Antibacterial, Anti-Inflammatory and Antioxidant Activities of an ACAZY Herbal Formula Used in Traditional Medicine to Treat Respiratory Infections

ACAZY is a plant formula used in traditional medicine in Burkina Faso to treat respiratory infections. After phytochemical analysis, this study evaluated extracts’ anti-inflammatory, antioxidant and antibacterial properties from the ACAZY recipe. Three extractions, an aqueous macerate (AM), an aqueous decoction (AD) and an hydroethanolic macerate (HEM) of the ACAZY recipe powder were carried out. Phytochemical screening of the extracts was carried out using high-performance thin-layer chromatography (HPTLC) and the determination of phenolic compounds. The anti-inflammatory potential was assessed in vitro using pro-inflammatory enzyme inhibition tests. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and Ferric-reducing antioxidant power (FRAP) antioxidant properties were also determined. The antibacterial activity was evaluated on Staphylococcus aureus and Streptococcus pneumoniae strains. Phytochemical analysis revealed the presence of flavonoids, saponins, tannins, anthracenosids, sterols and triterpenes in the extracts. The extracts inhibited pro-inflammatory enzymes by more than 40% at only 100 µg/mL. The extracts also showed potent antibacterial activity with a minimum inhibitory concentration 1 mg/mL on Staphylococcus aureus and 2 mg/mL on Streptococcus pneumoniae. The extracts in the ACAZY formula have shown anti-inflammatory and antioxidant properties in vitro. The AD also showed an antibacterial activity. This justifies its use in traditional medicine to treat acute respiratory infections.

Implications for Antigravity Tests of Dirac’s Negative Energy Antiparticles

P. A. M. Dirac conceived antimatter in 1928 as having negative energy by allowing a consistent representation of matter-antimatter annihilation into light. To achieve compatibility with special relativity, particle physics of the early 20th century made the theoretical assumption that antiparticles have positive energy, an assumption that remains in effect as of today. In this note we prove apparently for the first time a theorem stating that positive mass antiparticles violate Dirac’s particle-antiparticle annihilation into light. We then show the consequential unsettled character of the recent gravity test of the anti-Hydrogen atom due to the positive mass of its nucleus. We conclude by suggesting that a final scientific claim on matter-antimatter gravity requires tests on particles with clear antimatter character, such as the 1994 resolutory proposal for the comparative test of the gravity of very low energy electron and positron in horizontal flight on a supercooled vacuum tube.

类风湿关节炎合并骨关节炎病人血清anti-Sa、anti-CCP水平与骨关节损伤、全身炎症反应的相关性分析

目的:分析类风湿关节炎(RA)病人血清anti-Sa、anti-CCP抗体水平与其骨关节损伤、全身炎症反应的相关性。方法:选择RA合并骨关节损伤病人108例,根据血清anti-Sa、anti-CCP抗体水平分别列入高anti-Sa组和低anti-Sa组、高anti-CCP组和低anti-CCP组。比较各组病人WOMAC骨性关节炎指数、lysholms膝关节功能评分值,血清白细胞介素(IL)-1β、IL-6、IL-27、肿瘤坏死因子α(TNF-α)水平。采用Pearson检验评估有关指标的相关性。结果:高anti-Sa组、高anti-CCP组病人的WOMAC骨性关节炎指数明显高于低anti-Sa组(P<0.01),lysholms膝关节功能评分明显低于低anti-Sa组(P<0.01);血清中IL-1β、IL-6、IL-27、TNF-α的水平明显高于低anti-CCP组(P<0.01)。RA病人血清anti-Sa、anti-CCP抗体水平与骨关节损伤、全身炎症反应严重程度呈正相关关系(P<0.05~P<0.01),与lysholms膝关节功能评分呈负相关关系(P<0.01)。结论:RA病人血清中anti-Sa、anti-CCP抗体水平显著升高与关节损伤及全身炎症反应有一定的相关性,可作为临床判断病情活动性与骨关节损伤的参考指标。

Primary biliary cirrhosis:What do autoantibodies tell us?

Primary biliary cirrhosis(PBC) is a chronic,progressive,cholestatic,organ-specific autoimmune disease of unknown etiology.It predominantly affects middle-aged women,and is characterized by autoimmune-mediated destruction of small-and medium-size intrahepatic bile ducts,portal inflammation and progressive scarring,which without proper treatment can ultimately lead to fibrosis and hepatic failure.Serum autoantibodies are crucial tools for differential diagnosis of PBC.While it is currently accepted that antimitochondrial antibodies are the most important serological markers of PBC,during the last five decades more than sixty autoantibodies have been explored in these patients,some of which had previously been thought to be specific for other autoimmune diseases.

类风湿性关节炎滑膜病变高频超声表现与Anti-ccp、ESR及CRP的相关性

目的分析类风湿性关节炎(RA)滑膜病变高频超声表现与抗环瓜氨酸肽抗体(Anti-CCP)、红细胞沉降率(ESR)和C反应蛋白(CRP)的相关性,以期为该疾病早期诊断及治疗方案的制定提供更为准确和科学的依据。方法选取2020年1月至2023年3月于大庆龙南医院风湿免疫科住院的治疗前RA患者65例(RA组),另选取同期于本院体检中心行体检的健康者55名(对照组)。比较两组高频超声表现、髌上囊液体厚度、滑膜厚度、滑膜动脉RI及实验室指标(Anti-ccp、ESR及CRP水平),RA组根据Anti-ccp、ESR及CRP阳性标准分为阳性、阴性组,比较Anti-ccp、ESR及CRP阳性及阴性组的髌上囊液体厚度、滑膜厚度、滑膜动脉RI。采用Pearson分析滑膜病变高频超声表现各指标与Anti-ccp、ESR及CRP的相关性。结果对照组膝积液少<4 mm;RA组80%膝积液>4 mm,多对称,尤见于内外侧隐窝。对照组滑膜难辨,RA组滑膜增厚、低回声、分界清、表面糙、见绒毛。彩超示RA组81.53%膝滑膜有明显血流信号,多为Ⅱ、Ⅲ级。RA组髌上囊液体厚度、滑膜厚度、Anti-ccp、ESR及CRP水平均高于对照组,滑膜动脉RI则低于对照组,差异有统计学意义(P<0.05);Anti-ccp、ESR及CRP阳性组髌上囊液体厚度、滑膜厚度水平均显著高于阴性组,滑膜动脉RI低于阴性组,差异有统计学意义(P<0.05)。髌上囊液体厚度、滑膜厚度与Anti-ccp、ESR及CRP水平均呈正相关(P<0.05);滑膜动脉RI与Anti-ccp、ESR及CRP水平均呈负相关(P<0.05)。结论高频超声可清晰观察RA患者的滑膜病变情况,且与Anti-ccp、ESR及CRP等实验室指标存在显著关联性,可为临床诊断RA滑膜病变患者提供有力的参考依据,利于制定更具针对性的治疗措施。

Impact of preformed donor-specific antibodies against HLA class Ⅰ on kidney graft outcomes:Comparative analysis of exclusively anti-Cw vs anti-A and/or-B antibodies

AIM To analyze the clinical impact of preformed antiH LA-Cw vs antiH LA-A and/or-B donor-specific antibodies(DSA) in kidney transplantation.METHODS Retrospective study, comparing 12 patients transplanted with DSA exclusively antiH LA-Cw with 23 patients with preformed DSA antiH LA-A and/or B.RESULTS One year after transplantation there were no differencesin terms of acute rejection between the two groups(3 and 6 cases, respectively in the DSA-Cw and the DSA-A-B groups; P = 1). At one year, eG FR was not significantly different between groups(median 59 mL /min in DSA-Cw group, compared to median 51 mL /min in DSA-A-B group, P = 0.192). Moreover, kidney graft survival was similar between groups at 5-years(100% in DSA-Cw group vs 91% in DSA-A-B group, P = 0.528). The sole independent predictor of antibody mediated rejection(AMR) incidence was DSA strength(HR = 1.07 per 1000 increase in MFI, P = 0.034). AMR was associated with shortened graft survival at 5-years, with 75% and 100% grafts surviving in patients with or without AMR, respectively(Log-rank P = 0.005).CONCLUSION Our data indicate that DSA-Cw are associated with an identical risk of AMR and impact on graft function in comparison with "classical" class I DSA.

Peri-nuclear antibodies correlate with survival in Greek primary biliary cirrhosis patients

AIM:To investigate possible associations of anti-nuclear envelope antibody(ANEA)with disease severity and survival in Greek primary biliary cirrhosis(PBC)patients.METHODS:Serum samples were collected at diagnosis from 147 PBC patients(85%female),who were followed-up for a median 89.5 mo(range 1-240).ANEA were detected with indirect immunofluorescence on 1% formaldehyde fixed Hep2 cells,and anti-gp210 antibodies were detected using an enzyme linked immunosorbent assay.Findings were correlated with clinical data,histology,and survival.RESULTS:ANEA were detected in 69/147(46.9%) patients and 31/147(21%)were also anti-gp210 positive.The ANEA positive patients were at a more advanced histological stage(Ⅰ-Ⅱ/Ⅲ-Ⅳ56.5%/43.5% vs 74.4%/25.6%,P=0.005)compared to the ANEA negative ones.They had a higher antimitochondrial antibodies(AMA)titer(≤1:160/>1:160 50.7%/49.3%vs 71.8%/28.2%,P=0.001)and a lower survival time(91.7 ±50.7 mo vs 101.8±55 mo,P=0.043).Moreover,they had more advanced fibrosis,portal inflammation,interface hepatitis,and proliferation of bile ductules(P =0.008,P=0.008,P=0.019,and P=0.027,respectively).They also died more frequently of hepatic failure and/or hepatocellular carcinoma(P=0.016).ANEA positive,anti-gp210 positive patients had a difference in stage(Ⅰ-Ⅱ/Ⅲ-Ⅳ54.8%/45.2%vs 74.4%/25.6%,P= 0.006),AMA titer(≤1:160/>1:160 51.6%/48.4%vs 71.8%/28.2%,P=0.009),survival(91.1±52.9 mo vs 101.8±55 mo,P=0.009),and Mayo risk score(5.5 ±1.9 vs 5.04±1.3,P=0.04)compared to the ANEA negative patients.ANEA positive,anti-gp210 negative patients had a difference in AMA titer(≤1:160/>1:160 50%/50%vs 71.8%/28.2%,P=0.002),stage(Ⅰ-Ⅱ/Ⅲ -Ⅳ57.9%/42.1%vs 74.4%/25.6%,P=0.033),fibrosis(P=0.009),portal inflammation(P=0.018),interface hepatitis(P=0.032),and proliferation of bile ductules(P=0.031).Anti-gp210 positive patients had a worse Mayo risk score(5.5±1.9 vs 4.9±1.7,P=0.038)than the anti-gp210 negative ones.CONCLUSION:The presence of ANEA and anti-gp210 identifies a subgroup of PBC patients with advanced disease severity and poor prognosis.

Prevalence, significance and predictive value of antiphospholipid antibodies in Crohn's disease

AIM: To assess the prevalence and stability of different antiphospholipid antibodies(APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases(IBD) patients.METHODS: About 458 consecutive patients [Crohn's disease(CD): 271 and ulcerative colitis(UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course(development f complicated disease phenotype and need for surgery),occurrence of thrombotic events, actual state of diseaseactivity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up,(median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls(HC) were tested on individual anti-β2-Glycoprotein-I(anti-β2-GPI IgA/M/G), anti-cardiolipin(ACA IgA/M/G)and anti-phosphatidylserine/prothrombin(anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies(ASCA IgA/G) by enzyme-linked immunosorbent assay(ELISA). In a subgroup of CD(n = 198) and UC patients(n = 103), obtaining consecutive samples over various arbitrary timepoints during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally,we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed.RESULTS: Patients with CD had significantly higher prevalence of both ACA(23.4%) and anti-PS/PT(20.4%) antibodies than UC(4.8%, p < 0.0001 and10.2%, p = 0.004) and HC(2.9%, p < 0.0001 and15.5%, p = NS). No difference was found for the prevalence of anti-β2-GPI between different groups(7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients.Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes.Changes in antibody status were more remarkable in CD than UC(ACA IgA: 49.9% vs 23.3% and ACA IgG:21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis.CONCLUSION: The present study demonstrated enhanced formation of APLAs in CD patients. However,presence of different APLAs were not associated with the clinical phenotype or disease course.

Diagnostic Value of Antibodies against a Modified Citrullinated Vimentin in Rheumatoid Arthritis

Aim of Work: To investigate the value of the detection of antibodies against modified citrullinated vimentin antibodies (anti-MCV) in comparison with anti-CCP2-for the diagnosis of rheumatoid arthritis (RA). Patients and Methods: The study Included Forty patients with Rheumatoid arthritis (RA). They under went assessment by the disease activity score (DAS-28), visual analogue scale (VAS) and health assessment questionnaire (HAQ). Thirty healthy subjects matched for age and sex served as a control group. Blood samples were obtained from patients and controls for erythrocyte sedimentation rate (ESR), C reactive protein (CRP), rheumatoid factor (RF). Anti-CCP2 and anti-MCV were determined using ELISA technique. Results: Estimated serum levels of anti-CCP2 and anti-MCV were significantly higher in patients compared to controls (p 0.001). There were no significant correlations between anti-MCV levels and age, dis- ease duration, duration of morning stiffness, number of swollen and tender joints, HAQ or ESR in patients with RA, while serum levels correlates significantly with DAS28, VAS and CRP (p 0.05). Anti-CCP2 correlates significantly with DAS28, VAS and CRP and ANA (p 0.05). Serum anti-MCV and anti-CCP2 were significantly correlated with each other (r = 0.483;p The receiver operating characteristic (ROC) curve was drawn and it showed that anti-MCV had diagnostic specificity, sensitivity of 93.3%, 75.5%, respectively, while anti-CCP2 specificity, sensitivity of 98.1%, 85%, respectively. Conclusion: Serum anti-MCV as well as the anti-CCP-2 assay perform comparably well in the diagnosis of RA. In the high-specificity range, however, the anti-CCP2 assay appears to be superior to the anti-MCV test.

Anti-GM1影响裸鼠NK细胞分化和杀伤活性研究

目的研究抗单唾液酸神经节苷脂抗体(Anti-GM1)通过调节自然杀伤(NK)细胞分化,抑制裸鼠NK细胞的自然杀伤活性。方法多重免疫荧光染色鉴定人肾癌组织中NK细胞的分型特点。选择雄性BALB/c小鼠6只,GM1皮下注射每周1次,一共三周,以此来免疫小鼠制备Anti-GM1。选取6只BALB/c-Nude裸鼠,采用随机数字表法将裸鼠分为对照组(CON组)及实验组(Anti-GM1组),CON组用IgG连续腹腔注射7 d;Anti-GM1组用Anti-GM1连续腹腔注射7 d。7 d后经颈椎脱臼法处死裸鼠,取裸鼠脾脏并制成单细胞悬液,将脾细胞与YAC-1细胞共培养4 h。用LDH法检测NK细胞的杀伤活力。使用流式细胞术进行检测,根据CD27和CD11b表达来界定NK细胞亚群,同时检测CD107a的表达情况。ELISA检测NK细胞的γ干扰素(IFN-γ)及颗粒酶B(GzmB)分泌水平。结果人肾癌组织标本中有明显的NK细胞浸润现象,并且GzmB也呈现阳性表达。Anti-GM1可以显著抑制NK细胞的杀伤活力。与CON组相比,Anti-GM1组可以促进NK细胞向成熟亚群进行分化。Anti-GM1组NK细胞的CD107a水平显著下降。Anti-GM1组NK细胞的IFN-γ及GzmB分泌水平较CON组下降。结论NK细胞可以浸润在人肾癌组织中,并且能够分泌GzmB,发生自然杀伤作用。Anti-GM1可以促进NK细胞的成熟,但抑制NK细胞的杀伤活力,与其抑制NK细胞CD107a表达和抑制NK细胞的IFN-γ及GzmB分泌有关。

Autoantibodies in primary biliary cirrhosis:Recent progress in research on the pathogenetic and clinical significance

Primary biliary cirrhosis(PBC)is a chronic progressive cholestatic liver disease characterized by immunemediated destruction of the small-and medium-sized intrahepatic bile ducts and the presence of antimitochondrial antibodies(AMA)in the serum.AMA are detected in over 90%of patients with PBC,whereas their prevalence in the general population is extremely low,varying from 0.16%to 1%.Previous studies have shown that the unique characteristics of biliary epithelial cells undergoing apoptosis may result in a highly direct and very specific immune response to mitochondrial autoantigens.Moreover,recent studies have demonstrated that serum from AMA-positive PBC patients is reactive with a number of xenobiotic modified E2 subunits of the pyruvate dehydrogenase complex,which is not observed in the serum of normal individuals.These findings indicate that chemicals originating from the environment may be associated with a breakdown in the tolerance to mitochondrial autoantigens.While it is currently generally accepted that AMA are the most specific serological markers of PBC,more than 60 au-toantibodies have been investigated in patients with PBC,and some have previously been considered specific to other autoimmune diseases.This review covers the recent progress in research on the pathogenetic and clinical significance of important autoantibodies in PBC.Determining the pathogenic role of those autoantibodies in PBC remains a priority of basic and clinical research.

基于特征信息融合预测Anti-CRISPR蛋白

CRISPR-Cas系统是一种存在于细菌和古细菌中的获得性免疫系统,作为基因编辑工具在癌症治疗等方面被广泛研究,但CRISPR-Cas基因编辑技术存在基因脱靶效应。研究发现,Anti-CRISPR蛋白是一种可以调节CRISPR-Cas系统功能的蛋白质,在不破坏靶向基因编辑的情况下,可以减少脱靶效应等不良影响,从而提高基因编辑技术的效率和安全性。因此,研究Anti-CRISPR蛋白对于理解CRISPR-Cas系统的功能和细菌-病毒相互作用具有重要意义。本文构建了Anti-CRISPR蛋白数据集,提取氨基酸组分、氨基酸二肽组分、g-gap二肽组成、蛋白质二级结构、平均化学位移和蛋白质骨架6种特征参数,利用支持向量机对Anti-CRISPRs蛋白进行预测,在Jackknife检验下,单特征参数最高预测成功率为93.50%;对维度过高的氨基酸二肽组分和g-gap二肽组成分别进行降维处理,得到g-gap二肽组成在g=3、维数是121维时预测成功率最高,为95.10%,进一步研究发现有16种g-gap二肽组合对应11种氨基酸与Anti-CRISPR蛋白预测相关度较大;最后对特征参数进行融合,融合后最高预测成功率为96.07%。

Fractal Laser Cone Structures Proposed to Confine Antimatter

Flat, straight sheets of paper, standing vertically on edge cannot support any load placed upon their top edge, but once formed into fractal tube conic sections, they have been measured to support up to 97.52 (± 2.27) kilograms (215 (± 5) pounds) of weight with strength-per-weight ratio up to 10,336 (± 240). So, strength has been discovered to be an emergent characteristic arising solely from addition of intelligent order. It is proposed to impose such intelligent order upon, preferably, at least 6 laser beams by focusing each of them to form cones of light, arranging the cones to form a wall of a larger fractal cone, and converging all of them to a common focal point inside a vacuum chamber to give them sufficient strength near this focal point to attract, hold, and move neutral antimatter, preferably anti-lithium. This opens the new field of structural engineering of light and re-defines the concept of strength. Means of cancelling out radiation pressure by reflection of laser beams back to the common focal point are proposed to enable laser confinement of particles having low polarizability, such as anti-hydrogen. Counter-circulation of light by reflection at grazing incidence is proposed as a means of returning escaping antimatter back to the common focal point containment area. Means are proposed to inject a stream of matter into the contained antimatter to create a matter-antimatter reactor and propulsion engine. Since anti-lithium is not available, yet, means are proposed to test these structures by confining ordinary lithium, instead, and by hitting it with anti-protons and/or positrons. Means are proposed to modulate the matter-antimatter reaction with information to create modulated gravitational waves for communication. The proposed structures would enable efficient, stable, safe confinement of antimatter, which would allow better study of antimatter, and make possible renewable, clean, safe, matter-antimatter reactor generators and propulsion engines, antimatter-assisted fusion reactors, and modulated gravitational wave generators.

Autoimmune liver disease-related autoantibodies in patients with biliary atresia

AIM To investigate the prevalence and clinical significance of autoimmune liver disease(ALD)-related autoantibodies in patients with biliary atresia(BA).METHODS Sera of 124 BA patients and 140 age-matched non-BA controls were assayed for detection of the following autoantibodies: ALD profile and specific anti-nuclear antibodies(ANAs), by line-blot assay; ANA and antineutrophil cytoplasmic antibody(ANCA), by indirect immunofluorescence assay; specific ANCAs and antiM2-3 E, by enzyme linked immunosorbent assay. Associations of these autoantibodies with the clinical features of BA(i.e., cytomegalovirus infection, degree of liver fibrosis, and short-term prognosis of Kasai procedure) were evaluated by Spearman's correlation coefficient.RESULTS The overall positive rate of serum autoantibodies in preoperative BA patients was 56.5%. ALD profile assay showed that the positive reaction to primary biliary cholangitis-related autoantibodies in BA patients was higher than that to autoimmune hepatitis-related autoantibodies. Among these autoantibodies, anti-BPO was detected more frequently in the BA patients than in the controls(14.8% vs 2.2%, P < 0.05). Accordingly, 32(25.8%) of the 124 BA patients also showed a high positive reaction for anti-M2-3 E. By comparison, the controls had a remarkably lower frequency of anti-M2-3 E(P < 0.05), with 6/92(8.6%) of patients with other liver diseases and 2/48(4.2%) of healthy controls. The prevalence of ANA in BA patients was 11.3%, which was higher than that in disease controls(3.3%, P < 0.05), but the reactivity to specific ANAs was only 8.2%. The prevalence of ANCAs(ANCA or specific ANCAs) in BA patients was also remarkably higher than that in the healthy controls(37.9% vs 6.3%, P < 0.05), but showed no difference from that in patients with other cholestasis. ANCA positivity was closely associated with the occurrence of postoperative cholangitis(r = 0.61, P < 0.05), whereas none of the autoantibodies showed a correlation to cytomegalovirus infection or the stages of liver fibrosis.CONCLUSION High prevalence of autoantibodies in the BA developmental process strongly reveals the autoimmunemediated pathogenesis. Serological ANCA positivity may be a useful predictive biomarker of postoperative cholangitis.

Discovery of potent anti-MRSA components from Dalbergia odorifera through UPLC-Q-TOF-MS and targeting PBP2a protein through in-depth transcriptomic,in vitro,and in-silico studies

Methicillin-resistant Staphylococcus aureus(MRSA)is an important pathogen casting dire shadow over global human wellbeing[1].Rising antibiotic resistance in MRSA led to research into plant-derived anti-microbial agents.Approximately 119 compounds from 90 plants were recognized as potent anti-bacterials[2].Dalbergia odorifera,a traditional Chinese plant,has demonstrated anti-tumor,anti-microbial,anti-inflammatory,and cardiovascular protective effects[3].Limited studies have explored D.odorifera flavonoids'inhibitory activity against MRSA.Transcriptomics,a high-throughput method,aided in comprehending plant antibacterial therapy by generating data for gene expression,target identification,and pathway analysis[4].Consequently,our study aimed to assess D.odorifera's anti-MRSA effects and reveal its material foundation and antibacterial mechanism by ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS),and transcriptomic analysis,in vitro,and in-silico studies.

Assessment of Liver Fibrosis in HBsAg-Negative and Anti HBc Positive Patients

Background: Surface antigen (HBsAg) is the mean marker of hepatitis B virus infection. During the course of the infection, some patients lose the HBsAg and only the presence of anti-HBc antibody indicates previous contact with the virus. Among these patients, some have detectable viral load (occult infection) but most without viral replication. There is no guideline regarding these patients. The aim of this study was to assess hepatic fibrosis in patients with only the hepatitis B virus contact marker “total anti-HBc”. Patients and methods: it was a descriptive and analytical cross-sectional study, conducted in three private hospitals from January to August 2022. Were included HBsAg-negative and HBc-positive patients, consulting in Gastroenterology departments. Noninvasive methods (APRI, FIB-4 and FIBROSCAN) were used to evaluate liver stiffness because of their easy accessibility and low-cost. The hepatic fibrosis was considered significant when the score determined by APRI, FIB-4 and FIBROSCAN® tests was respectively greater than 1.5;2.67 and 8 kPa corresponding to fibrosis level 2 (F2). Results: A total of 63 HBsAg-negative/total HBcAg-positive patients were included. The mean age was 49.9 ± 13.4 years. The male/female sex ratio was 1.78. Of the 63 patients, 19 had significant liver fibrosis (30.1%) among which 9 patients had HCC. The FIB-4 score outperformed the APRI score in assessing liver fibrosis, with a sensitivity of 84.2%, a specificity of 100% and a negative predictive value of 93.6%. In univariate analysis, there was a significant association between the occurrence of significant liver fibrosis and age over 40 years, dyslipidaemia, obesity, alcohol consumption, smoking, herbal medicine, negative anti-HBs immunological status and detectable viral load. Conclusion: Our study revealed a high prevalence of significant to severe hepatic fibrosis in anti-HBc positive patients. In most of the cases, the fibrosis was severe. Progression to HCC has also been possible. There is no consensus on the follow-up strategy for those patients. However, screening for hepatic fibrosis using noninvasive methods should be recommended for patients aged over 40 years, alcohol or herbal medicine users, patients with metabolic syndrome or occult hepatitis B. In HBsAg-negative/anti-HBc-positive patients, liver stiffness should be evaluated and if it is greater than F2, HCC screening should be started.

Simultaneous Dual Selective Targeted Delivery of Two Covalent Gemcitabine Immunochemotherapeutics and Complementary Anti-Neoplastic Potency of [Se]-Methylselenocysteine

The anti-metabolite chemotherapeutic, gemcitabine is relatively effective for a spectrum of neoplastic conditions that include various forms of leukemia and adenocarcinoma/carcinoma. Rapid systemic deamination of gemcitabine accounts for a brief plasma half-life but its sustained administration is often curtailed by sequelae and chemotherapeutic-resistance. A molecular strategy that diminishes these limitations is the molecular design and synthetic production of covalent gemcitabine immunoche-motherapeutics that possess properties of selective “targeted” delivery. The simultaneous dual selective “targeted” delivery of gemcitabine at two separate sites on the external surface membrane of a single cancer cell types represents a therapeutic approach that can increase cytosol chemotherapeutic deposition;prolong chemotherapeutic plasma half-life (reduces administration frequency);minimize innocent exposure of normal tissues and healthy organ systems;and ultimately enhance more rapid and thorough resolution of neoplastic cell populations. Materials and Methods: A light-reactive gemcitabine intermediate synthesized utilizing succinimidyl 4,4-azipentanoate was covalently bound to anti-EGFR or anti-HER2/neu IgG by exposure to UV light (354-nm) resulting in the synthesis of covalent immunoche-motherapeutics, gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu]. Cytotoxic anti-neoplastic potency of gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] between?gemcitabine-equivalent concentrations of 10-12 M and 10-6 M was determined utilizing chemotherapeutic-resistant mammary adenocarcinoma (SKRr-3). The organoselenium compound, [Se]-methylselenocysteine was evaluated to determine if it complemented the anti-neoplastic potency of the covalent gemcitabine immunoche-motherapeutics. Results: Gemcitabine-(C4-amide)-[anti-EGFR], gemcitabine-(C4-amide)-[anti-HER2/neu] and the dual simultaneous combination of gemcitabine-(C4-amide)-[anti-EGFR] with gemcitabine-(C4-amide)-[anti-HER2/neu] all had anti-neoplastic cytotoxic potency against mammary adenocarcinoma. Gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] produced progressive increases in anti-neoplastic cytotoxicity that were greatest between gemcitabine-equivalent concentrations of 10-9 M and 10-6 M. Dual simultaneous combinations of gemcitabine-(C4-amide)-[anti-EGFR] with gemcitabine-(C4-amide)-[anti-HER2/neu] produced levels of anti-neoplastic cytotoxicity intermediate between each of the individual covalent gemcitabine immunochemotherapeutics. Total anti-neoplastic cytotoxicity of the dual simultaneous combination of gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] against chemothe-rapeutic-resistant mammary adenocarcinoma (SKBr-3) was substantially higher when formulated with [Se]-methylsele-no-cysteine.

Tumor-infiltrating T-Lymphocyte immunity-related immune tolerance and anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy for advanced hepatocellular carcinoma

Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes remain a concern.With increasing exploration of the HCC microenvironment,particularly in terms of T lymphocyte immunity,a new era of immunomolecular targeted therapy,based on molecular signaling,has arrived for advanced HCC.In the study of immune tolerance of the intrinsic HCC microenvironment,we found that multiple immunosuppressive mechanisms and immune checkpoint inhibitors,such as anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy,have improved clinical outcomes in some patients with advanced HCC.Furthermore,various combination therapies have been investigated,and HCC types have been categorized into different types based on anti–programmed cell death protein 1(PD-1)/ligand of programmed cell death protein 1(PD-L1)treatment.In this paper,we first discuss the tumor-infiltrating T lymphocyte immunity and immune tolerance of HCC.We then clarify the basic mechanism of anti–PD-1/PD-L1 therapy and discuss the types of HCC based on anti–PD-1/PD-L1 therapy.Thereafter,we explain the relevant studies and mechanisms of combination therapy of anti–PD-1/PD-L1 with antiangiogenesis drugs or multikinase kinase inhibitors,anti–T lymphocyte–related signaling pathways in HCC,and other anti-CD8+T cell immune checkpoints.In this way,this review offers a deeper understanding of anti–PD-1/PD-L1 immunotherapy for advanced HCC,in order to provide better individualized treatments for patients with advanced HCC.

轮图中三类特殊子图的anti-Ramsey数

在边染色图中,如果某个子图的每条边都染不同的颜色,则称该子图是彩虹的。给定图G和H,对图G的一个k边染色若存在最大的正整数R,使得G中不包含彩虹的H作为子图,则将H的anti-Ramsey数记为ar(G,H)。当主图为轮图时,给出了Theta图、星图和双星图anti-Ramsey数的精确值。

Antibody Pattern: Correlation of Age and Gender in ANA and Anti-ds-DNA Prevalence

The study was designed to find the prevalence of ANA antibodies and anti-dsDNA antibodies in samples tested at AFIP Rawalpindi and their correlation with age and gender and to find positive and negative predictive values of ANA antibodies.For this purpose,twelve thousand nine hundred sixty-seven(12,967)patients were analyzed for ANA with four hundred sixty-eight(468)healthy samples tested as control and four thousand seven hundred three(4,703)patients tested for ds-DNA antibodies.Retrospective data of all samples tested by indirect immunofluorescence(IF)for ANA antibodies and dsDNA antibodies was collected.To address positive and negative predictive values another control group(autoimmunity not suspected)of serum samples was taken from the healthy population.For the first group,age,gender,ANA antibodies and ds-DNA antibodies results(both tests performed by IIF)data was collected from a computer record cell;for the second control group,ANA antibodies were performed by IIF.12,967 and 4,703 samples(Group 1)were tested for ANA antibodies and dsDNA antibodies,respectively,during this period.1,119(9%)and 99(2%)were found positive for ANA antibodies and ds DNA antibodies.Among these positive samples,850(76%)and 73(74%)were females respectively.Gender predisposition towards autoimmunity(ANA)was found significant with a P value of(P=0.001).Relation of age was also found significant with anti-ANA antibodies with a P value of(P=0.001).This study shows a negative correlation between age(P=0.025)and gender(P=0.001)with anti-dsDNA which is also significant.High prevalence was found below the mean age of 38 years(SD±16.635)for ANA antibodies and the mean age of 35 years(SD±15.066)for ds-DNA antibodies.The age of ANA antibodies and dsDNA antibodies positive patients ranged from 1 year old to 98 years old and 2 years old to 95 years old respectively.In the second(autoimmunity-free)control group,a total of 468 samples were tested for ANA antibodies and 9(2%)were found positive.Positive predictive value(PPV)was 8.6%and negative predictive value(NPV)was 98%.ANA is a sensitive test for autoimmunity and it is significantly related to female gender and increasing age.The low prevalence of ANA antibodies among clinically suspected cases suggests that rationalization of test prescriptions is needed.Anti-ds-DNA is also a sensitive test for diagnosis of SLE and it is significantly related to female gender and increasing age.