Adherence to human small intestines of capsulated Vibrio cholerae O139

Abstract Capsulated cells of V. cholerae O139 adhered to formalis-fixed or native mucosa of the small intestines from an adult and a child. The primary adherence target was mucus. Capsulated O139 cells adhered better to the antigen sampling cells (M cells) of ileal Peyer's patch than to the absorptive cells. O139 cells on the mucosa appeared as small aggregates. Similar organisms were found on the mucosa of duodenal biopsy samples from patients infected with V. cholerae O139. The findings indicated that capsulated cells of V. cholerae O139 tend to autoagglutinate and contribute to the effective adherence to the intestinal mucosa.     

Induction of opsonic antibodies to the gamma-D-glutamic acid capsule of Bacillus anthracis by immunization with a synthetic peptide-carrier protein conjugate

The capsule of Bacillus anthracis, a polymer of gamma-D-glutamic acid, functions as a virulence determinant and is a poor immunogen. In this study we show that antibodies reactive with the B. anthracis capsule can be elicited in mice by immunization with a conjugate consisting of a synthetic gamma-D-glutamic acid nonamer peptide (gamma-D-glu9) covalently coupled to keyhole limpet hemocyanin. The serum response to gamma-D-glu9 was comprised primarily of IgG antibodies that recognized an epitope requiring a minimum of four gamma-linked D-glutamic acid residues. Antibodies to (gamma-D-glu9) bound to the surface of encapsulated B. anthracis cells and mediated opsonophagoctosis. These findings suggest that anti-capsular antibodies could mediate the clearance of vegetative B. anthracis cells in vivo. Thus, inclusion of an immunogenic capsular component as well as protective antigen in new anthrax vaccines would generate immune responses targeting both the bacteremic and toxigenic aspects of anthrax infection and thus may increase protective efficacy.     

电针腧穴联合当飞利肝宁治疗非酒精性脂肪性肝炎的临床研究

目的:探讨电针腧穴联合当飞利肝宁治疗非酒精性脂肪性肝炎(nonalcohlic steatohepatitis,NASH)的临床疗效及其安全性。方法:选择符合2010年非酒精性脂肪性肝病诊疗指南[1]诊断标准的80例非酒精性脂肪性肝炎患者,随机分为联合组(电针联合当飞利肝宁治疗组)和对照组(护肝宁治疗组)各40例,两组患者均在纠正不良生活方式、控制饮食(BMI24)、适量有氧运动等的基础上给予相应的治疗,对照组仅服用护肝宁,3次/d,联合组服用当飞利肝宁及电针腧穴治疗。观察和比较两组的疗效、血清转氨酶、血脂水平、脂肪肝程度变化和不良反应的发生情况。结果:联合组和对照组的治疗总有效率分别为90.0%和62.5%,两组总有效率比较有显著性差异(P0.05)。治疗后,联合组患者的血清转氨酶、血脂水平均较对照组显著降低(P0.05)。治疗中两组均未发现明显不良反应。结论:电针腧穴联合当飞利肝宁对非酒精性脂肪性肝炎有较好的治疗效果,具有很高的临床应用价值。     

Shufeng Jiedu,a promising herbal therapy for moderate COVID-19:Antiviral and anti-inflammatory properties,pathways of bioactive compounds,and a clinical real-world pragmatic study

BackgroundShufeng Jiedu capsules (SFJDC), a patented herbal drug composed of eight medicinal plants, is used for the treatment of different viral respiratory tract infectious diseases. Based on its antiviral, anti-inflammatory and immunoregulatory activity in acute lung injury, SFJDC might be a promising candidate for the treatment of COVID-19.PurposeTo evaluate the antiviral and anti-inflammatory properties and to discover the mechanism of action of SFJDC as a potential drug for the treatment of COVID-19. Furthermore, the study should determine the clinical effectiveness of SFJDC for the treatment of COVID-19.DesignWe analyzed the antiviral and anti-inflammatory effects of SFJDC in a HCoV-229E mouse model on lung index, virus load in the lung, the release of cytokines, and on T- and B-lymphocytes. The mechanism of action was further investigated by network analysis. Additionally, we investigated data from a clinical pragmatic real-world study for patients with confirmed COVID-19, to evaluate the clinical effect of SFJDC and to determine the best time to start the treatment.ResultsSFJDC significantly reduced the virus load in the lung of HCoV-229E mice (from 1109.29 ± 696.75 to 0 ± 0 copies/ml), decreased inflammatory factors IL-6, IL-10, TNF-α, and IFN-γ in the lung, and increased the amount of CD4⁺ and CD8⁺ cells in the blood compared to the model group. Network analysis revealed that SFJDC reduces the activity of NFκB via several signaling pathways. Quercetin, wogonin, and polydatin bind directly to the main protease (M^pro) of SARS-CoV-2.Clinical data showed that SFJDC, added to standard antiviral therapy (AVD), significantly reduced the clinical recovery time of COVID-19 and fatigue (from 3.55 ± 4.09 to 1.19 ± 2.28 days) as well as cough (from 5.67 ± 5.64 to 3.47 ± 3.75) days compared to AVD alone. SFJDC therapy was significantly more effective when used within the first 8 days after the onset of symptoms.ConclusionSFJDC might be a promising drug for the treatment of COVID-19, but large-scale randomized, double-blinded, placebo-controlled clinical trials are needed to complement the real-world evidence. It might be beneficial to start SFJDC treatment as early as possible in suspected cases of COVID-19.     

细菌“特殊结构”之浅见

细菌的结构是病原生物学课程教学中最为基础的教学内容.随着科学技术和研究方法的发展,人们对细菌结构的认识也愈加深入.对国内教材普遍采用的细菌“特殊结构”概念提出不同的观点,试与同行切磋探讨.     

Dissection of Hexosyl- and Sialyltransferase Domains in the Bifunctional Capsule Polymerases from Neisseria meningitidis W and Y Defines a New Sialyltransferase Family

Crucial virulence determinants of disease causing Neisseria meningitidis species are their extracellular polysaccharide capsules. In the serogroups W and Y, these are heteropolymers of the repeating units (→6)-α-d-Gal-(1→4)-α-Neu5Ac-(2→)_n in NmW and (→6)-α-d-Glc-(1→4)-α-Neu5Ac-(2→)_n in NmY. The capsule polymerases, SiaD_W and SiaD_Y, which synthesize these highly unusual polymers, are composed of two predicted GT-B fold domains separated by a large stretch of amino acids (aa 399–762). We recently showed that residues critical to the hexosyl- and sialyltransferase activity are found in the predicted N-terminal (aa 1–398) and C-terminal (aa 763–1037) GT-B fold domains, respectively. Here we use a mutational approach and synthetic fluorescent substrates to define the boundaries of the hexosyl- and sialyltransferase domains. Our results reveal that the active sialyltransferase domain extends well beyond the predicted C-terminal GT-B domain and defines a new glycosyltransferase family, GT97, in CAZy (Carbohydrate-Active enZYmes Database).     

扶正化瘀胶囊对鼠血吸虫肝纤维化的作用及机制探讨

目的:研究扶正化瘀胶囊对实验性血吸虫病肝纤维化的影响,探讨其相关作用机制。方法:70只昆明小鼠分为正常对照组(A)、模型组(B)、吡喹酮组(C)、INF-γ组(D)、扶正化瘀胶囊低剂量组(E)、中剂量组(F)、高剂量组(G),采用日本血吸虫尾蚴30条/只攻击感染小鼠建立血吸虫性肝纤维化模型。第6周用吡喹酮驱虫治疗后予扶正化瘀胶囊干预,第14周末观察血清透明质酸、层粘连蛋白、III型前胶原、IV型胶原水平,HE染色观察肝脏病理改变及虫卵结节变化,免疫组化检测PDGF-BB和I、III型胶原的表达。结果:扶正化瘀胶囊各剂量组肝脏病理损伤减轻,虫卵肉芽肿面积和数量明显减小;血清HA、LN、PC-III、C-IV水平显著下降(P<0.05);肝组织I、III型胶原和PDGF-BB表达明显低于模型组(P<0.05)。结论:扶正化瘀胶囊具有抗血吸虫性肝纤维化作用,降低肝组织PDGF-BB的表达可能是其抗纤维化作用机制之一。     

Impaired capsule formation of tumors in periostin-null mice

Being a secreted protein, periostin is a multifunctional matricellular glycoprotein. In vitro, periostin has the ability to promote the proliferation and migration of fibroblasts. Previously, it was demonstrated that periostin is mainly produced by cancer-associated fibroblasts or tumor stromal cells. In the present study, we show that periostin regulates capsule formation in a positive manner and inhibits tumor growth. Consistent with a previous finding, several tumor cell lines did not exhibit expression of periostin in vitro or in vivo; and the growth of tumors that had been allografted into periostin −/− mice was significantly accelerated compared with that of the same kind of tumors grafted into periostin +/+ mice. Immunostaining and biochemical analyses revealed that mature collagen was detected abundantly in the capsules and interstitium of the wild-type-grafted tumors but not in those of the periostin −/− grafted tumors. Moreover, the number of activated tumor stromal cells was decreased significantly in the periostin −/− grafted tumors. Our studies suggest that host-derived periostin negatively regulates tumor growth by promoting capsule formation and by mediating changes in the deposition and organization of the tumor microenvironment coordinated by periostin-producing stromal cells.     

复方银杏胶囊镇痛作用及其机制的实验研究

目的:研究复方银杏胶囊的镇痛作用及其机制.方法:大鼠电刺激法测定痛阈;用试剂盒比色法测定脑组织中谷氨酸的含量;原子吸收光谱法测定脑组织中钙离子(Ca2 )浓度;免疫组织化学ABC法观察脑组织中N-甲基-D-天门冬氨酸Ⅰ型受体(NMDAR1)的分布.结果:复方银杏胶囊350 mg/kg可显著提高大鼠电刺激嘶叫阈(P＜0.05),700 mg/kg显著减少小鼠脑组织中谷氨酸的释放以及脑内钙离子浓度(P＜0.05);复方银杏胶囊700 mg/kg、350 mg/kg可明显减少疼痛模型小鼠大脑皮层NMDAR1阳性细胞数(P＜0.01,P＜0.05).结论:复方银杏胶囊具有良好的镇痛效应,其镇痛作用可能与拮抗NMDA受体从而抑制脑组织中谷氨酸的释放及钙离子内流有关.     

科博肽肠溶胶囊治疗晚期中、重度癌症疼痛疗效观察

目的 探讨科博肽肠溶胶囊对晚期癌症患者的止痛效果。方法 每6h口服科博肽肠溶胶囊280μg/次,常规剂量每天560μg,在用药过程中根据疼痛缓解程度调整剂量由280μg～420μg～560μg递增。结果 68例中、重度癌痛患者,显效41例,有效21例,无效6例,总有效率91．2％,药物最小日剂量280μg,最大日剂量为840μg,所有患者均可耐受,未见有药物依赖性。结论 科博肽肠溶胶囊作为控制中、重度癌痛的药物,其镇痛效果满意,副反应少,服用方便,安全,值得临床推广应用。