Biomarkers, signaling pathways, and programmed cell death in acute lung injury and its treatment with Traditional Chinese Medicine: a narrative review.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common life-threatening, high-mortality lung diseases associated with acute and severe inflammation of the lungs. However, research on diagnostic markers and signaling pathways associated with ALI/ARDS is lacking, and no specific drug therapy is available for ALI/ARDS. Therefore, in this study, biomarkers and signaling pathways associated with ALI/ARDS were summarized to provide a reference for future clinical and research work. A review of Traditional Chinese Medicine for the treatment or prevention of ALI/ARDS is also presented to provide a reference for further development of Traditional Chinese Medicine. In summary, this review will help raise awareness of ALI/ARDS and provide insight into the future exploitation of Traditional Chinese Medicine.

[The moderating effect analysis of mindfulness on perceived stress and job burnout of medical staff].

Objective: To explore the moderating mechanism of mindfulness on perceived stress and job burnout of medical staff. Methods: From November 2020 to March 2022, 1626 medical staff were investigated by questionnaires. Chinese Version Perceived Stress Scale (CPSS), Maslach Burnout Inventory-Human Service Survey (MBI-HSS) and Mindful Attention Awareness Scale (MAAS) were used to evaluate the perceived stress, three dimensions of job burnout[depersonalization (DP), emotional exhaustion (EE), personal accomplishment (PA) ], and mindfulness level of medical staff. The Spearman rank correlation analysis was used to analyze the correlation between mindfulness and perceived stress, job burnout of medical staff. And the SPSS PROCESS macro program was used to test the moderating effect of mindfulness on perceived stress and job burnout. Results: Among the 1626 medical staff, 57.38% had perceived stress with health risk (933/1626), and 63.84% (1038/1626) had job burnout, among them, with 618 (38.01%), 274 (16.85%), and 146 (8.98%) experiencing mild, moderate and severe job burnout, respectively. The scores of mindfulness among medical staff were significantly correlated with perceived stress and various dimensions of job burnout (EE, DP and PA) (r(s)=-0.155, -0.351, -0.315, 0.307, P<0.001). Mindfulness had a moderating effect between perceived stress and job burnout, which was achieved through three moderating pathways: perceived stress-mindfulness-EE, perceived stress-mindfulness-DP and perceived stress-mindfulness-PA (ΔR(2)=0.073, 0.06, 0.006, P<0.001) . Conclusion: Medical staff have a high level of job burnout, mindfulness plays a moderating role between perceived stress and job burnout. Specific measures can be taken to improve the level of mindfulness in medical staff, so as to prevent and alleviate job burnout of medical staff.

Pharmaceutical care of vascular dementia patients with drug-induced liver injury caused by the Compound Congrong Yizhi Capsules: a case report.

BACKGROUND: Drug-induced liver injury (DILI) is a newly discovered adverse drug reaction of Compound Congrong Yizhi Capsules (CCYC) in the treatment of vascular dementia (VD), and targeted pharmaceutical care is urgently needed to be explored. CASE REPORT: DILI was found in a patient who was admitted to the hospital with a diagnosis of VD after treatment with Compound Congrong Yizhi Capsules. According to the guidelines, the patient was initially treated with magnesium isoglycyrrhizinate injection. After 4 days, the clinical pharmacist monitored liver function: alanine aminotransferase (ALT): 153 IU/L, aspartate aminotransferase (AST): 160 IU/L, total bilirubin (TBil): 4.5 µmol/L, and alkaline phosphatase (ALP): 551 IU/L, which indicated that DILI was further aggravated. In addition, the increased blood pressure (156/65 mmHg) indicated the requirement to adjust the medication. Then, the hepatoprotective drugs were adjusted with reduced glutathione combined with ursodeoxycholic acid. After 12 days of treatment, the liver function was significantly improved, the clinical treatment was effective, and the blood pressure was controlled stably with no obvious adverse drug reactions. CONCLUSIONS: With pharmaceutical care guided by clinical pharmacists, the DILI caused by Compound Congrong Yizhi capsules could be reversed to improve the clinical outcome and avoid the occurrence of serious complications.

Palmitic acid of Musa Paradisiaca induces apoptosis through caspase-3 in human oral squamous cell carcinoma.

OBJECTIVE: Despite apoptosis processes being conserved, cancer cells have developed mechanisms to inhibit apoptosis by altering anti-apoptotic molecules or inactivating pro-apoptotic. The aim of this study was to determine the palmitic acid of Musa paradisiaca var. sapientum (L) Kunz (MP) stem extracts against human oral squamous cell carcinoma (hOSCC) through caspase-3. MATERIALS AND METHODS: Ethanol and ethyl acetate extracts of MP stem were analyzed by gas chromatography-mass spectrometry (GC-MS). Computerized models of chemically active compounds were used to predict anticancer activity. Cytotoxicity was evaluated in Artemia salina Leach and hOSCC (OM-1) culture at concentrations 100, 90, 80, 70, 60, 50, 40, 30, 20, and 10 µg/mL respectively. The expression level of caspase-3 on hOSCC was measured by enzyme-linked immunoassay (ELISA). RESULTS: We found seven chemically active compounds in the ethanol extract and 15 compounds in the ethyl acetate extract of MP stem. The major component was hexadecanoic acid of palmitic acid derivates, and this was predicted to have anticancer activities as apoptosis through caspase-3 stimulants. However, cytotoxicity effects against hOSCC culture were assessed by values of the 50% inhibitory concentration (IC50) of 15.00 µg/mL for the ethanol extract, and an IC50 of 10.61 µg/mL for the ethyl acetate. There was a significant increase of caspase-3 level on treatment groups compared to control. CONCLUSIONS: Hexadecanoic acid of MP stem extracts has anticancer activity by inhibiting cell growth of hOSCC culture through caspase-3 stimulants.

Effect of arginine supplementation on the production of milk fat in dairy cows.

Arginine, one of the conditionally essential AA, has been reported to affect fat synthesis and metabolism in nonruminant animals by influencing adenosine monophosphate activated protein kinase (AMPK) in some organs. In dairy cows, the effect of Arg on milk fat production is not clear, and any potential mechanism that underlies the effect is unknown. We tested the hypothesis that Arg infusion would improve the production of milk fat, and explored possible mechanism that might underlie any effect. We used 6 healthy lactating cows at 20 ± 2 d in milk, in fourth parity, with a body weight of 508 ± 14 kg, body condition score of 3.0 ± 0, and a milk yield of 30.6 ± 1.8 kg/d (mean ± standard deviation). The cows were blocked by days in milk and milk yield and each cow received 3 treatments in a replicated 3 × 3 Latin square design, with each of the experimental periods lasting 7 d with a 14-d washout between each period. The treatments, delivered in random order, were (1) infusion of saline (control); (2) infusion of 0.216 mol/d of l-Arg in saline (Arg); (3) infusion of 0.868 mol/d of l-Ala in saline (the Arg and Ala treatments were iso-nitrogenous) through a jugular vein. On the last day of each experimental period, blood was sampled to measure insulin, nitric oxide, glucose, and nonesterified fatty acid, and the liver and mammary gland were biopsied to measure the expression of genes. Milk yield was recorded, and milk fat percentage was measured daily during each of the experimental periods. The yield and composition of fatty acid (FA) in milk was measured daily on the last 3 d during each of the experimental periods. The data were analyzed using a mixed model with treatment as a fixed factor, and cow, period, and block as random factors. The daily milk yield and milk fat yield when the cows were infused with Arg were 2.2 kg and 76 g, respectively, higher than that in control, and 1.8 kg and 111 g, respectively, higher than that in Ala. When the cows were infused with Arg they had higher concentration and yield of de novo synthesized FA, than when they received the control or Ala infusions, although milk fat percentage, daily feed intake, and the digestibility of nutrients were not affected by treatment. The serum concentration of nitric oxide and insulin were higher during Arg than during control or Ala, with no difference between control and Ala. In the liver, the expression of the genes coding for AMPK (PRKAA1, PRKAB1, and PRKAG1) and genes related to the oxidation of FA were higher during Arg than during control or Ala, whereas in the mammary gland the expression PRKAB1 was lowest, and the expression of genes involved in the synthesis of milk fat were highest, during Arg infusion. The results suggest the intravenous infusion of Arg enhanced the production of milk fat by promoting the de novo synthesis of FA and increasing milk yield.

Nicotinamide riboside attenuates age-associated metabolic and functional changes in hematopoietic stem cells.

With age, hematopoietic stem cells (HSC) undergo changes in function, including reduced regenerative potential and loss of quiescence, which is accompanied by a significant expansion of the stem cell pool that can lead to haematological disorders. Elevated metabolic activity has been implicated in driving the HSC ageing phenotype. Here we show that nicotinamide riboside (NR), a form of vitamin B3, restores youthful metabolic capacity by modifying mitochondrial function in multiple ways including reduced expression of nuclear encoded metabolic pathway genes, damping of mitochondrial stress and a decrease in mitochondrial mass and network-size. Metabolic restoration is dependent on continuous NR supplementation and accompanied by a shift of the aged transcriptome towards the young HSC state, more youthful bone marrow cellular composition and an improved regenerative capacity in a transplant setting. Consequently, NR administration could support healthy ageing by re-establishing a more youthful hematopoietic system.

[A case of Hemolytic anemia caused by subacute lead poisoning].

Lead poisoning is characterized by nervous, digestive and blood system damage, such as neurasthenia, abdominal pain, abdominal distension, jaundice, small cell hypochromic anemia and so on. A case of severe hemolytic anemia caused by subacute lead poisoning was treated in Beijing Chaoyang Hospital Affiliated to Capital Medical University. The main symptoms of the patient were abdominal colic, constipation and hemolytic anemia.

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.

We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2. The MD involves temperature replica exchange enhanced sampling, making use of massively parallel supercomputing to quickly sample the configurational space of protein drug targets. Using the Summit supercomputer at the Oak Ridge National Laboratory, more than 1 ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to 10 configurations of each of the 24 SARS-CoV-2 systems using AutoDock Vina. Comparison to experiment demonstrates remarkably high hit rates for the top scoring tranches of compounds identified by our ensemble approach. We also demonstrate that, using Autodock-GPU on Summit, it is possible to perform exhaustive docking of one billion compounds in under 24 h. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and artificial intelligence (AI) methods to cluster MD trajectories and rescore docking poses.

Research Progress of Metabolomics in Forensic Pathology.

ABSTRACT: Metabolomics is an interdisciplinary subject that rose in the post-genomic era, which focuses on quantitative study of the response of living organisms to outside stimulation and pathophysiological changes, as well as multiple dynamic response of the level of in vivo metabolites caused by genetic mutation. It is extensively used in basic research of system biology, materia medica, clinical medicine, etc. In the forensic field, metabolomics mainly focuses on forensic toxicology, but with the generalization of certain techniques, it's foreseeable that metabolomics has a broad research prospect in forensic pathology. This article summarizes the major analysis techniques and methods of metabolomics, describes the research status of metabolomic techniques in the field of forensic pathology application research, including postmortem interval and death cause. Moreover, this article summarizes and discusses the potential applicable areas, in order to provide reference for relative research and application.

Effects of intravenous arginine infusion on inflammation and metabolic indices of dairy cows in early lactation.

Enhancing the supply of arginine (Arg), a semi-essential amino acid, has positive effects on immune function in dairy cattle experiencing metabolic stress during early lactation. Our objective was to determine the effects of Arg supplementation on biomarkers of liver damage and inflammation in cows during early lactation. Six Chinese Holstein lactating cows with similar BW (508 ± 14 kg), body condition score (3.0), parity (4.0 ± 0), milk yield (30.6 ± 1.8 kg) and days in milk (20 ± days) were randomly assigned to three treatments in a replicated 3 × 3 Latin square design balanced for carryover effects. Each period was 21 days with 7 days for infusion and 14 days for washout. Treatments were (1) Control: saline; (2) Arg group: saline + 0.216 mol/day l-Arg; and (3) Alanine (Ala) group: saline + 0.868 mol/day l-Ala (iso-nitrogenous to the Arg group). Blood and milk samples from the experimental cows were collected on the last day of each infusion period and analyzed for indices of liver damage and inflammation, and the count and composition of somatic cells in milk. Compared with the Control, the infusion of Arg led to greater concentrations of total protein, immunoglobulin M and high density lipoprotein cholesterol coupled with lower concentrations of haptoglobin and tumor necrosis factor-α, and activity of aspartate aminotransferase in serum. Infusion of Ala had no effect on those biomarkers compared with the Control. Although milk somatic cell count was not affected, the concentration of granulocytes was lower in response to Arg infusion compared with the Control or Ala group. Overall, the biomarker analyses indicated that the supplementation of Arg via the jugular vein during early lactation alleviated inflammation and metabolic stress.

Nutrient addition does not increase the benefits of clonal integration in an invasive plant spreading from open patches into plant communities.

One benefit of clonal integration is that resource translocation between connected ramets enhances the growth of the ramets grown under stressful conditions, but whether such resource translocation reduces the performance of the ramets grown under favourable conditions has not produced consistent results. In this study, we tested the hypothesis that resource translocation to recipient ramets may reduce the performance of donor ramets when resources are limiting but not when resources are abundant. We grew Mikania micrantha stolon fragments (each consisting of two ramets, either connected or not connected) under spatially heterogeneous competition conditions such that the developmentally younger, distal ramets were grown in competition with a plant community and the developmentally older, proximal ramets were grown without competition. For half of the stolon fragments, slow-release fertiliser pellets were applied to both the distal and proximal ramets. Under both the low and increased soil nutrient conditions, the biomass, leaf number and stolon length of the distal ramets were higher, and those of the proximal ramets were lower when the stolon internode was intact than when it was severed. For the whole clone, the biomass, leaf number and stolon length did not differ between the two connection treatments. Connection did not change the biomass of the plant communities competing with distal ramets of M. micrantha. Although clonal integration may promote the invasion of M. micrantha into plant communities, resource translocation to recipient ramets of M. micrantha will induce a cost to the donor ramets, even when resources are relatively abundant.

Nutrient, metal contents and microbiological properties of litter and soil along a tree age gradient in Mediterranean forest ecosystems.

The link among the age of aboveground tree species, litter, soil quality and status in Mediterranean forests is not entirely comprehended (especially in Mediterranean forest sites). This study evaluates whether and by what extent tree stand composition and forest structure modify nutrient depository or alter physical, chemical and microbiological properties of soil and litter in a 120 years old pine forest chronosequence. In general, the enzymatic activity related to the phosphorous, carbon and nitrogen cycles were more developed in litter than in soil surface, while the sulphur enzymatic activity was not significantly different between the two analyzed systems. The higher dehydrogenase content measured in the litter may be an index of a higher extracellular microbial activity, compared to soil. A noticeable effect of forest age and structure on the majority of analyzed elements was detected, with nutrients and metals tending to accumulate in soil rather in the litter. Moreover, the contents of P and some metals and sulphur enzymatic activity in the litter are influenced by forest age and associated forest structure. Finally, since nutrient, metals and enzyme contents in the litter increase with forest age, forest management strategies targeted to increase the stand structure may be advisable in order to achieve higher soil functionality.

Effect of pH on uranium(VI) biosorption and biomineralization by Saccharomyces cerevisiae.

Biosorption of radionuclides by microorganisms is a promising and effective method for the remediation of contaminated areas. pH is the most important factor during uranium biosorption by Saccharomyces cerevisiae because the pH value not only affects the biosorption rate but also affects the precipitation structure. This study investigated the effect of pH on uranium (VI) biosorption and biomineralization by S. cerevisiae. Cells have the ability to buffer the solution to neutral, allowing the biosorption system to reach an optimal level regardless of the initial pH value. This occurs because there is a release of phosphate and ammonium ions during the interaction between cells and uranium. The uranyl and phosphate ions formed nano-particles, which is chernikovite H2(UO2)2(PO4)2·8H2O (PDF #08-0296), on cell surface under the initial acidic conditions. However, under the initial alkaline conditions, the uranyl, phosphate and ammonium ions formed a large amount of scale-like precipitation, which is uramphite (NH4)(UO2)PO4·3H2O (PDF #42-0384), evenly over on cell surface.

Control of microbial sulfide production by limiting sulfate dispersal in a water-injected oil field.

Oil production by water injection often involves the use of makeup water to replace produced oil. Sulfate in makeup water is reduced by sulfate-reducing bacteria to sulfide, a process referred to as souring. In the MHGC field souring was caused by using makeup water with 4mM (384ppm) sulfate. Mixing with sulfate-free produced water gave injection water with 0.8mM sulfate. This was amended with nitrate to limit souring and was then distributed fieldwide. The start-up of an enhanced-oil-recovery pilot caused all sulfate-containing makeup water to be used for dissolution of polymer, which was then injected into a limited region of the field. Produced water from this pilot contained 10% of the injected sulfate concentration as sulfide, but was free of sulfate. Its use as makeup water in the main water plant of the field caused injection water sulfate to drop to zero. This in turn strongly decreased produced sulfide concentrations throughout the field and allowed a decreased injection of nitrate. The decreased injection of sulfate and nitrate caused major changes in the microbial community of produced waters. Limiting sulfate dispersal into a reservoir, which acts as a sulfate-removing biofilter, is thus a powerful method to decrease souring.

[Efficacy of Weitan Waifu patch on the postsurgical gastroparesis syndrome of gastrointestinal cancer: a multi-center trial].

Objective: To investigate the safety and efficacy of the Weitan Waifu patch on the postsurgical gastroparesis syndrome (PGS) of gastrointestinal cancer. Methods: The multi-center, double-blind, randomized controlled trial was conducted with superiority design. Patients with PGS of gastrointestinal cancer diagnosed in 4 AAA hospitals and the abdominal symptom manifested as cold syndrome by Chinese local syndrome differentiation were recruited. These patients were randomly divided into two groups according to 1∶1 proportion. Placebo or Weitan Waifu patch was applied in control group or intervention group, respectively, based on the basic treatments, including nutrition support, gastrointestinal decompression, promoting gastric dynamics medicine.Two acupuncture points (Zhongwan and Shenque) were stuck with placebo in control group or patch in treatment group. The intervention course was 14 days or reached the effective standard. Results: From July 15, 2013 to Jun 3, 2015, 128 participants were recruited and 120 eligible cases were included in the full analysis set (FAS), and 60 cases in each group. 88 cases were included in the per-protocol set (PPS), including 45 cases in the treatment group and 43 cases in the control group. In the FAS, the clinical effective rate in the treatment group was 68.3%, significantly superior than 41.7% of the control group (P=0.003). The medium time of effective therapy in the treatment group was 8 days, significantly shorter than 10 days in the control group (P=0.017). In the FAS, 3 adverse events occurred in the treatment group, including mild to moderate decrustation, pruritus and nausea. The incidence rate of adverse events was 5.0% (3/60) and these symptoms were spontaneously remitted after drug withdrawal. No severe adverse events were observed in the control group. There was no significant difference between these two groups (P=0.244). Conclusion: Weitan Waifu patch is a safely and effectively therapeutic method for patients with PGS (cold syndrome) of gastroenterological cancer. Trial registration: International Standard Randomized Controlled Trial Number Register, ISRCTN18291857.

High-intensity focused ultrasound and laparoscopic myomectomy in the treatment of uterine fibroids: a comparative study.

OBJECTIVE: To compare the clinical efficacies of high-intensity focused ultrasound (HIFU) and laparoscopic myomectomy (LM) in the treatment of uterine fibroids and their effects on patients' quality of life. DESIGN: A non-randomised control study. SETTING: Gynaecological department in a university teaching hospital. POPULATION: Patients with uterine fibroids. METHODS: From November 2014 to November 2015, 166 patients with uterine fibroids were enrolled and underwent HIFU (n = 99) and LM (n = 67) surgeries, respectively. Clinical efficacy, postoperative complications and quality of life after treatment were evaluated using the SF-36 Scale to compare the differences in each variable at the 1-year follow up. MAIN OUTCOMES MEASURES: Differences in efficacy, safety and quality of life between the patients treated with HIFU and LM. RESULTS: The 12-month follow-up results showed that the HIFU group had a total effective rate of 99%; only one patient underwent alternative treatment due to non-apparent tumour shrinkage. All patients in the LM group showed complete tumour disappearance. Of these patients, 52 showed significant clinical improvement, 15 with partial clinical improvement, a total effective rate of 98%. There was no significant difference in effectivity rate between the two groups (P > 0.05). Both treatments effectively improved patients' quality of life. Compared with the LM group, patients in the HIFU group experienced no blood loss, a shorter hospital stay and fewer adverse effects and complications, the difference being statistically significant (P < 0.05). CONCLUSIONS: High-intensity focused ultrasound can be as efficacious as LM therapy and effectively improve patients' quality of life in the treatment of uterine fibroids, with fewer adverse effects and complications, shorter hospital stays, and quicker postoperative recovery compared with LM therapy. TWEETABLE ABSTRACT: Patients with uterine fibroids can be effectively treated with both HIFU and myomectomy.

Surface Treatment on Physical Properties and Biocompatibility of Orthodontic Power Chains.

The conventional orthodontic power chain, often composed of polymer materials, has drawbacks such as a reduction of elasticity owing to water absorption as well as surface discoloration and staining resulting from food or beverages consumed by the patient. The goal of this study was to develop a surface treatment (nanoimprinting) for orthodontic power chains and to alleviate their shortcomings. A concave template (anodic alumina) was manufactured by anodization process using pure aluminum substrate by employing the nanoimprinting process. Convex nanopillars were fabricated on the surface of orthodontic power chains, resulting in surface treatment. Distinct parameters of the nanoimprinting process (e.g., imprinting temperature, imprinting pressure, imprinting time, and demolding temperature) were used to fabricate nanopillars on the surface of orthodontic power chains. The results of this study showed that the contact angle of the power chains became larger after surface treatment. In addition, the power chains changed from hydrophilic to hydrophobic. The power chain before surface treatment without water absorption had a water absorption rate of approximately 4%, whereas a modified chain had a water absorption rate of approximately 2%-4%. Furthermore, the color adhesion of the orthodontic power chains after surface modification was less than that before surface modification.

[Recurrent syncope related to catecholaminergic polymorphic ventricular tachycardia due to de novo RyR2-R2401H mutation].

Objective: To explore the clinical and molecular genetic features of a Chinese patient with catecholaminergic polymorphic ventricular tachycardia (CPVT). Methods: Clinical data including resting electrocardiography, echocardiography and treadmill exercise testing of a patient with CPVT admitted to our department in March 2013 were analyzed, and the peripheral venous blood samples of the patient and his family members and 400 ethnicity-matched healthy controls were obtained. All exons and exon-intron boundaries of the six CPVT-related genes including RYR2, CASQ2, TRDN, CALM1, KCNJ2 and ANKB were sequenced to detect the variants related to CPVT. The relationship between the genotypes and phenotypes was analyzed to direct the target therapy. Results: Recurrent syncope induced either by exercise or extreme frightened fear was observed in this patient. There was no positive family history of syncope or sudden death. The resting electrocardiography and echocardiography of the patient were normal, while the exercise testing revealed bidirectional and polymorphic ventricular tachycardia. A cardiac ryanodine receptor gene mutation (R2401H) was identified in this patient, while this mutation was absent in his parents and sister and 400 controls. No variant was detected in the remaining five candidate genes. Treatment with high dose of metoprolol succinate (118.75 mg/d) was effective and patient was free of syncopal attack during the 2 years follow-up. Conclusion: This is the first report on RyR2-R2401H mutation in Chinese patient with CPVT, and high dose of metoptolol is the effective therapy option for CPVT related to RyR2 mutation.

Loss of hypothalamic corticotropin-releasing hormone markedly reduces anxiety behaviors in mice.

A long-standing paradigm posits that hypothalamic corticotropin-releasing hormone (CRH) regulates neuroendocrine functions such as adrenal glucocorticoid release, whereas extra-hypothalamic CRH has a key role in stressor-triggered behaviors. Here we report that hypothalamus-specific Crh knockout mice (Sim1CrhKO mice, created by crossing Crhflox with Sim1Cre mice) have absent Crh mRNA and peptide mainly in the paraventricular nucleus of the hypothalamus (PVH) but preserved Crh expression in other brain regions including amygdala and cerebral cortex. As expected, Sim1CrhKO mice exhibit adrenal atrophy as well as decreased basal, diurnal and stressor-stimulated plasma corticosterone secretion and basal plasma adrenocorticotropic hormone, but surprisingly, have a profound anxiolytic phenotype when evaluated using multiple stressors including open-field, elevated plus maze, holeboard, light-dark box and novel object recognition task. Restoring plasma corticosterone did not reverse the anxiolytic phenotype of Sim1CrhKO mice. Crh-Cre driver mice revealed that PVHCrh fibers project abundantly to cingulate cortex and the nucleus accumbens shell, and moderately to medial amygdala, locus coeruleus and solitary tract, consistent with the existence of PVHCrh-dependent behavioral pathways. Although previous, nonselective attenuation of CRH production or action, genetically in mice and pharmacologically in humans, respectively, has not produced the anticipated anxiolytic effects, our data show that targeted interference specifically with hypothalamic Crh expression results in anxiolysis. Our data identify neurons that express both Sim1 and Crh as a cellular entry point into the study of CRH-mediated, anxiety-like behaviors and their therapeutic attenuation.

Effects of Dietary Supplementation of ß-hydroxy-ß-methylbutyrate on Sow Performance and mRNA Expression of Myogenic Markers in Skeletal Muscle of Neonatal Piglets.

The effects of dietary ß-hydroxy-ß-methylbutyrate (HMB) supplementation during gestation on reproductive performance of sows and the mRNA expression of myogenic markers in skeletal muscle of neonatal pigs were determined. At day 35 of gestation, a total of 20 sows (Landrace × Yorkshire, at third parity) were randomly assigned to two groups, with each group receiving either a basal diet or the same diet supplemented with 4 g/day ß-hydroxy-ß-methylbutyrate calcium (HMB-Ca) until parturition. At parturition, the total and live litter size were not markedly different between treatments, however, the sows fed HMB diet had a decreased rate of stillborn piglets compared with the sows fed the control (CON) diets (p < 0.05). In addition, piglets from the sows fed HMB diet tended to have an increased birth weight (p = 0.08), and a reduced rate of low birth weight piglets (p = 0.05) compared with piglets from the CON sows. Nevertheless, lower feed intake during lactation was observed in the sows fed the HMB diet compared with those on the CON diet (p < 0.01). The relative weights of the longissimus dorsi (LD) and semitendinosus (ST) muscle were higher (p < 0.05) in neonatal pigs from the HMB than the CON sows. Furthermore, maternal HMB treatment increased the mRNA levels of the myogenic genes, including muscle regulatory factor-4 (MRF4, p < 0.05), myogenic differentiation factor (MyoD) and insulin-like growth factor-1 (IGF-1, p < 0.01). In conclusion, dietary HMB supplementation to sows at 4 g/day from day 35 of gestation to term significantly improves pregnancy outcomes and increases the expression of myogenic genes in skeletal muscle of neonatal piglets, but reduces feed intake of sows during lactation.