Basic biological characteristics of lncRNA B230352I09 and its role in the process of myocardial injury / 中华急诊医学杂志

Objective:To explore the basic biological characteristics of lncRNA B230352I09 and its role in the process of myocardial injury.Methods:We analyzed the biological characteristics of lncRNA B230352I09 on the UCSC website and predicted the possible binding protein of lncRNA B230352I09 by the catRAPID. Real-time fluorescence quantitative (RT) PCR method was applied to detect the expression of lncRNA B230352I09 in heart tissues at different time points (0, 1, 3, 7d) within 7 days after birth, the organs distribution and expression of lncRNA B230352I09 in neonatal mouse and the expression pattern of lncRNA B230352I09 in the heart of mice with myocardial injury. In addition, we constructed hypoxia model by culturing primary cardiomyocytes to detect the effect of lncRNA 230352I09 overexpression on hypoxic cardiomyocyte apoptosis by Hoechst staining kit, the effect of lncRNA B230352I09 overexpression on ROS content of hypoxic cardiomyocyte by DCFDA probe and changes in mitochondrial membrane potential of hypoxic cardiomyocytes by JC-1 Fluorescent probes.Results:Full-length of mouse B230352I09 was 663bp, located in the chr7:123031415-123066439 forward strand. RBBP6 gene was adjacent to B230352I09, which may be the target of lncRNA B230352I09 by catrapid prediction analysis. With the development of the heart, the expression level of lncRNA B230352I09 showed a gradual downward trend. The main expression organs of lncRNA B230352I09 in 1-day-old mice were heart, brain, kidney and liver. In heart tissue, lncRNA B230352I09 expression in non-cardiomyocytes was significantly less than in cardiomyocytes [ (1.0± 0.03) vs. (9.2± 3.29), P=0.013]. After myocardial injury, the expression level of lncRNA B230352I09 showed an increasing trend compared with the normal developing mice, but there was no statistical significance. Hoechst staining showed that lncRNA B230352I09 could inhibit the apoptosis of hypoxic cardiomyocytes. Detecting the content of ROS in cardiomyocytes showed that compared with the hypoxia group, the generation of ROS was significantly reduced in the lncRNA B230352I09 overexpression group ([(3.8±0.71) vs. (1.65±0.56), P=0.015]). JC-1 fluorescent probe was used to detect the mitochondrial membrane potential, and the results showed that the mitochondrial membrane potential of cardiomyocytes in the lncRNA B230352I09 overexpression group was significantly higher than that in the hypoxia group. Conclusions:In heart tissue, lncRNA B230352I09 was mainly expressed in cardiomyocytes. LncRNA B230352I09 has a protective effect in the process of myocardial injury in mice, mainly by inhibiting apoptosis of cardiomyocytes, reducing ROS production, and protecting mitochondrial membrane potential of cardiomyocytes.

One-step synthesis of site-specific antibody-drug conjugates by reprograming IgG glycoengineering with LacNAc-based substrates

Glycosite-specific antibody‒drug conjugatess (gsADCs), harnessing Asn297 N-glycan of IgG Fc as the conjugation site for drug payloads, usually require multi-step glycoengineering with two or more enzymes, which limits the substrate diversification and complicates the preparation process. Herein, we report a series of novel disaccharide-based substrates, which reprogram the IgG glycoengineering to one-step synthesis of gsADCs, catalyzed by an endo-N-acetylglucosaminidase (ENGase) of Endo-S2. IgG glycoengineering via ENGases usually has two steps: deglycosylation by wild-type (WT) ENGases and transglycosylation by mutated ENGases. But in the current method, we have found that disaccharide LacNAc oxazoline can be efficiently assembled onto IgG by WT Endo-S2 without hydrolysis of the product, which enables the one-step glycoengineering directly from native antibodies. Further studies on substrate specificity revealed that this approach has excellent tolerance on various modification of 6-Gal motif of LacNAc. Within 1 h, one-step synthesis of gsADC was achieved using the LacNAc-toxin substrates including structures free of bioorthogonal groups. These gsADCs demonstrated good homogeneity, buffer stability, in vitro and in vivo anti-tumor activity. This work presents a novel strategy using LacNAc-based substrates to reprogram the multi-step IgG glycoengineering to a one-step manner for highly efficient synthesis of gsADCs.

Chalcones bearing N, O, and S-heterocycles: Recent notes on their biological significances

Because of its relatively easy synthesis, chalcone skeleton has been as a point of interest for organic and medicinalchemists from research groups worldwide. Chalcone scaffold constitutes the core of some interesting biologicallyactive natural products. Chalcone derivatives are among feasible potent active agents, such as anticancer, antibacterial,antifungal, antileishmanial, antimalarial, and antiviral. Due to the knowledge of heterocyclic chemistry, recentlychalcones bearing heterocyclic moieties have been synthesized and biologically investigated for specific target ofdiseases. The current review focuses on the latest application of chalcones integrated with N, O, and S-heterocyclicsystem and their wide spectrum of biological performance during 10 years (2010–2019). The results reported inthe review indicate that many chalcone-heterocycle hybrids may be useful as future drug candidates due to theircomparable or higher activity than that of the standards.

Potent gene screening strategy based on family-based patients with lumbar discherniation / 西安交通大学学报(医学版)

Objective: To look for a potent gene that may cause intervertebral disc degeneration in a family with intervertebral disc herniation by exome sequencing four patients with intervertebral disc herniation so as to provide possible help for studies on the causes and mechanisms of intervertebral disc diseases. Methods: We collected the serum of patients with lumbar disc herniation treated at The First Affiliated Hospital of Xi'an Jiaotong University, The First Affiliated Hospital of Xi'an Medical College, and Xi'an Tangcheng Hospital from January 2010 to December 2016. A detailed medical history was collected and family survey was conducted to find a family with high incidence of degenerative intervertebral disc disease. Then we found 4 patients aged 20 to 50 years with lumbar disc herniation in this family. Exome sequencing was used to analyze the common exon mutation sites of the 4 patients to find the common mutation sites. Results: The common mutation IGFBP6, Chr12:g.53494591T>C, was detected in the 4 samples. The Sanger sequencing performed in-family validation revealed that the IGFBP6 showed a C/T type in all the four patients and a T type in all the five normal controls. Finally, verification was performed in 200 normal controls and no mutation was found in this site. Therefore, the IGFBP6 might be the effector gene that caused intervertebral disc degeneration in this family. Conclusion: The mutation site of IGFBP6, c.T430C (p.S144P) (Chr12:g.53494591T>C), may be a factor that contributes to the high incidence of intervertebral disc herniation in this family. We still need to verify the function of the gene in future. Our study has also confirmed that exome sequencing technology can be applied to the detection of disease-causing genes in complex diseases.

A fatal case of Staphylococcal Scalded skin syndrome associated with Iatrogenic Cushing syndrome due to potent topical steroid application in a 3-month-old female: A case report

Introduction@#Cushing syndrome caused by application of topical corticosteroids is rarely reported. Systemic side effects like suppression of hypothalamic-pituitary-adrenal axis, growth retardation in children and iatrogenic Cushing syndrome can occur even in small doses of potent topical steroids.1@*Case Summary@#This is a case of a 3-month old female who was referred to our department due to generalized erythema with desquamation. History revealed that the patient had recurrent eczema and the mother applied an over-the-counter medication containing Ketoconazole+Clobetasol 10mg/500mcg per 7-gram cream thrice daily for ten weeks. The estimated topical steroid applied weekly was around 8.5 grams and at time of admission, the patient had been exposed to approximately 50 grams of a potent topical corticosteroid. The patient presented with fever, irritability, and had positive Nikolsky sign thus managed as a case of staphylococcal scalded skin syndrome associated with topical steroid – induced iatrogenic Cushing syndrome. Unfortunately, patient’s condition worsened and with progressive pneumonia, she expired on the 23rd hospital day. The fatal outcome was due to SSSS which was complicated by progressive pneumonia and topical steroid – induced iatrogenic Cushing syndrome. The complex interplay of these features eventually led to sepsis and death.@*Conclusion@#This case highlights the risks related to abuse of potent steroid-containing preparations and the importance of education to prevent severe and catastrophic outcomes of injudicious steroid use.

Comparison between topical tacrolimus and potent topical steroids in treatment of childhood vitiligo / 重庆医学

Objective To assess which of topical tacrolimus and topical highly potent steroids,is more effective and safer in the treatment of pediatric vitiligo.Methods The PubMed,Cochrane library,Scopus and CINAHL plus databases were retrieved.The search was confined to English language articles.The randomized controlled trial(RCT) articles were included in our study.The quality of the identified articles was examined by using the CASP Randomised Controlled Trials Checklist.Results As a result,there were only a few studies related to the comparison.However,there were only two RCTs regarding a comparison of topical tacrolimus 0.1％ and clobetasol propionate 0.05 ％ in childhood vitiligo.Conclusion When the body surface area (BSA) involved in the child is ＜20 ％,and the disease is not rapidly spreading,topical therapy is the first choice.Topical tacrolimus may be considered as an alternative therapy for childhood vitiligo,especially for acrofacial and segmental types,before considering other modalities,but still need to observe long-term side effects.

Synovial Sarcoma Vulva: A Case Report.

Introduction: Contrary to its name, synovial sarcoma does not arise from the synovial membrane but from multi-potent stem cells and can present in any part of the body. Very few cases of vulval synovial sarcoma have been reported in the literature; we report on such a presentation. Th ese tumors can present as painless lumps, which must be completely excised to give the best prognosis. Th erefore the diagnosis of synovial sarcoma should always be kept in mind in the management of vulval masses, especially in young patients.

Influence on Serum Inflammatory Factors Level and Efficacy of Octreotide Combined with Potent Purga-tive Decoction with Additions in Patients with Early Postoperative Inflammatory Bowel Obstruction ( EPIS-BO) after Abdominal Operation / 中国药师

Objective:To discuss the influence and curative effect of octreotide combined with potent purgative decoction with ad-ditions on serum inflammatory factors level in the patients with early postoperative inflammatory bowel obstruction ( EPISBO) after ab-dominal operation. Methods: Totally 78 cases of patients with EPISBO after abdominal operation were divided into the observation group and the control group with 39 ones in each. The patients in the two groups were given the basic medical treatment, such as fast-ing, water deprivation, gastrointestinal decompression, maintenance of water, electrolyte and acid-base balance, infection prevention, parenteral nutrition support and etc. The patients in the control group were given 0. 1mg octreotide via hypodermic injection, q8h, while the patients in the observation group were additionally given potent purgative decoction with additions, one dose per day comple-ted by twice or three times through mouth or nasogastric tube. The course of treatment was 1 week. The changes of serum hs-CRP and TNF-α levels in the two groups before the treatment and after the medical treatment were observed and compared, and the curative effect and adverse drug reactions ( ADR) were evaluated as well. Results: After the one-week medical treatment, the serum hs-CRP and TNF-α levels in the two groups were obviously declined (P0. 05). Conclusion:Octreotide combined with potent purgative decoction with additions has significant curative effect in the patients with EPISBO after abdominal operation with high security, and the mechanisms are related with such effects as reducing serum hs-CRP and TNF-α levels and inhibiting local inflammatory response in intestinal tract.

Topical corticosteroid abuse on the face: A prospective, multicenter study of dermatology outpatients .

Background: Abuse of topical corticosteroids (TC), especially over the face, is prevalent worldwide, including in India. Data about the magnitude of this problem in our country is lacking. Aims: The aims of this study were to ascertain the demographics, magnitude and clinical features of TC misuse on the face in the dermatology outpatient department (OPD) attendees in order to raise awareness about this problem and to analyze its causes. Methods: This was a prospective multicenter questionnaire-based clinical study conducted at 12 dermatology centers nationwide. Patients with relevant facial dermatoses reporting to the investigator were asked about their current use of over-the-counter topical formulations and a structured questionnaire applied in case the same was confirmed to be TC. Results: A total of 2926 patients with facial dermatoses were screened, of which 433 (14.8%) were using TC. TC was used as a fairness/general purpose cream or aftershave in 126 (29%) and in 104 (24%) for acne. Steroid combinations were used by 258 (59.6%). Potent and super-potent TC were significantly (P = 0.05) more frequently used by the rural/suburban population. The younger age groups used more potent formulations. A non-physician recommendation for TC use was obtainable in 257 (59.3%) patients. Of these, 232 (90.3%) were for potent/super-potent steroids. Among 176 physician prescriptions, 78 (44.3%) were from non-dermatologists. All non-physician prescriptions and 146 (83%) physician prescriptions for TC were inappropriately refilled. Adverse effects were seen in 392 (90.5%) TC users. Acne/exacerbation of acne was the most common adverse effect. Conclusions: TC misuse in patients with facial dermatoses is quite common, and most of this use is unwarranted. Use as a fairness cream is the most common indication in this cohort. Limitations: This was an OPD-based study and, therefore, it may or may not accurately reflect the community data.

Analysis and determination of diterpenoids in unprocessed and processed Euphorbia lathyris seeds by HPLC-ESI-MS / 药物分析学报

Euphorbia lathyris (Caper spurge) is a toxic and potent Chinese materia medica (T/PCMM).This study sought a method for identifying five diterpenoids (Euphorbia factors L1-L3,L7a and L8) with the spectra of UV and mass,quantifying three diterpenoids L1,L2,and L8 in crude extracts of unprocessed and processed E.lathyris seeds by liquid chromatography/electrospray ionization mass spectrometry (LC-ESI-MS).The analysis was achieved on an Agilent Eclipse XDB-C18 column (4.6 mm × 150 mm i.d.,5 μm) with an isocratic elution with a mobile phase consisting of water and acetonitrile at a flow rate of 0.25 mL/min at column temperature of 30 ℃ and UV detection was set at 272 nm.An ESI source was used with a positive ionization mode.The calibration curve was linear in the ranges of 9.9-79 μg/mL for Euphorbia factor L1,3.8-30.5 μg/mL for Euphorbia factor L2,and 1.0-20.6 μg/mL for Euphorbia factor L8.The average recoveries (n=6) of three diterpenoids were 98.39％,91.10％ and 96.94％,respectively,with RSD of 2.5％,2.4％ and 2.1％,respectively.The contents of the three diterpenoids in processed E.lathyris seeds were 3.435,1.367 and 0.286 mg/g,respectively,which decreased more sharply than those in unprocessed E.lathyris seeds which were 4.915,1.944 and 0.425 mg/g,respectively.The method is simple,accurate,reliable and reproducible,and it can be applied to control the quality of unprocessed and processed E.lathyris seeds.

HPV type 18 is more oncopotent than HPV16 in uterine cervical carcinogenesis although HPV16 is the prevalent type in Chennai, India.

Context: The highest incidence of uterine cervical cancer in India is reported in Chennai. The prevalence and oncopotency are to be considered for the development of vaccines and therapeutic agents. Aims: The aim of the present study is to analyze the prevalence and oncopotency of high risk type HPV16 and 18 in cervical lesions. Settings and Design: This study is designed with 130 study subjects for analysis of selected types of HPV 6/11 and 16/18, in four groups, in a course of three years. The Bethesda system of classification is followed for grouping the samples, using histopathologic examination in biopsies. Materials and Methods: The biopsy samples were collected in 10% buffered formalin and were embedded in paraffin within 24 hours, for long-term preservation. The presence of HPV types were tested by PCR using type-specific primers for HPV16 and HPV18 in the DNA isolated from the subject's biopsies. The stages of cervical lesions were identified by histopathology using the Hematoxylin Eosin stain. Statistical Analysis Used: The data were subjected to statistical analysis, using the SPSS and INSTAT software packages for their associations and risk estimation, respectively. The Graph Pad Prism 2 x 2 contingency table was used for risk estimation and the Kruskel Wallis test was used for analysis of the associations. Results: In the study population, the data indicated a high prevalence of HPV 16. However, during the course of study (1999 - 2003), four (66.6%) dysplasia cases with HPV 18, three (21.4%) dysplasia cases with HPV 16, and none with low-risk HPV6/11, turned into invasive cancer, within one year. Conclusions: The observation of the study implied that HPV16 had a high prevalence in uterine cervical cancer compared with HPV18 cases. However, the development of invasive cancer from precancerous lesions was more for HPV18 infected cases than for HPV16 during the study period, which indicated the higher oncopotency of HPV type 18.

CKbeta8-1 alters expression of cyclin E in colony forming units-granulocyte macrophage (CFU-GM) lineage from human cord blood CD34 + cells

A C6 beta-chemokine, CKbeta8-1, suppressed the colony formation of CD34 + cells of human cord blood (CB). Molecular mechanisms involved in CKbeta8-1-medicated suppression of colony formation of CD34 + cells are not known. To address this issue, the level of various G1/S cell cycle regulating proteins in CKbeta8-1-treated CD34 + cells were compared with those in untreated CD34 + cells. CKbeta8-1 did not significantly alter the expression of the G1/S cycle regulation proteins (cyclin D1, D3, and E), CDK inhibitor (p27and Rb), and other cell proliferation regulation protein (p53) in CB CD34 + cells. Here we describe an in vitro system in which CB CD34 + cells were committed to a multipotent progenitor lineage of colony forming units-granulocyte/macrophage (CFU-GM) by a simple combination of recombinant human (rh) GM-CSF and rhIL-3. In this culture system, we found that cyclin E protein appeared later and disappeared faster in the CKbeta8-1-treated cells than in the control cells during CFU-GM lineage development. These findings suggested that cyclin E may play a role in suppressing the colony formation of CFU-GM by CKbeta8-1.