volume-controlled reperfusion (VCR)". The aim of the current study was to assess the safety and feasibility of VCR in patients with STEMI. METHODS: Consecutive patients admitted to Beijing Chaoyang Hospital with STEMI were prospectively enrolled. The feasibility endpoint was procedural success. The safety endpoints included death from all causes, major vascular complications, and major adverse cardiac event (MACE), i.e., a composite of cardiac death, myocardial reinfarction, target vessel revascularization (TVR), and heart failure. RESULTS: A total of 30 patients were finally included. Procedural success was achieved in 28 (93.3%) patients. No patients died during the study and no major vascular complications or MACE occurred during hospitalization. With the exception of one patient (3.3%) who underwent TVR three months after discharge, no patient encountered death (0.0%), major vascular complications (0.0%), or and other MACEs (0.0%) during the median follow-up of 16 months. CONCLUSION: The findings of the pilot study suggest that VCR has favorable feasibility and safety in patients with STEMI. Further larger randomized trials are required to evaluate the effectiveness of VCR in STEMI patients.

Holistic review and meta-analysis of independent impact of the residual SYNTAX score on prognosis in patients with acute coronary syndrome.

Objectives. The appropriate extent of revascularization following primary intervention is unknown. We conducted a systematic review and meta-analysis of residual Syntax score (rSS) to predict the outcomes and provide guide to optimal management of revascularization following primary intervention. Designs. Previously published studies from 2007 to 2020 assessing the prognostic impact of rSS after ACS were included for this meta-analysis. The primary endpoint was defined as the major adverse clinical events (MACE) in multivariable analysis. The risk ratios (RRs) with 95% confidence intervals (CI) were calculated using the RevMan 5.4 software. Results. A total of 8,157 participants complicated with ACS from 12 clinical studies were included in this analysis. Based on the wide range of rSS studies available, we classified it into two major groups: rSS < 8 and rSS ≥ 8. In multivariate analysis, the rSS was an independent risk marker for MACE [RR = 1.04 (95%CI; 1.00-1.08)], all-cause mortality [RR = 1.05 (1.03-1.07)] and cardiovascular death [RR = 1.05 (1.03-1.07)]. Patients with incomplete revascularization (ICR) showed higher prevalence of MACE along with all-cause mortality, cardiovascular morality, and recurrent myocardial infarction without significant heterogeneity [RR = 1.60 (1.03-1.07), 2.30 (1.57-3.38), 3.57 (2.09-6.10) and 1.70 (1.38-2.09), respectively]. The patients with rSS ≥ 8 presented higher frequency of all-cause mortality [RR = 2.99 (2.18-4.09)], cardiovascular death [RR = 3.32 (2.22-4.95)], and recurrent myocardial infarction [RR = 1.64 (1.34-2.02)]. Conclusion. The meta-analysis indicated that an rSS value of 8 could be a reasonable cut-off for incomplete revascularization after ACS and is an efficient tool to guide revascularization. In future, detailed research should focus on investigation of the optimal value of the rSS score.

The zebrafish NLRP3 inflammasome has functional roles in ASC-dependent interleukin-1ß maturation and gasdermin E-mediated pyroptosis.

The NLR family pyrin domain containing 3 (NLRP3) inflammasome is one of the best-characterized inflammasomes in humans and other mammals. However, knowledge about the NLRP3 inflammasome in nonmammalian species remains limited. Here, we report the molecular and functional identification of an NLRP3 homolog (DrNLRP3) in a zebrafish (Danio rerio) model. We found that DrNLRP3's overall structural architecture was shared with mammalian NLRP3s. It initiates a classical inflammasome assembly for zebrafish inflammatory caspase (DrCaspase-A/-B) activation and interleukin 1ß (DrIL-1ß) maturation in an apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC)-dependent manner, in which DrNLRP3 organizes DrASC into a filament that recruits DrCaspase-A/-B by homotypic pyrin domain (PYD)-PYD interactions. DrCaspase-A/-B activation in the DrNLRP3 inflammasome occurred in two steps, with DrCaspase-A being activated first and DrCaspase-B second. DrNLRP3 also directly activated full-length DrCaspase-B and elicited cell pyroptosis in a gasdermin E (GSDME)-dependent but ASC-independent manner. These two events were tightly coordinated by DrNLRP3 to ensure efficient IL-1ß secretion for the initiation of host innate immunity. By knocking down DrNLRP3 in zebrafish embryos and generating a DrASC-knockout (DrASC-/-) fish clone, we characterized the function of the DrNLRP3 inflammasome in anti-bacterial immunity in vivo The results of our study disclosed the origin of the NLRP3 inflammasome in teleost fish, providing a cross-species understanding of the evolutionary history of inflammasomes. Our findings also indicate that the NLRP3 inflammasome may coordinate inflammatory cytokine processing and secretion through a GSDME-mediated pyroptotic pathway, uncovering a previously unrecognized regulatory function of NLRP3 in both inflammation and cell pyroptosis.

The Interplay Between Pattern Recognition Receptors and Autophagy in Inflammation.

Pattern recognition receptors (PRRs) are sensors of exogenous and endogenous "danger" signals from pathogen-associated molecular patterns (PAMPs), and damage associated molecular patterns (DAMPs), while autophagy can respond to these signals to control homeostasis. Almost all PRRs can induce autophagy directly or indirectly. Toll-like receptors (TLRs), Nod-like receptors (NLRs), retinoic acid-inducible gene-I-like receptors (RLRs), and cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway can induce autophagy directly through Beclin-1 or LC3-dependent pathway, while the interactions with the receptor for advanced glycation end products (RAGE)/high mobility group box 1 (HMGB1), CD91/Calreticulin, and TLRs/HSPs are achieved by protein, Ca2+, and mitochondrial homeostasis. Autophagy presents antigens to PRRs and helps to clean the pathogens. In addition, the induced autophagy can form a negative feedback regulation of PRRs-mediated inflammation in cell/disease-specific manner to maintain homeostasis and prevent excessive inflammation. Understanding the interaction between PRRs and autophagy in a specific disease will promote drug development for immunotherapy. Here, we focus on the interactions between PRRs and autophagy and how they affect the inflammatory response.

BTLA-HVEM Checkpoint Axis Regulates Hepatic Homeostasis and Inflammation in a ConA-Induced Hepatitis Model in Zebrafish.

The BTLA-HVEM checkpoint axis plays extensive roles in immunomodulation and diseases, including cancer and autoimmune disorders. However, the functions of this checkpoint axis in hepatitis remain limited. In this study, we explored the regulatory role of the Btla-Hvem axis in a ConA-induced hepatitis model in zebrafish. Results showed that Btla and Hvem were differentially expressed on intrahepatic Cd8+ T cells and hepatocytes. Knockdown of Btla or Hvem significantly promoted hepatic inflammation. Btla was highly expressed in Cd8+ T cells in healthy liver but was downregulated in inflamed liver, as evidenced by a disparate proportion of Cd8+Btla+ and Cd8+Btla- T cells in individuals without or with ConA stimulation. Cd8+Btla+ T cells showed minimal cytotoxicity to hepatocytes, whereas Cd8+Btla- T cells were strongly reactive. The depletion of Cd8+Btla- T cells reduced hepatitis, whereas their transfer enhanced hepatic inflammation. These observations indicate that Btla endowed Cd8+Btla+ T cells with self-tolerance, thereby preventing them from attacking hepatocytes. Btla downregulation deprived this tolerization. Mechanistically, Btla-Hvem interaction contributed to Cd8+Btla+ T cell tolerization, which was impaired by Hvem knockdown but rescued by soluble Hvem protein administration. Notably, Light was markedly upregulated on Cd8+Btla- T cells, accompanied by the transition of Cd8+Btla+Light- to Cd8+Btla-Light+ T cells during hepatitis, which could be modulated by Cd4+ T cells. Light blockade attenuated hepatitis, thereby suggesting the positive role of Light in hepatic inflammation. These findings provide insights into a previously unrecognized Btla-Hvem-Light regulatory network in hepatic homeostasis and inflammation, thus adding a new potential therapeutic intervention for hepatitis.

Characterization of an NLRP1 Inflammasome from Zebrafish Reveals a Unique Sequential Activation Mechanism Underlying Inflammatory Caspases in Ancient Vertebrates.

NLRP1 inflammasome is one of the best-characterized inflammasomes in humans and other mammals. However, the existence of this inflammasome in nonmammalian species remains poorly understood. In this study, we report the molecular and functional identification of an NLRP1 homolog, Danio rerio NLRP1 (DrNLRP1) from a zebrafish (D. rerio) model. This DrNLRP1 possesses similar structural architecture to mammalian NLRP1s. It can trigger the formation of a classical inflammasome for the activation of zebrafish inflammatory caspases (D. rerio Caspase [DrCaspase]-A and DrCaspase-B) and maturation of D. rerio IL-1ß in a D. rerio ASC (DrASC)-dependent manner. In this process, DrNLRP1 promotes the aggregation of DrASC into a filament with DrASCCARD core and DrASCPYD cluster. The assembly of DrNLRP1 inflammasome depends on the CARD-CARD homotypic interaction between DrNLRP1 and DrASCCARD core, and PYD-PYD interaction between DrCaspase-A/B and DrASCPYD cluster. The FIIND domain in DrNLRP1 is necessary for inflammasome assembly. To understand the mechanism of how the two DrCaspases are coordinated in DrNLRP1 inflammasome, we propose a two-step sequential activation model. In this model, the recruitment and activation of DrCaspase-A/B in the inflammasome is shown in an alternate manner, with a preference for DrCaspase-A followed by a subsequent selection for DrCaspase-B. By using morpholino oligonucleotide-based knockdown assays, the DrNLRP1 inflammasome was verified to play important functional roles in antibacterial innate immunity in vivo. These observations demonstrate that the NLRP1 inflammasome originated as early as in teleost fish. This finding not only gives insights into the evolutionary history of inflammasomes but also provides a favorable animal model for the study of NLRP1 inflammasome-mediated immunology and diseases.

Identification of DEAD-Box RNA Helicase DDX41 as a Trafficking Protein That Involves in Multiple Innate Immune Signaling Pathways in a Zebrafish Model.

DDX41 is an important sensor for host recognition of DNA viruses and initiation of nuclear factor-κB (NF-κB) and IFN signaling pathways in mammals. However, its occurrence and functions in other vertebrates remain poorly defined. Here, a DDX41 ortholog [Danio rerio DDX41 (DrDDX41)] with various conserved structural features to its mammalian counterparts was identified from a zebrafish model. This DrDDX41 was found to be a trafficking protein distributed in the nucleus of resting cells but transported into the cytoplasm under DNA stimulation. Two nuclear localization signal motifs were localized beside the coiled-coil domain, whereas one nuclear export signal motif existed in the DEADc domain. DrDDX41 acts as an initiator for the activation of NF-κB and IFN signaling pathways in a Danio rerio STING (DrSTING)-dependent manner through its DEADc domain, which is a typical performance of mammalian DDX41. These observations suggested the conservation of DDX41 proteins throughout the vertebrate evolution, making zebrafish an alternative model in understanding DDX41-mediated immunology. With this model system, we found that DrDDX41 contributes to DrSTING-Danio rerio STAT6 (DrSTAT6)-mediated chemokine (Danio rerio CCL20) production through its DEADc domain. To the best of our knowledge, this work is the first report showing that DDX41 is an upstream initiator in this newly identified signaling pathway. The DrDDX41-mediated signaling pathways play important roles in innate antibacterial immunity because knockdown of either DrDDX41 or DrSTING/DrSTAT6 significantly reduced the survival of zebrafish under Aeromonas hydrophilia or Edwardsiella tarda infection. Our findings would enrich the current knowledge of DDX41-mediated immunology and the evolutionary history of the DDX41 family.

Peroxiredoxin 1 (Prx1) is a dual-function enzyme by possessing Cys-independent catalase-like activity.

Peroxiredoxin (Prx) was previously known as a Cys-dependent thioredoxin. However, we unexpectedly observed that Prx1 from the green spotted puffer fish Tetraodon nigroviridis (TnPrx1) was able to reduce H2O2 in a manner independent of Cys peroxidation and reductants. This study aimed to validate a novel function for Prx1, delineate the biochemical features and explore its antioxidant role in cells. We have confirmed that Prx1 from the puffer fish and humans truly possesses a catalase (CAT)-like activity that is independent of Cys residues and reductants, but dependent on iron. We have identified that the GVL motif was essential to the CAT-like activity of Prx1, but not to the Cys-dependent thioredoxin peroxidase (POX) activity, and generated mutants lacking POX and/or CAT-like activities for individual functional validation. We discovered that the TnPrx1 POX and CAT-like activities possessed different kinetic features in the reduction of H2O2 The overexpression of wild-type TnPrx1 and mutants differentially regulated the intracellular levels of reactive oxygen species (ROS) and the phosphorylation of p38 in HEK-293T cells treated with H2O2 Prx1 is a dual-function enzyme by acting as POX and CAT with varied affinities towards ROS. This study extends our knowledge on Prx1 and provides new opportunities to further study the biological roles of this family of antioxidants.

Testosterone level and mortality in elderly men with systolic chronic heart failure.

Previous studies on the prognostic significance of serum levels of androgens in patients with chronic heart failure (CHF) have yielded conflicting results. The aim of this study was to examine the relationship between serum concentration of testosterone and mortality in men with systolic CHF. A total of 175 elderly men (age ≥ 60 years) with CHF were recruited. Total testosterone (TT) and sex hormone-binding globulin (SHBG) were measured, and estimated free testosterone (eFT) was calculated. The median follow-up time was 3.46 years. Of these patients, 17 had a TT level below 8 nmol l⁻¹ (230 ng dl⁻¹), 27 had an eFT level below 0.225 nmol l⁻¹ (65 pg ml⁻¹) and 12 had both. Using the age-specific tenth percentiles of TT and eFT in healthy men in our laboratory as cutoff points, the prevalences of TT and eFT deficiency was 21.7% (38/175) and 27.4% (48/175), respectively. Both TT and eFT were inversely associated with left ventricular ejection fraction (LVEF) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) (all P<0.01). Kaplan-Meier curves for patients in low, medium and high tertiles according to TT and eFT level showed significantly different cumulative survival rate (both P<0.01 by log-rank test). However, after adjustment for clinical variables, there were no significant associations of either TT or eFT levels with survival time (OR=0.97, 95% CI: 0.84-1.12, P=0.28 and OR=0.92, 95% CI: 0.82-1.06, P=0.14, respectively). Our study showed that levels of TT and eFT are commonly decreased in elderly patients with systolic CHF and related to disease severity, but they are not independent predictors for mortality.

Virtual Instrument for Determining Rate Constant of Second-Order Reaction by pX Based on LabVIEW 8.0.

The virtual instrument system based on LabVIEW 8.0 for ion analyzer which can measure and analyze ion concentrations in solution is developed and comprises homemade conditioning circuit, data acquiring board, and computer. It can calibrate slope, temperature, and positioning automatically. When applied to determine the reaction rate constant by pX, it achieved live acquiring, real-time displaying, automatical processing of testing data, generating the report of results; and other functions. This method simplifies the experimental operation greatly, avoids complicated procedures of manual processing data and personal error, and improves veracity and repeatability of the experiment results.

[Effects of earthworm (Eisennia foetida ) on As, P uptake by maize and As, P fractional transformation in the rhizosphere].

A pot experiment was conducted to examine the roles of earthworm in As uptake from original As-polluted soil by maize (Zea mays L.), and their effects on As, P fractions in the rhizosphere. The As-polluted soils with three As levels were collected from the arable soil near As mine. The plants were harvested after 10 weeks of growth. Dry weight (DW) and P, As concentrations of plants, as well as As and P fractions of the rhizospheric soil, were determined. The results showed that inoculated earthworm or appended rice straw increased maximal 149%, 222% DW of root and shoot, respectively. At the medium and high soil As levels, root As concentration in the soil treated by earthworm and rice straw was highest among all treatments, and earthworm increased more As concentration of shoot than rice straw did. In different soil As levels, root P concentration in the soil treated by earthworm was highest, and shoot P by rice straw. Ca-P affected maize absorbing As at the low soil As level(r = 0.981), and maize absorbing Al-P was restrained by As involved in well-crystallized hydrous oxides of Fe and Al at the medium (r = 0.953)and high (r = 0.997)soil As levels. The concentration of non-specially absorbed As and As combined with Fe or Al and of O-P increased at the soil inoculated earthworm or/and appended rice straw at the same time. These results indicated that earthworm was more valuable for plant developing than rice straw was.

[Symptomatic evaluation of late onset hypogonadism in healthy Chinese men].

OBJECTIVE: To investigate the correlation between the symptoms and serum levels of androgen in healthy Chinese men aged over 40 years, and to work out a new symptomatic inventory for screening late onset hypogonadism (LOH) in Chinese men. METHODS: An 18-item questionnaire was designed and 637 respondents were collected from Beijing, Shanghai, Xi'an and Chongqing. Serum total testosterone, calculated free testosterone, testosterone secretion index and free testosterone index were measured. An analysis of the correlation between symptoms and androgens was performed. RESULTS: The twelve-item symptoms were significantly correlated to 2 or more of the 4 androgens mentioned above, marking up a new symptomatic inventory for screening LOH, with a 70% sensitivity and 46% specificity. CONCLUSION: The new symptomatic inventory is acceptable for the screening purpose. The relatively low specificity may be related to the individual response to the decline of serum androgens and age-related changes of other hormones, such as GH-IGF-1 axis, DHEA, thyroid hormones, melatonin and leptin.

[Effects of tributyltin chloride (TBT) and triphenyltin chloride (TPT) on rat testicular Leydig cells].

OBJECTIVE: To investigate the effects of tributyltin chloride (TBT) and triphenyltin chloride (TPT) on rat testicular Leydig cells. METHODS: The rat Leydig cells (LC-540) were incubated with 0 to 80 nmol/L TBT and TPT for 24 to approximately 96 h, and then the cell viability was determined by MTT. DNA fragmentation ladder formation of cell apoptosis was examined by agarose electrophoresis. Effects of chelator of intracellular Ca2+ (BAPTA) and the inhibitors of PKA, PKC and TPK on cell apoptosis induced by TBT were observed. Effects of TBT on testosterone production in primary cultured rat Leydig cells treated with or without hCG were detected. RESULTS: TBT and TPT suppressed Leydig cell survival in a time- and dose-dependent manner. The suppressive effects of TBT and TPT on the cell survival was caused by apoptosis which was determined by DNA ladder formation. The apoptotic effect of TBT was possibly mediated by the rise in intracellular Ca2+ because it could be blocked by BAPTA, the chelator of intracellular Ca2+; PKA, PKC and TPK inhibitors did not prevent the apoptotic effects induced by TBT. TBT markedly suppressed testosterone production of primary cultured rat Leydig cells with or without hCG stimulation. CONCLUSION: TBT and TPT induced apoptosis in rat testicular Leydig cells possibly through increasing intracellular Ca2+. TBT reduced the testosterone production of rat Leydig cells.

[A comparative survey of sex hormones levels between elderly men with chronic heart failure and normal elderly subjects].

OBJECTIVE: To understand the sex hormone levels in elderly men with chronic heart failure and the relationship between sex hormone levels and heart function. METHODS: One hundred male patients diagnosed chronic heart failure clinically aged from 60 to 87 were selected in this study. All patients' left ventricular ejection fraction were less than 0.45. Four hundred elderly healthy men were studied as control. Blood samples were collected in the morning and TT, FT, DHEAS, SHBG, E(2), LH, FSH were measured. The results were compared with the hormone levels of healthy men with the same mean age. RESULTS: (1) In elderly men with chronic heart failure, the level of DHEAS was decreased with age (P < 0.05). However, the levels of SHBG, LH, FSH were increased with age (P < 0.05, P < 0.01). (2) Compared with healthy men the levels of TT, FT, E(2) and DHEAS were decreased significantly (P < 0.01) and the level of SHBG was significantly increased (P < 0.01). (3) The level of FT was positively correlated with LVEF (r = 0.279, P = 0.034). CONCLUSION: The androgen levels in elderly male patients with chronic heart failure were decreased significantly and the level of FT was negatively correlated with degree of heart failure.

Saturated free fatty acids, palmitic acid and stearic acid, induce apoptosis by stimulation of ceramide generation in rat testicular Leydig cell.

In men, obesity has generally been associated with reduced plasma testosterone levels and with elevation of the plasma free fatty acids (FFAs). In this study, we investigated the effects of saturated FFAs including palmitic acid (PA) and stearic acid (SA), and polyunsaturated FFA arachidonic acid (AA) on the survival of rat testicular Leydig cell cultured in vitro. PA and SA markedly suppressed Leydig cell survival in a time- and dose-dependent manner. In contrast, AA stimulated the cell proliferation at 5-10 times of physiological concentration. The suppressive effect of PA and SA on cell survival was caused by apoptosis evidenced by DNA ladder formation and Annexin V-EGFP/propidium iodide staining of the cells. The apoptotic effect of PA was possibly mediated by ceramide generation because it could be completely blocked by ceramide synthase inhibitor fumonisin B1 and exogenous ceramide itself could directly induce apoptosis in vitro. Surprisingly, the apoptosis induced by PA could be partly prevented by AA. These results indicate that PA and SA induce apoptosis in testicular Leydig cells by ceramide production and these apoptotic effects may be a possible mechanism for reproductive abnormalities in obese men, and AA can partly prevent the apoptotic effect induced by saturated FFA.