Vitamin A Promotes the Repair of Mice Skeletal Muscle Injury through RARα.

Vitamin A (VitA) is an important fat-soluble vitamin which plays an important role in cell growth and individual development. However, the effect of VitA on the repair process of muscle injury and its molecular mechanism are still unclear. In this study, VitA and RA were first added to the culture medium of differentiated cells. We then detected cell differentiation marker proteins and myotube fusion. Moreover, the effects of VitA on RARα expression and nuclear translocation were further examined. The results showed that VitA significantly promoted the differentiation of C2C12, and the expression of RARα was significantly increased. Furthermore, VitA was injected into skeletal muscle injury in mice. HE staining and Western Blot results showed that VitA could significantly accelerate the repair of skeletal muscle injury and VitA increase the expression of RARα in mice. This study provides a theoretical basis for elucidating the regulation mechanism of VitA-mediated muscle development and the development of therapeutic drugs for muscle diseases in animals.

Identification of indications for albumin administration in septic patients with liver cirrhosis.

BACKGROUND: Albumin infusion is the primary therapeutic strategy for septic patients with liver cirrhosis. Although recent studies have investigated the efficacy of albumin in the resuscitation stage of septic patients with liver cirrhosis, it remains unclear whether daily albumin administration can improve outcomes. Furthermore, the indications for initiating albumin therapy are not well defined. METHODS: Septic patients with liver cirrhosis were obtained from the Medical Information Mart for Intensive Care (MIMIC-IV 2.0) database. Marginal structural Cox models were employed to investigate the association between daily albumin infusion and 28-day mortality. We also aimed to explore under what circumstances enrolled patients could benefit most from albumin administration, based on the clinical parameters collected on the day of albumin infusion, including serum albumin concentration, serum lactate concentration, mean arterial pressure (MAP), and vasopressor dosage. RESULTS: A total of 2265 patients were included in the final analysis, of whom 1093 (48.3%) had received albumin treatment at least once. The overall 28-day mortality was 29.6%. After marginal structural modeling, daily albumin infusion was associated with a reduced risk of 28-day death (hazard ratio, 0.76; 95% CI 0.61-0.94). We found that patients benefit most from albumin infusion when initiated on the day of serum albumin concentration between 2.5 and 3.0 g/dL, serum lactate concentration greater than or equal to 2 mmol/L, MAP less than 60 mmHg, or vasopressor dosage between 0.2 and 0.3 mcg/kg/min (norepinephrine equivalent, NEE). CONCLUSIONS: Albumin infusion is associated with a reduction in mortality in septic patients with liver cirrhosis under specific circumstances. Serum albumin concentration, serum lactate, MAP, and vasopressor dosage were found to be modifiers of treatment effectiveness and should be considered when deciding to initial albumin infusion.

The Effect of an Essential Oil Blend on Growth Performance, Intestinal Health, and Microbiota in Early-Weaned Piglets.

Essential oils (EO) are promising feed additives for their antibacterial, antioxidant, and immune-enhancing abilities with low toxicity. Carvacrol, thymol, and cinnamaldehyde are commonly used to synthesize EO. However, few studies focus on combining these three EO in early-weaned piglets. In the present study, 24 piglets weaned at 21 d of age were randomly divided into 2 groups (6 replicate pens per group, 2 piglets per pen). The piglets were fed a basal diet (the control group) and a basal diet supplemented with 400 mg/kg EO (a blend consisting of carvacrol, thymol, and cinnamaldehyde, the EO group) for 28 days. At the end of the experiment, one piglet per pen was randomly chosen to be sacrificed. Growth performance, hematology, plasma biochemical indices, antioxidant capacity, intestinal epithelial development and immunity, colonic volatile fatty acids (VFA), and microbiota were determined. The results indicated that the diet supplemented with EO significantly improved average daily feed intake (ADFI, p < 0.01) and average daily gain (ADG, p < 0.05) in the day 0 to 28 period. EO supplementation led to a significant decrease in plasma lysozyme (p < 0.05) and cortisol levels (p < 0.01). Additionally, EO significantly promoted jejunal goblet cells in the villus, jejunal mucosa ZO-1 mRNA expression, ileal villus height, and ileal villus height/crypt depth ratio in piglets (p < 0.05). The ileal mucosal TLR4 and NFκB p-p65/p65 protein expression were significantly inhibited in the EO group (p < 0.05). Colonic digesta microbiota analysis revealed that bacteria involving the Erysipelotrichaceae family, Holdemanella genus, Phascolarctobacterium genus, and Vibrio genus were enriched in the EO group. In conclusion, these findings indicate that the EO blend improves ADG and ADFI in the day 0 to 28 period, as well as intestinal epithelial development and intestinal immunity in early-weaned piglets, which provides a theoretical basis for the combined use of EO in weaned piglets.

Identifying high-risk phenotypes and associated harms of delayed time-to-antibiotics in patients with ICU onset sepsis: A retrospective cohort study.

PURPOSE: To identify phenotypes of Intensive Care Unit (ICU) onset sepsis and its associated harms of delayed time-to-antibiotics. MATERIALS AND METHODS: The Medical Information Mart for Intensive Care IV (MIMIC-IV) database was employed to identify patients with ICU onset sepsis. The primary exposure was time-to-antibiotics, as measured from sepsis recognition to first antibiotic administered. Latent profile analysis (LPA) was used to identify phenotypes of sepsis based on individual organ failure score derived from Sequential Organ Failure Assessment (SOFA). Interactions between phenotypes and time-to-antibiotics on 28-day mortality were explored. RESULTS: 6246 patients were enrolled in final analysis. The overall 28-day mortality was 12.7%. Delayed time-to-antibiotics was associated with increased 28-day mortality in patients with ICU onset sepsis (HR 1.12, 95% CI 1.08-1.18). Four phenotypes of sepsis were identified: phenotype 1 was characterized by respiratory dysfunction, phenotype 2 was characterized by cardiovascular dysfunction, phenotype 3 was characterized by multiple organ dysfunction, and phenotype 4 was characterized by neurological dysfunction. The adjusted HR of 28-day mortality was 1.16 (95% CI 1.08-1.25) in phenotype 1, and 1.06 (95% CI 1.00-1.13) in phenotype 2, while no significant interaction was observed. CONCLUSIONS: Septic patients with respiratory or cardiovascular dysfunction were associated with harms of delayed time-to-antibiotics.

Effects of dietary ß-1,3-glucan addition on the growth performance, mRNA expression in jejunal barrier, and cecal microflora of broilers challenged with Clostridium perfringens.

This experiment aimed to explore the interaction of ß-1,3-glucan and Clostridium perfringens on the growth performance, intestinal health and cecal microflora of broilers. A total of 384 one-day-old Arbor Acre broilers were sorted into 4 treatments with 6 replications. There were 2 factors in this trial: dietary ß-1,3-glucan addition including 0 and 250 mg/kg, intestinal enteritis challenged with Clostridium perfringens attack or not. Results showed that Clostridium perfringens infection disrupted the integrity of the intestinal mucosa by reducing the jejunal Occludin and Claudin-1 mRNA expression of broiler chickens at 21 d of age (P < 0.05). Meanwhile, when considering Clostridium perfringens as the main effect, it also decreased the mRNA expression of the glucose transporter recombinant sodium/glucose cotransporter 1 (SGLT1) at d 21 and the fatty acid transporter liver fatty acid-binding protein (L-FABP) at d 42 (P < 0.05) as well as affect cecum microbial diversity, especially in relative abundance of Firmicutes and Bacteroidetes. In addition, Clostridium perfringens infection reduced body weight, daily weight gain, and feed-gain ratio (FCR) in broilers at d 42 (P < 0.05). The dietary ß-1,3-glucan could alleviate intestinal mucosal damage caused by the Clostridium perfringens to some extent. When considering ß-1,3-glucan as the main effect, it increased the SGLT1 at 42 d of age (P < 0.05), and stabilized gut microbiota disorder caused by Clostridium perfringens. More over dietary ß-1,3-glucan addition increased body weight at 42-day-old (P < 0.05), and improved daily weight gain and FCR during 1 to 42 d (P < 0.05). In conclusion, dietary ß-1,3-glucan could improve growth performance and intestinal health in broilers infected with Clostridium perfringens.

Butenolides from the Coral-Derived Fungus Aspergillius terreus SCSIO41404.

Five undescribed butenolides including two pairs of enantiomers, (+)-asperteretal G (1a), (-)-asperteretal G (1b), (+)-asperteretal H (2a), (-)-asperteretal H (2b), asperteretal I (3), and para-hydroxybenzaldehyde derivative, (S)-3-(2,3-dihydroxy-3-methylbutyl)-4-hydroxybenzaldehyde (14), were isolated together with ten previously reported butenolides 4-13, from the coral-derived fungus Aspergillus terreus SCSIO41404. Enantiomers 1a/1b and 2a/2b were successfully purified by high performance liquid chromatography (HPLC) using a chiral column, and the enantiomers 1a and 1b were new natural products. Structures of the unreported compounds, including the absolute configurations, were elucidated by NMR and MS data, optical rotation, experimental and calculated electronic circular dichroism, induced circular dichroism, and X-ray crystal data. The isolated butenolides were evaluated for antibacterial, cytotoxic, and enzyme inhibitory activities. Compounds 7 and 12 displayed weak antibacterial activity, against Enterococcus faecalis (IC50 = 25 µg/mL) and Klebsiella pneumoniae (IC50 = 50 µg/mL), respectively, whereas 6 showed weak inhibitory effect on acetylcholinesterase. Nevertheless, most of the butenolides showed inhibition against pancreatic lipase (PL) with an inhibition rate of 21.2-73.0% at a concentration of 50 µg/mL.

The NCOA1-CBP-NF-κB transcriptional complex induces inflammation response and triggers endotoxin-induced myocardial dysfunction.

Inflammatory pathways represented by TLR4/NF-κB (Toll-like receptor 4/Nuclear factor-κB) axis signaling are activated in the pathogenesis of endotoxin-induced myocardial dysfunction (EIMD). However, the underlying mechanism by which NF-κB coordinates with other transcriptional coactivators/corepressors to regulate the expression of proinflammatory cytokine genes remains unclear. We established an EIMD-mouse model by intraperitoneal injection of lipopolysaccharides (LPS), and we discovered that NCOA1 (nuclear receptor coactivator 1) assembled with CBP (CREB binding protein) and NF-κB subunits to form a transcriptional complex that specifically bound to promoters of proinflammatory cytokine genes to activate their expression. LPS treatment also inhibited DNMT1 (DNA methyltransferase 1) expression, thereby decreasing DNA methylation of a CpG island located on the promoter of NCOA1 and causing NCOA1 overexpression. Screening small molecules that abolished NCOA1-CBP interaction in a yeast system identified a compound PSSM2126 that effectively blocked the NCOA1-CBP interaction in vitro and in vivo. Administration of PSSM2126 to EIMD mice significantly alleviated the inflammation response and improved cardiac function. Collectively, our results reveal that an NCOA1-dependent transactivation mechanism can regulate proinflammatory cytokine expression, thereby improving our understanding of the activation of NF-κB targets. The promising inhibition of the NCOA1-CBP interaction by PSSM2126 may provide a new therapeutic option for EIMD.

The Roles of Life Satisfaction and Community Recreational Facilities in the Relationship between Loneliness and Depression in Older Adults.

OBJECTIVES: This study examined the mediating effect of life satisfaction and the moderating effect of the availability of community recreational facilities (CRF) in the association between loneliness and depression in rural older adults and urban older adults, respectively. METHODS: Quantitative data collected from 7547 Chinese older adults were analyzed using the SPSS macro PROCESS to test a moderated mediation model with life satisfaction as the mediator and CRF availability and residency type (rural vs. urban) as moderators. RESULTS: Loneliness negatively predicted life satisfaction, life satisfaction negatively predicted depression, and loneliness positively predicted depression. The interaction of loneliness and CRF availability had a significant effect on depression for urban older adults but not for rural older adults. The direct impact of loneliness on depression differed significantly between rural and urban older adults. CONCLUSIONS: Life satisfaction mediated the association between loneliness and depression in both rural and urban older adults; CRF availability unexpectedly boosted the effect of loneliness on depression in urban older adults but not in rural older adults. Given the same level of loneliness, urban older adults were more likely to be depressed than rural older adults. CLINICAL IMPLICATIONS: Psychogeriatric practitioners may embed life satisfaction into intervention programs to minimize depression among older adults. Public administrators should examine the utilization of public facilities to avoid wasted resources and counterproductive effects on older adults. Lonely urban older adults deserve special attention.

Targeting the TXNIP-NLRP3 interaction with PSSM1443 to suppress inflammation in sepsis-induced myocardial dysfunction.

Sepsis-induced myocardial dysfunction (SIMD), a deadly symptom in sepsis patients, is mainly caused by cardiovascular inflammation. However, it remains unclear how systemic inflammation triggers and aggravates cardiovascular inflammation in the pathogenesis of SIMD. This study found that proinflammatory cytokines and H2 O2 concentrations were significantly induced in SIMD-mice. In particular, a microarray analysis of CD63+ exosomes isolated from sham- and SIMD-monocytes revealed a significant induction of thioredoxin-interacting protein (TXNIP) and NLR family pyrin domain-containing 3 (NLRP3). We proved that oxidative stress caused the disassociation of the TXNIP-TRX2 (thioredoxin 2) complex and the assembly of the TXNIP-NLRP3 complex. In addition, this finding showed that the latter complex could be embedded into CD63+ exosomes and traffic from monocytes to the resident heart macrophages, where it activated caspase-1 and cleaved inactive interleukin 1ß (IL-1ß) and IL-18. Furthermore, using an amplified luminescent proximity homogeneous assay (Alpha) with GST-TXNIP and His-NLRP3, we obtained a small molecule named PSSM1443 that could disrupt the TXNIP-NLRP3 interaction in vitro, impairing NLRP3 downstream events. Of note, after administering PSSM1443 to the SIMD-mice, we found the small molecule could significantly suppress the activation of caspase-1 and the cleavage of pro-IL-1ß and pro-IL-18, reducing inflammation in the SIMD-mice. Collectively, our results reveal that monocyte-derived exosomes harbor the overexpressed TXNIP-NLRP3 complex, which traffics from circulating monocytes to local macrophages and promotes the cleavage of inactive IL-1ß and IL-18 in the macrophages, aggravating cardiovascular inflammation. PSSM1443 functions as an inhibitor of the TXNIP-NLRP3 complex and its administration can decrease inflammation in SIMD-mice.

How Does Perceived Health Status Affect Depression in Older Adults? Roles of Attitude toward Aging and Social Support.

Objectives: This study aims to test the mediating effect of attitude toward aging and the moderating effect of social support in the association between perceived health status and depression in older adults. Methods: The study hypotheses were tested by using quantitative data collected from 6485 Chinese older adults. SPSS macro PROCESS was employed to analyze the data. Results: The results show that the relationship between perceived health status and depression in older adults is mediated by their attitude toward aging. In addition, both direct and indirect impacts of perceived health status on depression are significantly buffered by social support. Conclusions: This study suggests a potential mediating role of attitude toward aging and a moderating role of social support in the association between physical health and mental health among older adults. Clinical Implications: The findings of the study suggest that clinicians might need to consider attitudes toward aging along with social support as they work with older adults with comorbid physical illnesses and depression. The findings also reveal that social support is not only about the external resources that older adults need to cope with stressful life events, but also serves as an inner sustenance to make older adults less sensitive to the deleterious effects of poor health status and negative attitude toward aging.

What Can Buffer the Impact of Social Support on Chinese Older Adults' Life Satisfaction?

This study aims to test the moderating effects of home health care, home-help service, and older adults' attitudes toward aging on the relationship between social support and life satisfaction among Chinese older adults. The study used a sample of 5,578 Chinese home-dwelling older adults. Multiple linear regression analyses were performed to test the hypothesized effects along with gender and Hukou type differences. The results show that home health care significantly buffers the impact of social support on life satisfaction, and this buffering effect remains same across gender groups and Hukou groups. The findings of the study provide unique and contemporary theoretical and practical implications.

The small molecule PSSM0332 disassociates the CRL4ADCAF8 E3 ligase complex to decrease the ubiquitination of NcoR1 and inhibit the inflammatory response in a mouse sepsis-induced myocardial dysfunction model.

Sepsis-induced myocardial dysfunction (SIMD) is a life-threatening complication caused by inflammation, but how it is initiated is still unclear. Several studies have shown that extracellular high mobility group box 1 (HMGB1), an important cytokine triggering inflammation, is overexpressed during the pathogenesis of SIMD, but the underlying mechanism regarding its overexpression is still unknown. Herein, we discovered that CUL4A (cullin 4A) assembled an E3 ligase complex with RBX1 (ring-box 1), DDB1 (DNA damage-binding protein 1), and DCAF8 (DDB1 and CUL4 associated factor 8), termed CRL4ADCAF8, which ubiquitinated and degraded NcoR1 (nuclear receptor corepressor 1) in an LPS-induced SIMD mouse model. The degradation of NcoR1 failed to form a complex with the SP1 transcription factor, leading to the upregulation of HMGB1. Mature HMGB1 functioned as an effector to induce the expression of proinflammatory cytokines, causing inflammation and resulting in SIMD pathology. Using an in vitro AlphaScreen technology, we identified three small molecules that could inhibit the CUL4A-RBX1 interaction. Of them, PSSM0332 showed the strongest ability to inhibit the ubiquitination of NcoR1, and its administration in SIMD mice exhibited promising effects on decreasing the inflammatory response. Collectively, our results reveal that the CRL4ADCAF8 E3 ligase is critical for the initiation of SIMD by regulating the expression of HMGB1 and proinflammatory cytokines. Our results suggest that PSSM0332 is a promising candidate to inhibit the inflammatory response in the pathogenesis of SIMD, which will provide a new option for the therapy of SIMD.

Freezing More than Gait: A Case Report of Freezing of Urination (FOU) in Parkinson's Disease.

Freezing of gait (FOG) is a disabling phenomenon that is described by patients with Parkinson's disease (PD). Not only gait may be involved in the freezing phenomenon, but also some nonmotor symptoms, such as freezing of urination (FOU) in this case. The characters of urinary dysfunctions in this case resemble "off" freezing: (1) abrupt difficulty in starting or continuing in urination; (2) the urinary dysfunctions fluctuated with medication state; and (3) the urinary dysfunctions could be alleviated dramatically by an external cueing. Urinary dysfunctions in this patient (and maybe more PD patients) are associated not only with the classical "nonmotor symptoms" but also the freezing phenomenon. FOU could be a part of the spectrum of freezing symptoms. The subtypes of the freezing phenomenon will shed light on the PD pathophysiology and clinical treatment.

New pestallic acids and diphenylketone derivatives from the marine alga-derived endophytic fungus Pestalotiopsis neglecta SCSIO41403.

Three new carboxylic acid derivatives, pestallic acids F and G (1 and 2), pestalotiopyrone N (3), and a new diphenylketone derivative named neopestalone (5) were obtained from the liquid cultures of marine alga-derived endophytic fungus Pestalotiopsis neglecta SCSIO41403, along with six known compounds (4, 6-10). The structures of those new compounds were elucidated mainly by analysis of their NMR and MS data. The isolated compounds were evaluated for their anti-Dengue virus and COX-2 inhibitory activities, and two diphenylketone derivatives (5 and 6) exhibited obvious COX-2 inhibitory activities, with the IC50 values being 5.8 and 3.4 µM, respectively.

Perceived Health and Life Satisfaction of Elderly People: Testing the Moderating Effects of Social Support, Attitudes Toward Aging, and Senior Privilege.

As health declines with age, it is critical to explore moderators that could buffer the impact of declining health on life satisfaction of elderly people. This study aims to test the moderating effects of social support, attitudes toward aging, and senior privilege on the relationship between perceived health and life satisfaction among elderly people. The study used a sample of 5809 Chinese elderly people. Multiple regression analyses were performed to test the moderating effects of the study variables along with gender difference. The results show that social support and attitudes toward aging do not moderate the relationship between perceived health and life satisfaction; senior privilege however, amplifies the impact of perceived health on life satisfaction for female elderly people. The findings recommend personalized provision of senior privilege based on health status and types of diseases, rather than only based on age; and suggest tailored female-oriented social services such as psychological counseling and humanistic care.

Pyrola incarnata demonstrates neuroprotective effects against ß-amyloid-induced memory impairment in mice.

This study aims to investigate the neuroprotective effects of Pyrola incarnata against ß-amyloid-induced memory impairment in mice. Ethanol extract of Pyrola incarnata (EPI) was obtained and led to eleven phytochemicals successfully by isolation and purification, which were elucidated by spectroscopic analysis (1H NMR, 13C NMR and HR-ESI-MS). Thereinto, ursolic acid was gained as most abundant monomer. C57BL/6 mice were intracerebroventricular injected with aggregated Aß25-35. Open-field test, Barnes maze test and Morris water maze were conducted for evaluating cognition processes of EPI and ursolic acid. EPI significantly improved learning and memory deficits, attenuated the Aß25-35 level of deposition immunohistochemically. Further studies revealed that ursolic acid as bioactive phytochemical of P. incarnata improved spatial memory performance and ameliorated Aß25-35 accumulation by activating microglia cells and up-regulating Iba1 level in the hippocampus. These findings suggest P. incarnata could improve the cognition of mice and be a promising natural source for the treatment of neurodegenerative disease.

Prognostic factors for generalized tetanus in adults: A retrospective study in a Chinese hospital.

BACKGROUND: We evaluated factors associated with mortality in patients with moderate/severe generalized tetanus. METHODS: This retrospective study included patients with moderate/severe generalized tetanus admitted to the Affiliated Hospital of Nantong University (China) between January 2005 and January 2017. Clinical data were extracted from medical records. Patients were divided into two groups based on outcome (survival or death). Factors associated with mortality were analyzed using univariate and multivariate logistic regression. RESULTS: Seventy-five patients were included (57.3% male; age, 57.9 ±â€¯18.4 years; APACHE II score, 10.6 ±â€¯3.4; severe tetanus, 49.3%; mortality, 25.3%). Multivariate analysis identified severe tetanus (odds ratio [OR], 30.364; 95% confidence interval [CI], 2.459-374.896) and APACHE II score (OR, 1.536; 95%CI, 1.051-2.243) as positively associated with mortality, whereas high-calorie nutrition (OR, 0.027; 95%CI, 0.002-0.359) and dexmedetomidine use (OR, 0.035; 95%CI, 0.003-0.467) were negatively associated with mortality (all P < 0.05). CONCLUSION: Tetanus severity and APACHE II score were associated with mortality in patients with generalized tetanus, whereas high-calorie nutrition and dexmedetomidine use reduced the odds of death. High-calorie nutrition and dexmedetomidine administration may improve prognosis in adult patients with moderate/severe generalized tetanus.

Antioxidant activity against H2O2-induced cytotoxicity of the ethanol extract and compounds from Pyrola decorate leaves.

CONTEXT: The leaves of Pyrola decorate H. Andr (Pyrolaceae), known as Luxiancao, have long been used for treating kidney deficiency, gastric haemorrhage and rheumatic arthritic diseases in traditional Chinese medicine. OBJECTIVE: The phytochemicals and antioxidant capacities in vitro of P. decorate leaves were investigated. MATERIALS AND METHODS: Ethanol, petroleum ether, acetidin, n-butyl alcohol and aqueous extracts of Pyrola decorate leaves were prepared by solvent sequential process, and then isolated and purified to obtain phytochemicals. Cell viability was measured by MTT assay. PC12 cells were pretreated for 24 h with different extractions of P. decorate leaves at concentrations of 0.1, 0.5, 1, 5 and 10 mg/mL, then H2O2 of 0.4 mM was added in all samples for an additional 2 h. The antioxidant capacities of betulin, ursolic acid and monotropein were determined in PC12 cells against H2O2 induced cytotoxicity in vitro as well. RESULTS: Nine compounds (1-9) were isolated and structurally determined by spectroscopic methods, especially 2D NMR analyses. Ethanol extract treated groups showed inhibitory activity with IC50 value of 10.83 mg/mL. Betulin, ursolic acid and monotropein were isolated from P. decorate, and demonstrated with IC50 values of 6.88, 6.15 and 6.13 µg/mL, respectively. DISCUSSION AND CONCLUSIONS: In conclusion, Pyrola decorate is a potential antioxidative natural plant and worth testing for further pharmacological investigation in the treatment of oxidative stress related neurological disease.

The evolving concept of physiological ischemia training vs. ischemia preconditioning.

Ischemic heart diseases are the leading cause of death with increasing numbers of patients worldwide. Despite advances in revascularization techniques, angiogenic therapies remain highly attractive. Physiological ischemia training, which is first proposed in our laboratory, refers to reversible ischemia training of normal skeletal muscles by using a tourniquet or isometric contraction to cause physiologic ischemia for about 4 weeks for the sake of triggering molecular and cellular mechanisms to promote angiogenesis and formation of collateral vessels and protect remote ischemia areas. Physiological ischemia training therapy augments angiogenesis in the ischemic myocardium by inducing differential expression of proteins involved in energy metabolism, cell migration, protein folding, and generation. It upregulates the expressions of vascular endothelial growth factor, and induces angiogenesis, protects the myocardium when infarction occurs by increasing circulating endothelial progenitor cells and enhancing their migration, which is in accordance with physical training in heart disease rehabilitation. These findings may lead to a new approach of therapeutic angiogenesis for patients with ischemic heart diseases. On the basis of the promising results in animal studies, studies were also conducted in patients with coronary artery disease without any adverse effect in vivo, indicating that physiological ischemia training therapy is a safe, effective and non-invasive angiogenic approach for cardiovascular rehabilitation. Preconditioning is considered to be the most protective intervention against myocardial ischemia-reperfusion injury to date. Physiological ischemia training is different from preconditioning. This review summarizes the preclinical and clinical data of physiological ischemia training and its difference from preconditioning.

Development of Ophiocordyceps sinensis through Plant-Mediated Interkingdom Host Colonization.

Ophiocordyceps sinensis is a well-known entomogenous and medicinal fungus. After its anamorphs parasitize the larvae of the genus Thitarodes, fruit-bodies may form to be used as medicine. However, its developmental mechanisms remain unknown. The distribution of O. sinensis was determined in different tissues of the Thitarodes larvae and the dominant plant species using real-time quantitative polymerase chain reaction (qPCR) and fluorescence in situ hybridization (FISH) technique, respectively. We found that more fungal material was located in plants than in larvae, especially in Ranunculus tanguticus. A considerable amount was detected in larval intestinal-wall and plant roots. It is suggested that plants are the potential hosts of O. sinensis, which modifies our understanding of the life cycle of O. sinensis and indicates that the phytophagous larvae may become infected as they feed. Our research may contribute to the study of systematic evolution and population ecology of O. sinensis, elucidate its developmental mechanism and promote sustainable harvesting.