Ozonated oil alleviates dinitrochlorobenzene-induced allergic contact dermatitis via inhibiting the FcεRI/Syk signaling pathway / 中南大学学报(医学版)

OBJECTIVES@#Ozone is widely applied to treat allergic skin diseases such as eczema, atopic dermatitis, and contact dermatitis. However, the specific mechanism remains unclear. This study aims to investigate the effects of ozonated oil on treating 2,4-dinitrochlorobenzene (DNCB)-induced allergic contact dermatitis (ACD) and the underling mechanisms.@*METHODS@#Besides the blank control (Ctrl) group, all other mice were treated with DNCB to establish an ACD-like mouse model and were randomized into following groups: a model group, a basal oil group, an ozonated oil group, a FcεRI-overexpressed plasmid (FcεRI-OE) group, and a FcεRI empty plasmid (FcεRI-NC) group. The basal oil group and the ozonated oil group were treated with basal oil and ozonated oil, respectively. The FcεRI-OE group and the FcεRI-NC group were intradermally injected 25 µg FcεRI overexpression plasmid and 25 µg FcεRI empty plasmid when treating with ozonated oil, respectively. We recorded skin lesions daily and used reflectance confocal microscope (RCM) to evaluate thickness and inflammatory changes of skin lesions. Hematoxylin-eosin (HE) staining, real-time PCR, RNA-sequencing (RNA-seq), and immunohistochemistry were performed to detct and analyze the skin lesions.@*RESULTS@#Ozonated oil significantly alleviated DNCB-induced ACD-like dermatitis and reduced the expressions of IFN-γ, IL-17A, IL-1β, TNF-α, and other related inflammatory factors (all P<0.05). RNA-seq analysis revealed that ozonated oil significantly inhibited the activation of the DNCB-induced FcεRI/Syk signaling pathway, confirmed by real-time PCR and immunohistochemistry (all P<0.05). Compared with the ozonated oil group and the FcεRI-NC group, the mRNA expression levels of IFN-γ, IL-17A, IL-1β, IL-6, TNF-α, and other inflammatory genes in the FcεRI-OE group were significantly increased (all P<0.05), and the mRNA and protein expression levels of FcεRI and Syk were significantly elevated in the FcεRI-OE group as well (all P<0.05).@*CONCLUSIONS@#Ozonated oil significantly improves ACD-like dermatitis and alleviated DNCB-induced ACD-like dermatitis via inhibiting the FcεRI/Syk signaling pathway.

ADP-ribosylhydrolases: from DNA damage repair to COVID-19 / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Adenosine diphosphate (ADP)-ribosylation is a unique post-translational modification that regulates many biological processes, such as DNA damage repair. During DNA repair, ADP-ribosylation needs to be reversed by ADP-ribosylhydrolases. A group of ADP-ribosylhydrolases have a catalytic domain, namely the macrodomain, which is conserved in evolution from prokaryotes to humans. Not all macrodomains remove ADP-ribosylation. One set of macrodomains loses enzymatic activity and only binds to ADP-ribose (ADPR). Here, we summarize the biological functions of these macrodomains in DNA damage repair and compare the structure of enzymatically active and inactive macrodomains. Moreover, small molecular inhibitors have been developed that target macrodomains to suppress DNA damage repair and tumor growth. Macrodomain proteins are also expressed in pathogens, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, these domains may not be directly involved in DNA damage repair in the hosts or pathogens. Instead, they play key roles in pathogen replication. Thus, by targeting macrodomains it may be possible to treat pathogen-induced diseases, such as coronavirus disease 2019 (COVID-19).

New thoughts in mechanism research of acupuncture for myocardial stunning from κ-opioid receptor signaling pathway / 中国针灸

By reviewing the literature regarding the development mechanism of myocardial stunning, effects of acupuncture on myocardial ischemic injury, and correlation between acupuncture and κ-opioid receptor, it was suggested that acupuncture was highly likely to act on κ-opioid receptor in myocardial cells, and directly treated myocardial malfunction induced by myocardial stunning through κ-opioid receptor and its signaling pathway. In addition, acupuncture could inhabit the signaling pathway of adrenoceptor β1, one of the main functional receptors, to indirectly improve myocardial ischemic injury. From κ-opioid receptor signaling pathway, the action mechanism of acupuncture for prevention and treatment of myocardial stunning was discussed in this paper, hoping to provide new ideas for possible mechanism of acupuncture for myocardial ischemic injury.

Discussion on specificity of acupoint effect based on "acupoint fordiseases" / 中国针灸

The specificity of acupoint effect is an important part of acupuncture theory. It has been one of the foci in acupuncture research domestically and abroad. This paper explores the specific relationship between Zusanli (ST 36) and stomach-intestine function based on the ancient records on "acupoint fordiseases" and the clinical and experimental researches on Zusanli(ST 36) treating digestive diseases. The physiological mechanism of the specificity is explained in terms of the spinal cord segment of Zusanli (ST 36) and gastrointestinal organs as well as the cerebral central effect of puncturing the acupoint. The aim of the paper is to provide more evidences for the specificity of acupoint effect indicated by "acupoint fordiseases".

Protective effects of adipose?derived stem cells with phosphodiesterase 5 inhibition by lentivirus?mediated stable gene silencing on ischemia?reperfusion injury of renal tubular epithelial cells / 中华肾脏病杂志

Objective To explore the protective effects of adipose - derived stem cells (ADSCs) with phosphodiesterase 5 inhibition by lentivirus-mediated stable gene silencing on the proliferation and apoptosis of renal tubular epithelial cells induced by ischemia-reperfusion injury in vitro. Methods To isolate cultivate and indentify ADSCs from rats. Lentiviral expression vector of carrying PDE5 shRNA gene was transfected into ADSCs, and a negative control group was set up.Western blotting was used to detect PDE5 protein expression levels. ADSCs were co-cultured with NRK-52E in a transwell system, and NRK-52E cells were treated with ischemia/reoxygenation protocol. Edu assay was performed to evaluate the proliferation of NRK cells, flow cytometry to detect the apoptosis of NRK cells, and ELISA to quantify the protein expressions of fibroblast growth factor (FGF) and hepatocyte growth factor (HGF). The expression of E - cadherin and cytokeratin 18 (CK18) was quantified by real time PCR and flow cytometry. Results Western blotting for PDE5 protein indicated a significant reduction of PDE5 protein levels in PDE5 shRNA transduced population. After the treatment of ischemia/reoxygenation in vitro, the proliferative viability and apoptosis of NRK-52E cells co-cultured with ADSCs induced by PDE5 gene inhibition were significantly improved, compared to the normal group (all P<0.05). And the release of HGF, FGF were markedly enhanced (all P<0.05). Moreover, the NRK-52E cells survival, the expression of E-cadherin and CK18 on PDE5 inhibited ADSCs co-cultured with I/R injured NRK cells was significantly increased compared to that in the negative control group (all P<0.05). Conclusion ADSCs preconditioned by inhibition of PDE5 can be a powerful novel approach to improve the survival of renal tubular cells following ischemia-reperfusion injury, and have an obvious tendency to transform epithelial cells.

Entity of acupoint: kinetic changes of acupoints in histocytochemistry / 中国针灸

The present study aims to investigate the kinetic histocytochemical changes of acupoints in different condition. The expression of tryptase (+) mast cells, histamine (HA) , serotonin (5-HT) and nociceptive neuropeptides including calcitonin gene-related peptide (CGRP) and substance P (SP) were observed by immunohistochemistry combined with confocal technology. Mast cells were labeled with anti-mast cell tryptase antibody and simultaneously with HA or 5-HT primary antibodies to observe their co-expression. The results showed that: (1) SP and CGRP were expressed more highly on the cutaneous nerve fibers of "Hegu" (LI 4) after acupuncture stimulation than that of the control. Mast cells aggregated in close proximity to the blood vessels in intra-epidermis and dermis, and some of them with degranulation in the lower dermis and subcutaneous tissue of "Hegu" (LI 4). Both mast cells and their granules appeared with HA (+) and 5-HT (+) expression at stimulated LI 4 sites, while a few intact mast cells with a little expression of 5-HT and HA were distributed in areas of non-stimulated Ll 4. (2) The acupoints in different locations such as Baihui (GV 20), Weishu (BL 21), Zhongwan (CV 12) and LI 4 had the same constituent but the contents were different. (3) The histocytochemical responses of acupoints sensitized by the Gastric mucosa injury (GMI) were also investigated. GMI resulted in neurogenic plasma extravasation by Evans Blue (EB) in the skin of the acupoints over the back and abdomen, which mostly occurred in the T9-T11 dermatomere. The EB extravasation dots just like acupoints sensitization appeared after GMI and disappeared gradually during the natural self-recovery of the gastric mucosa. More SP and CGRP positive nerve fibers were distributed in EB dots than in regions beside EB dots and in the control, mostly distributed in the nerve fibers around both the vessels and root of hair follicle. Mast cells also aggregated and degranulated to release algogenic substances of 5-HT and HA around the vessels in areas of the EB dots. Collectively the acupoints displayed the same histocytochemical responses due to either acupuncture stimulation or GMI. This may potentially be the histocytochemical basis in the local acupoints and acupoints displayed kinetic changes in different condition.

Compairison between western and Chinese acupuncture and its enlightenment / 中国针灸

With the wide application of acupuncture in the world, the research results of neurosciences have made scientific approval on some of efficacy and mechanism of acupuncture, and the concept of western medical acupuricture (WMA) is gradually developed. During the spread of Chinese acupuncture into western countries, WMA is an adaptive improvement when facing basic theories of western medicine including anatomy, physiology and pathology as well as evidence-based medicine system. WMA which is based on theory of muscle trigger point has obvious efficacy on muscular fasciae pain, which attracted wide attention. But when Chinese acupuncture spreads into western world, the theories of Chinese acupuncture such as meridian and specificity of acupoint are questioned due to the results of western clinical study. In this paper, the origin, theory development, stimulating location and method, and categories of diseases of WMA are compared with Chinese acupuncture, and the enlightenment of this difference on Chinese acupuncture research is analyzed.

Influence of Different Fixing Methods on Cardiac Index in C57 Mice of Wild Type andβ-adrenoceptor Knockout Mice / 世界科学技术-中医药现代化

This study was aimed to choose the best fixing method of electrocardiogram (ECG) measurement in mice by comparison of ECG index in three different fixing ways. Changes of ST amplitude and heart rate in ECG were measured in the self-made mouse sets, tape bundling or breathing anesthesia state. The amplitudes of the ST seg-ment in C57BL6 mice and β1/β2-AR double knockout mice were elevated in tape bundling or breathing anesthesia state in comparison with that in the self-made mouse sets (all P < 0.01). The heart rate under the tape bundling state in C57BL6 mice was significantly faster than that in the self-made mouse sets (P< 0.05 or P< 0.01). And the heart rate under anesthesia in β1/β2-AR double knockout mice was significantly slower than that in tape bundling state or the self-made mouse sets (both P < 0.01). It was concluded that relative to the binding and anesthesia method, fixing mouse in the self-made mouse sets, which can more truly reflect the physiological or pathological states, is a relatively good fixing method of ECG measurement in experimental study.

New idea of treatment of heart failure with traditional Chinese medical / 中国中药杂志

To discuss the potential role of medicinal herbs, especially those with effect of strengthening Qi, in the treatment of chronic heart failure (CHF) via modulating myocardial substrate metabolism. The relationships among heart failure, myocardial energetic metabolism and herbal medicine were analyzed in detail through reviewing and summarizing the accumulating knowledge and recent findings on myocardial metabolism, heart failure and herbal medicine. Either energy lack or abnormal energetic metabolism is one of the main causes to the initiation and development of heart failure. Recent studies suggest that the cardiac function in the patients with CHF could be improved by inhibiting the energy production from metabolism of fatty acid and enhancing the energy production from glucose metabolism. The concept of Qi in Chinese medicine is very close to the energy in western medicine. The decoction of Chinese medicine containing herbal medicine with effect of strengthening Qi and the herbal medicine themselves and their components were evidenced to be effective in improvement of heart failure and regulation of both lipid and glucose metabolism; more importantly, all these herbal medicine contain the multi-sugar which can be metabolized into single unit of sugar which may be metabolized as a substrate by myocardium and potentially produce the cardioprotective effect. Therefore, we may find out a novel way to explain why the herbal medicine with effect of strengthening Qi can improve cardiac function in patients with CHF. In other words, regulating myocardial metabolism is one of the mechanisms underlying the cardioprotection produced by herbal medicine with effect of strengthening Qi in the treatment of heart failure.

The role of BRCA1 in DNA damage response

BRCA1 is a well-established tumor suppressor gene, which is frequently mutated in familial breast and ovarian cancers. The gene product of BRCA1 functions in a number of cellular pathways that maintain genomic stability, including DNA damage-induced cell cycle checkpoint activation, DNA damage repair, protein ubiquitination, chromatin remodeling, as well as transcriptional regulation and apoptosis. In this review, we discuss recent advances regarding our understanding of the role of BRCA1 in tumor suppression and DNA damage response, including DNA damage-induced cell cycle checkpoint activation and DNA damage repair.

Rapid Identification of Staphylococcus aureus and Its Resistance Against Meticillin Using Slidex-staph Monoclonal Antibody / 中华医院感染学杂志

OBJECTIVE To develop a rapid method for simultaneously identifying Staphylococcus aureus(SA) and its resistance against meticillin. METHODS The target strains authenicated to Staphylococcus by traditional methods(appearance,Gram-stain,catalase) first,then using Slidex~staph.plus to authenticate SA;establishing traditional method or coagulase test and ATB-ID32STAPH system for verification.The penicillin-binding protein 2a(PBP2a) was examined by Slidex MRSA Detection,establishing resistance oxacillin sieving test and mecA gene was examined by PCR for verification. RESULTS The 135 strains were positive and 321 strains were negative for Slidex~staph.plus from 456 strains.The 127 S.aureus strains and eight others were confirmed from 135 positive strains finally,11 SA strains and 310 other strains were confirmed from 321 negative strains,there were 92.0% for sensitivity and 97.5% for specificity in this method.The 52 strains PBP2a positively confirmed to meticillin-resistant S.aureus(MRSA) using Slidex MRSA Detection and 57 MRSA strains were confirmed using resistance oxacillin sieving test or PCR from 138 strains.There were 91.2% for sensitivity and 100% for specifity in this method. CONCLUSIONS The duplex Slidex~-staph monoclonal antibody examinated to SA and confirmed to MRSA has higher sensitivity and specificity.

Effect of morphine on serum hungry-induced apoptosis in cardiac myocytes / 中国药理学通报

Aim Myocardial cells of neonatal rats were cultured in vitro to study aim of morphine on serum hungry-induced apoptosis in cardiac myocytes and its mechanism.Methods Myocardial cells of neonatalrats were cultured in vitro.48 hours later,different agents were added to cardiac myocytes.The cellular survival was determined with MTT colormeteric assay;apoptosis rates were determined by Annexin V-FITC/PI;cell cycle was determined by flow cytometry;Caspase-3 and PKC were investigated by Western blot.Results Free-serum induced apoptosis in cardiac myocytes was shown after 48 hours;morphine(1 ?mol?L-1)could inhibit apoptosis in cardiac myocytes,manifestation,apoptosis rates were decreased,Caspase-3 experssion was decaeased Naloxone at 10 ?mol?L-1 inhibited the promoting effects of morphine;GF109203X at 10 ?mol?L-1 or Staurosporine at 1 ?mol?L-1 could inhibit the promoting effects of morphine,manifestation,apoptosis rates were increased,Caspase-3 experssion was incaeased,PKC expression was decreased.Conclusion morphine inhibited serum hungry-induced apoptosis in cardiac myocytes via PKC signal transduction pathway.

?-Opioid receptor inhibits serum deprivation-induced apoptosis of neonatal cardiac myocytes through activation of protein kinase C signal transduction pathway / 中国药理学通报

Aim To investigate the possible mechanism of ?-opioid receptor inhibiting serum deprivation-induced apoptosis of neonatal cardiac myocytes.Methods Myocardial cells of neonatal rats were cultured in vitro,after 48 h,the medium was changed to serum-free DMEM.The experimental groups were:A:Normal;B: Model;C: Model+DADLE(0.1 ?mol?L-1);D:Model+DADLE(0.1 ?mol?L-1)+naltrindole(10 ?mol?L-1);E:Model+DADLE(0.1 ?mol?L-1)+GF109203X(10 ?mol?L-1);F:Model+DADLE(0.1 ?mol?L-1)+staurosporine(1 ?mol?L-1).The cell viability was determined with MTT colormeteric assay;apoptosis index and the percentage of G0 in cell cycle were determined by flow cytometry;Caspase-3 and PKC signal pathway was investigated by Western blot.Results ?-opioid receptor agonist [D-Ala2,D-Leu5]-enkephalin(DADLE) could significantly inhibit serum deprivationinduced apoptosis of neonatal cardiac myocytes,which increased the survival index of cardiac myocyte,percentage of G2/M in cell cycle and the expression of PKC,decreased the apoptotic index of cardiac myocyte,percentage of G0/G1 in cell cycle and the expression of activate caspase-3.The protective effect of DADLE was obviously blocked by ?-opioid receptor antagonist Naltrindole at 10 ?mol?L-1,the PKC inhibitor GF109203X at 10 ?mol?L-1 and staurosporine at 1 ?mol?L-1,which decreased the survival index of cardiac myocyte,percentage of G2/M in cell cycle and the expression of PKC,increased the apoptotic index of cardiac myocyte,percentage of G0/G1 in cell cycle and the expression of caspase-3.Conclusion These findings suggested that ?-opioid receptor activation might be a potential survival factor against serum deprivation-induced myocardial cell apoptosis and this cardioprotective effect might be via PKC pathway.