Androcin 18-1, a novel scorpion-venom peptide, shows a potent antitumor activity against human U87 cells via inducing mitochondrial dysfunction.

Scorpion venom is a potent natural source for antitumor drug development due to the multiple action modes of anticancer components. Although the sequence of Androcin 18-1 has been identified from the transcriptome profile of the scorpion venom Androctonus bicolor, its bioactivity remains unclear. In this study, we described the antitumor mechanism whereby Androcin 18-1 inhibits the proliferation and induces apoptosis by inducing cell membrane disruption, ROS accumulation, and mitochondrial dysfunction in human U87 glioblastoma cells. Moreover, Androcin 18-1 could suppress cell migration via the mechanisms associated with cytoskeleton disorganization and MMPs/TIMPs expression regulation. The discovery of this work highlights the potential application of Androcin 18-1 in drug development for glioblastoma treatment.

Association of dietary live microbe intake with frailty in US adults: evidence from NHANES.

OBJECTIVE: Diets rich in live microbes can bring various health benefits. However, the association between dietary live microbe intake and frailty has not been studied. METHODS: The study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. A total of 11,529 participants were included. Sanders et al. classified the level of live microbes in foods into low (<104 CFU/g), medium (104-107 CFU/g), or high (>107 CFU/g). With the methodology of Sanders et al. and dietary questionnaire data, participants were divided into three groups: (1) low dietary live microbe intake group (only low-level foods), (2) medium dietary live microbe intake group (medium but not high-level foods), and (3) high dietary live microbe intake group (any high-level foods). Additionally, foods with medium and high live microbe content were aggravated as MedHi. Frailty index ≥0.25 is defined as frailty. The weighted logistic regression analysis was conducted to examine the relationship between the intake of dietary live microbe and frailty. The restricted cubic splines (RCS) were employed to detect the nonlinear relationships. RESULTS: In the fully adjusted model, participants with high dietary intake of live microbe had a significantly lower risk of frailty than those with low dietary intake of live microbe (OR = 0.67, 95% CI: 0.56, 0.79). For every 100 grams of MedHi food consumed, the risk of frailty decreased by 11% (OR = 0.89, 95% CI: 0.85, 0.92) after adjusting all covariates. The RCS indicated the existence of non-linear relationships. For those who consumed less than 100 grams of MedHi, increasing MedHi intake may significantly reduce the risk of frailty, but after exceeding 100 grams, the curve gradually levels off. CONCLUSIONS: Our results suggested that increasing dietary live microbe intake was associated with a lower risk of frailty. However, more research is needed to verify this.

FS145, the first flea-derived disintegrin, inhibits angiogenesis through specifically binding integrin αvß3.

FS145, a protein containing a WGD motif, was previously described from the salivary transcriptome of the flea Xenopsylla cheopis. Nevertheless, its biological function and complete structure are still uncertain. Herein, FS145 was confirmed to adopt a common αßß structure with the WGD motif exposed on its surface and located right at the top of a loop composed of residues 72-81. Furthermore, FS145 dose-dependently inhibited the proliferation, adhesion, migration, and tube formation of HUVECs by not only binding to integrin αvß3 but also by subsequently inactivating the FAK/Src/MAPK pathway along with the reduction of the expression of MMP-2, MMP-9, VEGFA, bFGF, Ang2, Tie2, HIF-1α, and FAK. Moreover, FS145 also inhibited aortic vessel sprout and showed strong anti-angiogenic activities as assessed ex vivo, by employing the rat aortic ring assay, chick embryo chorioallantoic membrane, and zebrafish embryo models. Altogether, our results suggest that FS145 suppresses angiogenesis ex vivo and in vitro by blocking integrin αvß3. The current study reveals the first anti-angiogenesis disintegrin with WGD motif from invertebrates and provides a beneficial pharmacological activity to inhibit abnormal angiogenesis.

Cath-KP, a novel peptide derived from frog skin, prevents oxidative stress damage in a Parkinson's disease model.

Parkinson's disease (PD) is a neurodegenerative condition that results in dyskinesia, with oxidative stress playing a pivotal role in its progression. Antioxidant peptides may thus present therapeutic potential for PD. In this study, a novel cathelicidin peptide (Cath-KP; GCSGRFCNLFNNRRPGRLTLIHRPGGDKRTSTGLIYV) was identified from the skin of the Asiatic painted frog ( Kaloula pulchra). Structural analysis using circular dichroism and homology modeling revealed a unique αßß conformation for Cath-KP. In vitro experiments, including free radical scavenging and ferric-reducing antioxidant analyses, confirmed its antioxidant properties. Using the 1-methyl-4-phenylpyridinium ion (MPP +)-induced dopamine cell line and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice, Cath-KP was found to penetrate cells and reach deep brain tissues, resulting in improved MPP +-induced cell viability and reduced oxidative stress-induced damage by promoting antioxidant enzyme expression and alleviating mitochondrial and intracellular reactive oxygen species accumulation through Sirtuin-1 (Sirt1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway activation. Both focal adhesion kinase (FAK) and p38 were also identified as regulatory elements. In the MPTP-induced PD mice, Cath-KP administration increased the number of tyrosine hydroxylase (TH)-positive neurons, restored TH content, and ameliorated dyskinesia. To the best of our knowledge, this study is the first to report on a cathelicidin peptide demonstrating potent antioxidant and neuroprotective properties in a PD model by targeting oxidative stress. These findings expand the known functions of cathelicidins, and hold promise for the development of therapeutic agents for PD.

Peptide TK-HR from the Skin of Chinese Folk Medicine Frog Hoplobatrachus Rugulosus Accelerates Wound Healing via the Activation of the Neurokinin-1 Receptor.

Wound healing is a complex process and remains a considerable challenge in clinical trials due to the lack of ideal therapeutic drugs. Here, a new peptide TK-HR identified from the skin of the frog Hoplobatrachus rugulosus was tested for its ability to heal cutaneous wounds in mice. Topical application of TK-HR at doses of 50-200 µg/mL significantly accelerated wound closure without causing any adverse effects in the animals. In vitro and in vivo investigations proved the regulatory role of the peptide on neutrophils, macrophages, keratinocytes, and vein endothelial cells involved in the inflammatory, proliferative, and remodeling phases of wound healing. Notably, TK-HR activated the MAPK and TGF-ß-Smad signaling pathways by acting on NK1R in RAW264.7 cells and mice. The current work has identified that TK-HR is a potent wound healing regulator that can be applied for the treatment of wounds, including diabetic foot ulcers and infected wounds, in the future.

The effects of Olmesartan/amlodipine administered in the Morning or At Night on nocturnal blood pressure reduction in Chinese patients with mild-moderate essential hypertension (OMAN Trial): study protocol for a prospective, multicenter, randomized, open-label clinical trial {1}.

INTRODUCTION: Hypertension increases the risk of cardiovascular disease. Uncontrolled nocturnal blood pressure is prevalent in patients taking antihypertensive medication, with an incidence rate of 30-60%. Although chronotherapy with antihypertensive agents may provide a new direction for effective control of nocturnal blood pressure, the clinical evidence base remains controversial. This research is presently underway to compare the effects of morning and bedtime administration of antihypertensive medication on nocturnal reduction and circadian rhythm of blood pressure in patients with hypertension. METHODS AND ANALYSIS: This study is being performed as a randomized, multicenter, open-label, parallel-group, clinical trial in which 720 participants are to undergo 24-h ambulatory blood pressure measurement (ABPM) and office blood pressure measurement (OBPM) at baseline before being randomly assigned to a morning (6-10 am) or a bedtime (6-10 pm) administration group. Each participant receives one 20/5-mg tablet of olmesartan/amlodipine (OA) daily for 4 weeks and is then followed up at 4-week intervals for a total of 12 weeks. During follow-up, the OA dosage is adjusted according to the ABPM and OBPM results. Patients with uncontrolled hypertension at the first follow-up visit will receive an increase in OA dosage to 1.5 tablets/day. For patients with blood pressure that is still uncontrolled after a further 4 weeks, the dosage of OA can be increased to 2 tablets/day. The primary objective is the reduction in mean nocturnal systolic blood pressure between baseline and week 12. The secondary objectives are the reduction in ambulatory blood pressure at weeks 4 and 12 and the blood pressure control rate at weeks 4, 8, and 12. DISCUSSION: Antihypertensive chronotherapy remains controversial. A superiority test hypothesis design has been adopted for this trial, in which all participants will be taking the same antihypertensive medication. We anticipate that our findings will determine if nocturnal blood pressure control in Chinese patients with essential hypertension varies according to whether antihypertensive medication is taken in the morning or at bedtime. This study may provide scientific evidence for the application of chronotherapy in clinical practice. TRIAL REGISTRATION: ChiCTR2200059719. Registered on 10 May 2022 ( http://www.chictr.org.cn/edit.aspx?pid=169782&htm=4 ) {2a,2b}.

Novel Amphibian Bowman-Birk-Like Inhibitor with Antioxidant and Anticoagulant Effects Ameliorates Pancreatitis Symptoms in Mice.

Acute pancreatitis (AP) is a serious inflammatory disorder and still lacks effective therapy globally. In this study, a novel Ranacyclin peptide, Ranacin, was identified from the skin of Pelophylax nigromaculatus frog. Ranacin adopted a compact ß-hairpin conformation with a disulfide bond (Cys5-Cys15). Ranacin was also demonstrated effectively to inhibit trypsin and have anticoagulant and antioxidant activities in vitro. Furthermore, the severity of pancreatitis was significantly alleviated in l-Arg-induced AP mice after treatment with Ranacin. In addition, structure-activity studies of Ranacin analogues confirmed that the sequences outside the trypsin inhibitory loop (TIL), especially at the C-terminal side, might be closely associated with the efficacy of its trypsin inhibitory activity. In conclusion, our data suggest that Ranacin can improve pancreatic injury in mice with severe AP through its multi-activity. Therefore, Ranacin is considered a potential drug candidate in AP therapy.

Mortality Risk in Older People Who Drank Alcohol in the Past by Varying Duration of Alcohol Abstention.

INTRODUCTION: This study aims to explore the mortality risk in older people who drank alcohol in the past by varying the duration of alcohol abstention. METHODS: In total, 31,999 participants aged ≥65 years from the Chinese Longitudinal Healthy Longevity Survey (Waves 1998, 2000, 2002, 2005, 2008, 2011, 2014) were included. Duration of alcohol abstention was assessed by designed questions, and the study outcome was all-cause mortality. Cox proportional hazard models were used to examine the association. Analyses occurred from 2022 to 2023. RESULTS: During a follow-up of 140,974.8 person-years, all-cause mortality occurred in 24,257 participants. Mortality significantly increased by 23% (adjusted hazard ratio=1.23, 95% CI=1.14, 1.33, p<0.001), by 17% (adjusted hazard ratio=1.17, 95% CI=1.06, 1.31, p=0.003), and by 17% (adjusted hazard ratio=1.17, 95% CI=1.07, 1.28, p=0.001) in people who drank alcohol in the past with ≤5 years, 5-10 years, 10-20 years of alcohol abstention, respectively, compared with that among those who drink alcohol at present. After 20 years of alcohol abstention, the increased mortality risk disappeared (adjusted hazard ratio=1.06, 95% CI=0.97, 1.15, p=0.204). Stratified and sensitivity analysis revealed similar results. In addition, compared with the risk of all-cause mortality among people who never drink alcohol, the risk of all-cause mortality in those who drank alcohol in the past also significantly increased in the following 20 years after they stop drinking, and then the increased risk disappeared afterward. CONCLUSIONS: An increased risk of all-cause mortality in older people who drank alcohol in the past was observed, which disappeared after 20 years of alcohol abstention.

Formation and Applications in Electronic Devices of Lattice-Aligned Gallium Oxynitride Nanolayer on Gallium Nitride.

Gallium nitride (GaN), a promising alternative semiconductor to Si, is widely used in photoelectronic and electronic technologies. However, the vulnerability of the GaN surface is a critical restriction that hinders the development of GaN-based devices, especially in terms of device stability and reliability. In this study, this challenge is overcome by converting the GaN surface into a gallium oxynitride (GaON) epitaxial nanolayer through an in situ two-step "oxidation-reconfiguration" process. The O plasma treatment overcomes the chemical inertness of the GaN surface, and sequential thermal annealing manipulates the kinetic-thermodynamic reaction pathways to create a metastable GaON nanolayer with a wurtzite lattice. The GaN-derived GaON nanolayer is a tailored structure for surface reinforcement and possesses several advantages, including a wide bandgap, high thermodynamic stability, and large valence band offset with a GaN substrate. These physical properties can be further leveraged to enhance the performance of GaN-based devices in various applications, such as power systems, complementary logic integrated circuits, photoelectrochemical water splitting, and ultraviolet photoelectric conversion.

TLR2-mediated NF-κB signaling pathway is involved in PPV1-induced apoptosis in PK-15 cells.

Porcine parvovirus 1 (PPV1) mainly induces severe reproductive failure in pregnant swine, and causes huge economic losses to the swine industry. Cell apoptosis induced by PPV1 infection has been identified the major cause of reproductive failure. However, the molecular mechanism was not fully elucidated. In this study, the potential mechanism of PPV1 induced apoptosis in PK-15 cells was investigated. Our results showed that PPV1 induced apoptosis in PK-15 cells. Further studies revealed toll-like receptor 2 (TLR2) was involved in the PPV1-mediated apoptosis. TLR2 siRNA significantly decreased the apoptosis. Finally, our study showed NF-κB was activated by TLR2 during PPV1-induced apoptosis. The activation of NF-κB signaling was demonstrated by the phosphorylation of p65, p65 nuclear translocation and degradation of inhibitor of kappa B α (IκBα). Together, these results provided evidence that the recognition between PPV1 and PK-15 cells was mainly through TLR2, and then induction of the NF-κB signaling pathway activation, which further induces apoptosis. Our study could provide information to understand the molecular mechanisms of PPV1 infection.

Intermedin induces autophagy and attenuates hypoxia-induced injury in cardiomyocytes by regulation of MALAT1/ULK1.

Myocardial infarction is a predominant cause of cardiovascular diseases with high incidence and death rate worldwide. Although growing evidence has suggested that IMD has significant protective influences on the cardiovascular system, the molecular regulatory mechanism of IMD in hypoxia-induced injury caused by myocardial infarction is urgent to be elucidated. In the present study, we found hypoxia led to a noteworthy enhancement in IMD expression and IMD alleviated hypoxia-induced myocardial injury of NRCMs. Furthermore, IMD was proved to inhibit hypoxia-induced injury by regulating MALAT1. Our findings suggested MALAT1 positively regulated the mRNA and protein expression level of ULK1 and hypoxia induced autophagy of NRCMs. MALAT1 stimulated autophagy to block hypoxia-induced cell injury in NRCMs via upregulation of ULK1 expression. Autophagy suppression abolished the protective capability of IMD overexpression against hypoxia-induced myocardial injury in NRCMs. In a word, our study shed light on the central mechanism of IMD in preventing hypoxia-induced injury caused by myocardial infarction. We confirmed IMD induced autophagy and attenuated hypoxia-induced injury in cardiomyocytes via MALAT1/ULK1, which may contribute to designing effective therapeutic approaches of myocardial infarction.

Dioscin induces osteosarcoma cell apoptosis by upregulating ROS-mediated P38 MAPK signaling.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Many patients with osteosarcoma readily develop resistance to chemotherapy and have an extremely dismal prognosis. Dioscin, a saponin, is known to exhibit potent anticancer activities and induce cellular death of a variety of cancer types. However, the inhibitory effect of dioscin on osteosarcoma cells and its underlying mechanisms have not been fully elucidated. We investigated the responses of human U2-OS and MG63 osteosarcoma cells to dioscin with regard to proliferation, apoptosis, migration, and invasion, and studied the effect of dioscin on MAPK-related proteins by western blot analysis assays. Dioscin inhibited osteosarcoma cell proliferation, migration, and invasion. Moreover, it induced osteosarcoma cell apoptosis via reactive oxygen species (ROS)-dependent apoptotic signaling. N-acetylcysteine, a reactive oxygen species inhibitor, suppressed dioscin-induced apoptosis, indicating that ROS play an essential role in dioscin-induced apoptosis. Western blot analysis assays showed that p38 MAPK was upregulated after dioscin treatment, and that dioscin induced apoptosis by upregulating ROS-mediated p38 MAPK signaling. Our study suggests that dioscin possesses antitumor activities against human osteosarcoma cells, inhibits osteosarcoma cell proliferation, migration and invasion, and induces osteosarcoma cell apoptosis through upregulating ROS-mediated p38 MAPK signaling. This study may provide a new therapeutic strategy and potential clinical applications for the treatment of osteosarcoma.

Prevalence of Syphilis Infections Among Volunteer Blood Donors in Jinan Blood Center, China: A 15-Year Retrospective Study.

Background: Syphilis infections among volunteer blood donors increased rapidly in recent years. It is important to analyze the demographics of seropositive donor groups and help to recruit donors from low-risk population. Objective: The aim of this study was to analyze the syphilis prevalence among volunteer blood donors in Jinan Blood Center and give direction to blood recruitment. Methods and Materials: A cross-sectional study was conducted among blood donors in Jinan, China. Socio-demographic data and blood donation testing data from January 2007 to December 2021 were extracted from the database of blood management software of Jinan Blood Center for analysis. All blood samples were screened by ELISA, and those anti-TP-positive samples were counted and analyzed by sex, age, educational background, occupation and blood donation times. Logistic regression was used to explore risk factors associated with syphilis infection. Results: Totally 700,757 blood samples were collected in the study during 2007 to 2021, 2290 cases were detected anti-TP positive with a positive rate of 0.33%. Female, 35-44 years old, with a lower education degree, farmers and first-time donors were the high-risk subgroups. Conclusion: Consultation and identification of high-risk population groups should be improved. Measures should be taken to make the donor recruitment more professional and detailed.

Multiple Mechanistic Action of Brevinin-1FL Peptide against Oxidative Stress Effects in an Acute Inflammatory Model of Carrageenan-Induced Damage.

Amphibian skin is acknowledged to contain an antioxidant system composed of various gene-encoded antioxidant peptides, which exert significant effects on host defense. Nevertheless, recognition of such peptides is in its infancy so far. Here, we reported the antioxidant properties and underlying mechanism of a new antioxidant peptide, brevinin-1FL, identified from Fejervarya limnocharis frog skin. The cDNA sequence encoding brevinin-1FL was successfully cloned from the total cDNA of F. limnocharis and showed to contain 222 bp. The deduced mature peptide sequence of brevinin-1FL was FWERCSRWLLN. Functional analysis revealed that brevinin-1FL could concentration-dependently scavenge ABTS+, DPPH, NO, and hydroxyl radicals and alleviate iron oxidation. Besides, brevinin-1FL was found to show neuroprotective activity by reducing contents of MDA and ROS plus mitochondrial membrane potential, increasing endogenous antioxidant enzyme activity, and suppressing H2O2-induced death, apoptosis, and cycle arrest in PC12 cells which were associated with its regulation of AKT/MAPK/NF-κB signal pathways. Moreover, brevinin-1FL relieved paw edema, decreased the levels of TNF-α, IL-1ß, IL-6, MPO, and malondialdehyde (MDA), and restored catalase (CAT) and superoxide dismutase (SOD) activity plus glutathione (GSH) contents in the mouse injected by carrageenan. Together, these findings indicate that brevinin-1FL as an antioxidant has potent therapeutic potential for the diseases induced by oxidative damage. Meanwhile, this study will help us further comprehend the biological functions of amphibian skin and the mechanism by which antioxidants protect cells from oxidative stress.

Immunity analysis against Fowl Adenovirus serotype 4 (FAdV-4) based on Fiber-2 trimer Protein with the different virulence.

Since June 2015, Fowl adenovirus outbreaks have occurred in China, causing significant economic losses to poultry industry. The FAdV-4 Fiber-2 proteins could induce effective protection, but the precise mechanism of immune protection remains unknown. Here, we have compared the biological characteristics of Fiber-2 protein of the very virulent WZ strain of FAdV-4 (vvFAdV-4) with that of non-virulent ON1 strain. The sequence analysis revealed natural deletions and sequence differences between the classical non-pathogenic strain ON1 and the vvFAdV-4 isolate. These two Fiber-2 proteins successfully expressed in E. coli resemble in structure and function to the native-like trimeric protein. The trimeric structure and bioreactivity of the recombinant Fiber-2 proteins to FAdV-4 specific antibodies were characterized. The immune protection induced by Fiber-2 proteins of FAdV-4 WZ and ON1 strains were compared in SPF chickens. All birds in the WZ-Fiber-2 immunized group generated systemic specific antibodies compared with both ON1-Fiber-2 protein and PBS immunized groups. According to the results of attack mortalities, viral shedding and tissue gross lesion, the WZ Fiber-2 protein induced complete protection at a dose of 2 µg per chicken, whereas the ON1-Fiber-2 protein induced 0 protection at 3 dpc. In view of the characteristics of Fiber-2 proteins of different strains, this study can help us to further understand the mechanism of protective immunity and provide a basis for the prevention and control of FAdV-4 in chickens.

Evaluation of parallel endplate osteotomy for severe rigid spinal deformities: a retrospective analysis of 36 cases with a minimum 2-year follow-up.

BACKGROUND: To report on the technique and results of parallel endplate osteotomy (PEO) for severe rigid spinal deformity. METHODS: We retrospectively reviewed the clinical data of 36 patients with severe rigid spinal deformities who underwent PEO between July 2016 and December 2018 and who were followed up for at least 24 months. RESULTS: Following PEO, the kyphosis and scoliosis correction rates reached 77.4 ± 14.0% and 72.2 ± 18.2%, respectively. The median intraoperative estimated blood loss was 1500 mL and the median operative time was 6.8 h. The SF-36 scores of physical function, role-physical, bodily pain, general health, vitality, social function, role-emotional and mental health changed from 62 ± 28, 51 ± 26, 49 ± 29, 35 ± 30, 53 ± 28, 45 ± 30, 32 ± 34 and 54 ± 18 at baseline to 81 ± 16, 66 ± 41, 72 ± 40, 64 ± 44, 75 ± 25, 71 ± 46, 66 ± 34 and 76 ± 28 at 12 months postoperatively, 82 ± 32, 67 ± 42, 81 ± 30, 71 ± 41, 80 ± 30, 74 ± 36, 68 ± 35 and 85 ± 33 at 18 months postoperatively, and 86 ± 21, 83 ± 33, 88 ± 26, 79 ± 39, 86 ± 36, 86 ± 48, 80 ± 47 and 91 ± 39 at 24 months postoperatively, respectively. CONCLUSIONS: PEO is an effective technique for successful correction of spinal deformities. At the two-year follow-up visit, all patients achieved better clinical results based on the SF-36 scores.

Associations of urinary sodium excretion with central hemodynamics and changes in vascular structure and function at high altitude.

Research reports on associations of urinary sodium excretion with central hemodynamic parameters and vascular changes are quite limited in general or non-hypertensive population. The purpose of the current study was to explore such associations in Chinese general Tibetans living at high altitude. This cross-sectional study was conducted in Luhuo County, Ganzi Tibetan Autonomous Prefecture with average elevation of 3800 meters from December 2018 to January 2019. A total of 294 Tibetans were included in the current study. Twenty-four hour urinary sodium excretion was estimated by second fasting spot urine in the morning using Kawasaki formula. Central hemodynamic parameters, including central systolic blood pressure (CSBP), central diastolic blood pressure (CDBP), central pulse pressure (CPP), central mean arterial pressure (CMAP), augmentation pressure (AP), and augmentation index standardized for heart rate of 75 (AIx75 ), were evaluated using the SphygmoCor system. Vascular structures and functions were assessed by carotid intima media thickness (CIMT) test and brachial ankle pulse wave velocity (baPWV), respectively. Estimated mean 24h urinary sodium excretion of Tibetans in Luhuo County was 5.26±1.61 g. After adjustment, estimated 24h urinary sodium was positively associated with CSBP (ß = 1.15, p = .008) and CPP (ß = 0.87, p = .013). Line graph of means across urinary sodium quartiles showed that associations of 24 h urinary sodium excretion with AIx75 and baPWV presented approximate "J" shape after controlling for confounders. Estimated 24 h sodium excretion was independently and positively associated with CSBP and CPP. Moreover, association between urinary sodium excretion and arterial elasticity, as evaluated by baPWV and AIx75 , presented "J" shape. Further studies are needed to verify J-shaped association and "safe" zone of sodium intake.

Combined evaluation of coronary artery disease and high-sensitivity cardiac troponin T for prediction of adverse events in patients with hypertrophic cardiomyopathy.

BACKGROUND: This study was performed to investigate the clinical significance of combined evaluation of both coronary artery disease (CAD) and high-sensitivity cardiac troponin T (hs-cTnT) for prediction of major adverse cardiovascular events (MACEs) in patients with hypertrophic cardiomyopathy (HCM). METHODS: We performed clinical evaluations, including coronary artery imaging and hs-cTnT measurement, in 162 patients with HCM. RESULTS: The patients were followed up for a median period of 3.7 years (interquartile range 2.4-5.6 years; total of 632.3 person-years [PYs]), during which time MACEs occurred in 24 (14.8%) patients. The incidence of MACEs was 6.4 and 2.7 per 100 PYs for patients with CAD and normal coronary arteries, respectively; similarly, the incidence was 5.8 and 2.1 per 100 PYs in patients with an elevated hs-cTnT concentration (> 14.0 ng/L) and a normal hs-cTnT concentration, respectively. The multivariate analysis suggested that CAD and an elevated hs-cTnT concentration tended to be positively associated with MACEs. When the groups were allocated according to these two markers, the patients were divided into four groups, which further improved the predictive values. The incidence of MACEs was 10.4 per 100 PYs in the CAD and elevated hs-cTnT group, which was much higher than the incidence in all other groups (range, 2.0-3.5 per 100 PYs). With the normal coronary arteries and normal hs-cTnT group serving as a reference, the adjusted hazard ratio was 5.0 (95% confidence interval 1.0-23.8; P = 0.046) for the CAD and elevated hs-cTnT group. In addition, the subgroup analysis showed similar findings among the patients without severe CAD. CONCLUSIONS: In patients with HCM, combined evaluation of both CAD and hs-cTnT might facilitate more reliable prediction of MACEs than evaluation of a single marker. These may serve as clinically useful markers to guide risk management.

Assessment and validation of three spot urine assay methods for the estimation of 24-hour urinary sodium excretion in Chinese Tibetan adults living in the mountains.

Twenty-four-hour urine collection is the gold standard method for the evaluation of salt intake, but it is often impractical in large-scale investigations, especially in resource-poor areas. Methods for the estimation of 24-hour urinary sodium excretion (USE) using a spot urine sample have been established, but have not been validated in Chinese Tibetans. Therefore, the authors aimed to evaluate the Kawasaki, Tanaka, and the International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) formulas for the prediction of 24-hour USE in Chinese Tibetan adults. The authors analyzed the bias, correlation, agreements between estimated values and measured values, and the relative and absolute differences and misclassification at the individual level for the three methods in 323 Tibetan participants from the Ganzi Tibetan Autonomous Prefecture of Sichuan Province, China. The mean biases between the measured values and the estimated 24-hour USE using the Kawasaki, Tanaka, and INTERSALT methods were 5.4 mmol/day (95% confidence interval [CI]: 0.8-10.1 mmol/day), -40.8 mmol/day (95% CI: -44.6 to -36.9 mmol/day), and -57.1 mmol/day (95% CI: -61.9 to -52.4 mmol/day), respectively. The Pearson correlation coefficients for the relationships between the measured values and the estimated 24-hour USE were 0.43 (Kawasaki), 0.38 (Tanaka), and 0.27 (INTERSALT), respectively (all p < .01). The intraclass correlation coefficients showed similar patterns to the correlation data: 0.47 for Kawasaki, 0.40 for Tanaka, and 0.27 for INTERSALT (all p < .01). The upper and lower limits of agreement between the measured values and the estimated 24-hour USE were -92.6 and 81.8 mmol/day for the Kawasaki method, -28.5 and 110.0 mmol/day for the Tanaka method, and -28.4 and 142.7 mmol/day for the INTERSALT method. Compared with the other two methods, the percentage of individuals that were misclassified by using the Kawasaki method was 48.2%, while those for the Tanaka and INTERSAL methods was 72.1% and 75.5%, respectively. However, when an individual's salt intake was higher than 12.8 g/day, the misclassification rates of the Kawasaki, Tanaka, and INTERSALT methods were 20%, 90%, and 97.5%, respectively. Thus, the authors found that the Kawasaki equation may have performed better than the other equations at Chinese Tibetan population level assessment, but none of these equations are suitable for use or perform well at the individual level. A more accurate method of using a spot urine sample to evaluate individual 24-hour USE for Tibetans is needed.

Inhibition of PI3K/Akt/mTOR pathway by ammonium chloride induced apoptosis and autophagy in MAC-T cell.

Ammonia is a harmful gas with a pungent odor, participates in the regulation of a variety of apoptosis and autophagy, which in turn affects the growth and differentiation of cells. To test the regulation of NH3 on the apoptosis and autophagy of mammary epithelial cells, we selected NH4Cl as NH3 donor in vitro model. MTT and CCK-8 assay kits were employed to detect cell activity. Real-time quantitative PCR and western blot methods were used to detect the abundance of inflammatory molecules, apoptosis markers, and autophagy genes. We selected TUNEL kit and the Annexin-FITC/PI method to detect apoptosis. TEM analysis was used to detect autophagic vesicles, and MDC stain evaluated the formation of autophagosome. The results indicated that NH4Cl reduced cell viability in a concentration-dependent manner and promoted cell inflammatory response, apoptosis, and autophagy. NH4Cl stimulation notable increased the autophagosomes number. Interestingly, we also detected that the addition of LY294002 and Rapamycin inhibited the PI3K/Akt pathway and the mTOR pathway, respectively, resulting in changes in both apoptosis and autophagy. Therefore, we draw a conclusion that NH3 may regulate the apoptosis and autophagic response of bovine mammary epithelial cells through the PI3K/Akt/mTOR signaling pathway. Further investigations on ammonia's function in other physiological respects, will be critical to provide theoretical help for the improvement of production performance. It will be also helpful for controlling the harmful gas ammonia concentration in the livestock house to protect the health of dairy cows.