Short-term exposure to noise on stroke volume and left ventricular contractility: A repeated-measure study.

Prolonged exposure to noise has been associated with cardiovascular disease, but the possible mechanism for its influence on cardiac activity is unknown. This study investigated the acute effects of noise exposure on 24-h ambulatory cardiac parameters among male workers. We recruited 75 volunteers in an aviation-industry cohort in 2009. Personal noise-exposure levels and individual cardiac parameters, including stroke volume (SV) and left ventricular contractility (LVC), were measured simultaneously over 24 h on working and nonworking days. Linear mixed-effects regression models were used to estimate transient and sustained effects on ambulatory SV and LVC among high-noise-exposure (≥80 A-weighted decibels [dBA]), low-noise-exposure (<80 dBA) and office workers. Every 1-dBA increase in noise exposure was significantly associated with transient changes of -1.50 (95% confidence interval [CI]: -2.18, -1.03) ml/beat in SV and -1.76 (-2.99, -1.03) L/sec in LVC at work on working days only among high-exposure workers. The 1-dBA increase in nocturnal noise exposure was also significantly associated with transiently decreased SV among high-exposure (-1.62 [-2.15, -1.22] ml/beat), low-exposure (-1.27 [-1.57, -1.03] ml/beat) and office workers (-1.09 [-1.18, -1.00] ml/beat), but only the high-exposure group had the transiently reduced LVC (-1.70, [-2.37, -1.22] L/sec) after the current noise exposure on nonworking days. Such decreasing effects persisted to become sustained decreases in 24-h ambulatory SV in high-exposure (-1.10 [-1.20, -1.01] ml/beat) and office workers (-1.13 [-1.22, -1.05] ml/beat) on working days and in all three groups (-1.19 [-1.36, -1.04]; -1.15 [-1.31, -1.02]; -1.08 [-1.13, -1.02] ml/beat, respectively) on nonworking days. No significant effect on 24-h ambulatory LVC was found in any group on working or nonworking days. Occupational and nocturnal noise exposure may have acute effects on 24-h ambulatory SV among male workers, directly influencing the cardiac function related to cardiovascular disease.

Overexpression of Androgen, Oestrogen and Progesterone Receptors in Skin Lesions of Becker's Naevus.

Becker's naevus is androgen-dependent. The aim of this study was to investigate whether oestrogen and progesterone receptors are involved in this disorder. Immunohistochemistry showed that epidermal expression of androgen receptors, oestrogen receptors (α, ß) and progesterone receptors was higher in skin lesions of Becker's naevus than in perilesional and control skin. Androgen receptor overexpression was observed in pilosebaceous glands, while oestrogen and progesterone receptor overexpression was seen in hair follicles, but not in sebaceous glands in skin lesions compared with perilesional skin. Reverse tran-scription PCR and Western blot revealed that levels of androgen, oestrogen and progesterone receptors were generally upregulated in skin lesions compared with perilesional and control skin, and their expression was usually higher in perilesional than in control skin. These results suggest that simultaneous overexpression of androgen, oestrogen and progesterone receptors might be implicated in the pathogenesis of Becker's naevus.

[Current Status and Challenges of CAR-T Immunotherapy in Hematologic Malignancies -Review].

The chimeric antigen receptor (CAR) T cell therapy has gradually became a new trend in the treatment of refractory and relapsed hematologic malignancies by developing for 30 years. With the exciting development of genetic engineering, CAR-T technology has subjected to 4 generations of innovation. Structure of CAR-T started from a single signal molecule to 2 or more than 2 co-stimulatory molecules, and then coding the CAR gene or promoter. CAR-T can specifically recognize tumor antigens, and does not be restricted by major histocompatibility complex (MHC), thus making a breakthrough in clinical treatment. In this review, the history, structure and mechanism of action of CAR-T, as well as the current status and challenges of CAR-T immunotherapy in acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia and multiple myeloma are summarized.

Protective roles and mechanisms of polysaccharides from Dendrobium officinal on natural aging-induced premature ovarian failure.

This study was designed to investigate the pharmacological effects and mechanisms of polysaccharides from Dendrobium officinal (DOP) on premature ovarian failure (POF) in natural aging mice. Fifteen months old female mice (n  =  28) and young adult female mice (n  =  14, 6 weeks) were used. DOP (70 mg/kg) was administrated to mice by oral gavage for 10 weeks and the protection effects of DOP on ovaries were investigated in vivo. The results showed that DOP reduced body weight, ovary and uterus/body weight parameters to normal level and alleviated ovarian pathological damage. Moreover, DOP could reduce pro-inflammatory cytokines (TNF-α, IL-6) and MDA levels and improve estradiol, SOD, GSH-Px, T-AOC and IL-10 levels in serum. These results suggested that DOP may alleviate the damage caused by aging through the inhibition of the nuclear factor -κB (NF-κB) and p53/Bcl-2-mediate signaling pathways. Moreover, we found that DOP can increase the numbers of mitochondria and endoplasmic reticulum. Moreover, DOP increased the numbers of different stages of follicular cells and improved mitochondrial membrane potential in ovaries. These results indicated that DOP may relieve ovarian damage through the protection of mitochondria in the ovaries. These findings suggest that DOP may be a promising drug for treating POF caused by natural aging in females.

Overexpression of NLRP3, NLRC4 and AIM2 inflammasomes and their priming-associated molecules (TLR2, TLR4, Dectin-1, Dectin-2 and NFκB) in Malassezia folliculitis.

The activation of NLRP3, NLRC4 and AIM2 inflammasomes is pivotal for innate immunity against some pathogenic fungi, but their role in the pathogenesis of Malassezia folliculitis (MF) remains unclear. The objective of the study was to determine the expression of 4 canonical inflammasomes (NLRP1, NLRP3, NLRC4 and AIM2) and their priming-associated molecules (TLR2, TLR4, Dectin-1, Dectin-2 and NFκB) in MF lesion. Expression of NLRP1, NLRP3, NLRC4, AIM2, caspase-1, IL-1ß, TLR2, TLR4, Dectin-1, Dectin-2 and NFκB was detected by immunohistochemistry in skin lesion of 23 MF patients and normal skin of 12 healthy subjects. Furthermore, NLRP1, NLRP3, NLRC4, AIM2, caspase-1 and IL-1ß mRNA was measured by quantitative real-time PCR (qRT-PCR) in 12 MF cases and 10 controls. Immunohistochemical analysis revealed that NLRP3, NLRC4, AIM2, Casp-1, IL-1ß, TLR2, TLR4, Dectin-1, Dectin-2 and NFκB expression was up-regulated in the epidermis and dermal inflammatory cells of MF lesion compared with control skin (P < .01-.05), but NLRP1 expression was not different between both groups (P > .05). qRT-PCR showed that levels of NLRP3, Casp-1 and IL-1ß mRNA were significantly increased (P < .01-.05), whereas those of NLRP1, NLRC4 and AIM2 mRNA were slightly augmented compared to control skin (P > .05). Our observation suggests that simultaneous activation of NLRP3, NLRC4 and AIM2 inflammasomes may play an important role in the pathogenesis of MF.

Evaluation of toxicity studies of flavonoid fraction of Lithocarpus polystachyus Rehd in rodents.

The aim of the study was to evaluate the safety of flavonoid fraction of Lithocarpus polystachyus Rehd (Sweet Tea-F, ST-F) in mice and rats through acute and sub-chronic toxicity studies respectively. For acute toxicity study, a single dose of 5000 mg/kg of ST-F was given orally to healthy KM mice. The mice were observed mortality and toxic symptoms for 24 h, then once a day up to 14 days. In the sub-chronic toxicity study, ST-F was administered orally at doses of 0, 70, 140, 560 mg/kg/day to rats for 26 weeks. Body weight and food intake were recorded weekly. Hematological, biochemical, coagulation and organ parameters were analyzed at the end of 26 weeks administration. Vital organs were evaluated by histopathology. In the acute toxicity study, ST-F caused neither significant toxic symptoms, nor mortality in mice. In sub-chronic toxicity study, daily oral administration of ST-F at the dose of 70 mg/kg resulted in a significant increase (P < 0.05) in the relative body weight at the 10-week, and the same situation brought at the dose of 140 mg/kg/day at the 22-week. Hematological and biochemical showed significant changes (P < 0.01 or P < 0.05) in WBC, GLU, ALP, AST and serum electrolytes levels at the dose of 560 mg/kg/day. The amount of RBC decreased significantly (P < 0.05) while the content of PLT slightly increased (P < 0.05) at the dose of 140 mg/kg/day. In additional, no obvious histological changes were observed in vital organs of ST-F treated animals compared to control group. The ST-F may be exit slight side effects at the dose of 560 mg/kg/day in rats. Thus, the overall results show that the no-observed adverse effect level (NOAEL) of ST-F was considered to be 140 mg/kg for male SD rats.

In Situ Bioorthogonal Metabolic Labeling for Fluorescence Imaging of Virus Infection In Vivo.

Optical fluorescence imaging is an important strategy to explore the mechanism of virus-host interaction. However, current fluorescent tag labeling strategies often dampen viral infectivity. The present study explores an in situ fluorescent labeling strategy in order to preserve viral infectivity and precisely monitor viral infection in vivo. In contrast to pre-labeling strategy, mice are first intranasally infected with azide-modified H5N1 pseudotype virus (N3 -H5N1p), followed by injection of dibenzocyclooctyl (DBCO)-functionalized fluorescence 6 h later. The results show that DBCO dye directly conjugated to N3 -H5N1p in lung tissues through in vivo bioorthogonal chemistry with high specificity and efficacy. More remarkably, in situ labeling rather than conventional prelabeling strategy effectively preserves viral infectivity and immunogenicity both in vitro and in vivo. Hence, in situ bioorthogonal viral labeling is a promising and reliable strategy for imaging and tracking viral infection in vivo.

Effect of Dendrobium officinale on D-galactose-induced aging mice.

OBJECTIVE: To examine the effect of Dendrobium officinale (DO) on D-galactose-induced aging mice. METHODS: Aging mice was induced by D-galactose at 0.125 g/kg for 10 weeks through subcutaneous injection except for the negative control group. After 10 days, according to complete random design, the aging modeling mice were randomized into 4 groups: aging control group (10 ML·kg-1·d-1) of distilled water), positive control group (vitamin B6 and ganodema lucidum tablets with a dose of 1 tablet/kg), DO-1 treatment group (DO juice with a dose of 1 g/kg), DO-2 treatment group (DO Polysaccharide with a dose of 0.32 g/kg), 14 mice in each group. All the animals were orally medicated daily for 9 weeks. Cognitive function assessment was performed using the maze test and step-down test. At the end of experiment, the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) levels in the serum, the SOD, GSH-Px and nitric oxide (NO) levels in the cerebrum, the SOD and catalase (CAT) levels in the liver, the SOD and NO levels in the heart, and the SOD level in the kidney, were determined using commercial kits. The spleen, liver, heart, cerebrum and kidney were excised for histological study. RESULTS: Compared to aging control group, DO shortened the time of passing through the maze and prolong the step-down latency of aging mice (P <0.05 or P<0.01). DO markedly up-regulated serum levels of SOD, GSH-Px and T-AOC, and restored SOD levels in the heart, liver, kidney and cerebrum to normal status (P<0.05 or P<0.01). DO at the dose of 1 g/kg also signififi cantly improved the degree of spleen lesions (P<0.01). CONCLUSIONS: DO had marked anti-aging effect on D-galactose-induced model of aging. The underlying mechanism could be related to modulation on antioxidation system and immune system. The results indicated that DO could potentially be used as natural drugs or functional foods for preventing aging.

Dendrobium officinale Prevents Early Complications in Streptozotocin-Induced Diabetic Rats.

Background. Dendrobium officinale (DO) Kimura et Migo is a precious Chinese herb that is considered beneficial for health due to its antioxidant and antidiabetes properties, and so on. In this research, we try to determine the preventive effect of DO on the early complications of STZ-induced diabetic rats. Methods. Type 1 diabetic rats were produced with a single intraperitoneal injection of STZ (50 mg/kg). DO (1 g/kg/day) was then orally administered for 5 weeks. Blood glucose, TC, TG, BUN, CREA, and GSH-PX levels were determined, and electroretinographic activity and hypoalgesia were investigated. Pathological sections of the eyes, hearts, aortas, kidneys, and livers were analyzed. Results. Treatment with DO significantly attenuated the serum levels of TC, TG, BUN, and CREA, markedly increased the amplitudes of ERG a- and b-waves and Ops, and reduced the hypoalgesia and histopathological changes of vital organs induced by hyperglycemia. The protective effect of DO in diabetic rats may be associated with its antioxidant activity, as evidenced by the marked increase in the serum level of glutathione peroxidase. However, DO had no significant effect on blood glucose levels and bodyweight of diabetic rats. Conclusions. DO supplementation is an effective treatment to prevent STZ-induced diabetic complications.

[Transcriptome profiling and analysis of Panax japonicus var. major].

The rhizome of Panax japonicus var. major have been used as the natural medicinal agent by Chinese traditional doctors for more than thousand years. Most of the therapeutic effects of P. japonicus var. major had been reported due to the presence of tetracyclic or pentacyclic triterpene saponins. In this study, Illumina pair-end RNA-sequencing and de novo splicing were done in order to understand the pathway of triterpenoid saponins in this species. The valid reads data of 15. 6 Gb were obtained. The 62 240 unigenes were finally obtained by de novo splicing. After annotation, we discovered 19 unigenes involved in ginsenoside backbone biosynthesis. Additionally, 69 unigenes and 18 unigenes were predicted to have potential function of cytochrome P450 and UDP-glycosyltransferase based on the annotation results, which may encode enzymes responsible for ginsenoside backbone modification. This study provides global expressed datas for P. japonicus var. major, which will contribute significantly to further genome-wide research and analysis for this species.

Report: structures and hepatocytotoxicity of co-occurring substances in oleanolic acid tablets.

Tablets of oleanolic acid (OA) have been approved by SFDA in China as an adjuvant therapy for acute and chronic hepatitis. Co-occurring substances present in the tablets of OA and their hepatocytotoxicity have not yet been reported. In the current investigation, the crude OA drug was separated by repeated column chromatography. The structures of the isolated compounds were characterized by spectral analysis and the cytotoxicity of each compound was evaluated in vitro against the human normal liver cell L02 at concentrations from 0.125 to 1000 µmol/L using the MTT method. As a result, OA and its 11 co-occurring trace compounds including one new triterpenoid, 3-O- (4-oxo-pentanoyl)-olean-12- en-28-oic acid, were isolated and structurally characterized. Cytotoxicity tests indicated that these compounds were all non-toxic at concentrations up to 50µmol/L. Clear structure-activity relationship (SAR) was also observed. The results suggested that OA tablets of similar origin might not cause obvious cytotoxicity to the normal liver cell. The work may facilitate further SAR studies of OA-type triterpenoids.

[Effects of blueberry on the proliferation and activation of hepatic stellate cell and its mechanism].

OBJECTIVE: To investigate the effects of blueberry on the proliferation and activation of hepatic stellate cell (HSC) and its mechanism. METHODS: Rat HSC were isolated by type IV collagenase digestion and Nycodenz density gradient centrifugation. The cultured HSC was incubated at different concentrations of 10% blueberry serum. The 10% DSHX serum was used as positive control and 10% normal rat serum group as control. MTT colorimetric assay was used to detect the HSC proliferation. ColI of culture supernatant was detected by ELISA. The expression of α-SMA in HSC was measured by immunocytochemistry staining while the expressions of Nrf2 and HO-1 were determined by Western blot. RESULTS: Compared with controls, the low and high-dose blueberry serum groups significantly inhibited the HSC proliferation (P < 0.05). It had the same inhibitory effects as the positive control serum group (P > 0.05). ColI of culture supernatant obviously decreased (P < 0.05). And the expression levels of α-SMA in low and high-dose blueberry serum groups decreased significantly (P < 0.05). And there were similar effects in low & high-dose blueberry serum and positive control serum groups. Western blot showed that the expressions of Nrf2 and HO-1 in blueberry and positive control serum groups were higher than that in control group. And the increment was more significant in the low and high-dose blueberry serum groups (P < 0.05). CONCLUSION: Blueberry can significantly inhibit the proliferation and activation of HSC and reduce the synthesis of extra-cellular matrix. It may have potential preventive and protective effects on hepatic fibrosis. The mechanism may be related to an elevated expression of HO-1 through the Nrf2 pathway.