Potentilla anserine L. polysaccharide protects against cadmium-induced neurotoxicity

Cadmium is a toxic metal that can damage the brain and other organs. This study aimed to explore the protective effects of Potentilla anserine L. polysaccharide (PAP) against CdCl₂-induced neurotoxicity in N2a and SH-SY5Y cells and in the cerebral cortex of BALB/c mice. In addition, we aimed to identify the potential mechanisms underlying these protective effects. Relative to CdCl₂ treatment alone, pretreatment with PAP prevented the reduction in cell viability evoked by CdCl₂, decreased rates of apoptosis, promoted calcium homeostasis, decreased ROS accumulation, increased mitochondrial membrane potential, inhibited cytochrome C and AIF release, and prevented the cleavage of caspase-3 and PARP. In addition, PAP significantly decreased the CdCl₂-induced phosphorylation of CaMKII, Akt, and mTOR. In conclusion, PAP represents a potential therapeutic agent for the treatment of Cd-induced neurotoxicity, functioning in part via attenuating the activation of the mitochondrial apoptosis pathway and the Ca²⁺-CaMKII-dependent Akt/mTOR pathway.     

Out of the boxes,out of the silos: The need of interdisciplinary collaboration to reduce poor-quality medical products in the supply chain

In this paper, we argue that understanding and addressing the problem of poor-quality medical products requires a more interdisciplinary approach than has been evident to date. While prospective studies based on rigorous standardized methodologies are the gold standard for measuring the prevalence of poor-quality medical products and understanding their distribution nationally and internationally, they should be complemented by social science research to unpack the complex set of social, economic, and governance factors that underlie these patterns. In the following sections, we discuss specific examples of prospective quality surveys and of social science studies, highlighting the value of cross-sector partnerships in driving high-quality, policy-relevant research in this area.     

海南地不容生物碱抑制肿瘤细胞增殖及构效关系解析

目的研究海南地不容(Stephania hainanensis H.S.Lo et Y.Tsoong)生物碱对人肝癌细胞Hep G-2、乳腺癌细胞MCF-7、胃癌细胞SGC-7901增殖的影响,筛选出有效的抗肿瘤化合物以及其敏感细胞株;分析其生物碱的构效关系。方法采用MTT法检测不同浓度的海南地不容生物碱对人肝癌细胞Hep G-2、乳腺癌细胞MCF-7、胃癌细胞SGC-7901增殖的抑制率;通过查阅国内外相关文献,分析海南地不容生物碱抗肿瘤活性的基本构效关系。结果MTT结果显示荷包牡丹碱、氧化克班宁、去甲荷包牡丹碱和克班宁对人肝癌Hep G-2、乳腺癌MCF-7和胃癌SGC-7901细胞的增值分别具有不同程度的剂量依赖性的抑制作用,各给药组分吸光度值与空白对照组比具有显著性差异(P<0.01),与阳性对照比较无明显统计学差异(P>0.05);海南地不容生物碱结构中的1,2-亚甲二氧基、N-亚甲基等取代基以及其化学结构的平面性对其抗肿瘤活性有重要影响。结论海南地不容中具有明显抗肿瘤作用的生物碱为荷包牡丹碱、氧化克班宁、去甲荷包牡丹碱和克班宁,其敏感细胞株均为乳腺癌细胞MCF-7;通过分析海南地不容生物碱的结构和抗肿瘤活性的关系,初步明确了其抗肿瘤活性可能与其结构易于抑制DNA拓扑异构酶和诱导细胞凋亡有关。     

Prevalence of Stroke in Fayoum Governorate,Egypt: A Community-Based Study

Background: Stroke is a highly prevalent disease with consequent mortality and morbidity. Few community based studies have been conducted only in upper Egypt to estimate prevalence of stroke. Objectives: This study was designed to find out the prevalence of stroke in Fayoum Governorate & to study some associated risk factors. Methods: through this community based cross-sectional study 4784 participants aged more than or equal to 18 years old were enrolled. A multi-stage random sample technique was followed to choose the study sample. A predesigned interviewer-administered structured questionnaire was used. Suspected stroke case by screening questionnaire was referred to the neurologist. Results: The Crude prevalence of stroke was 16 out of 1000 with confidence interval of proportion (12.6%-19.7%). The age adjusted local (Fayoum 2017 census) prevalence rate was 7.97 out of 1000, age adjusted prevalence rate (Egypt population 2017) was 1.05 out of 1000. Age-adjusted World Health Organization standard world population prevalence rate was 1.69 out of 1000. The crude prevalence of ischemic stroke was significantly higher than hemorrhagic stroke 11.9 versus 3.9 out of 1000 population. The most prevalent risk factor was smoking among males, followed by obesity then hypertension. The prevalence of stroke was significantly higher among participants affected with hypertension, diabetes, heart diseases, obesity, and smoking. Logistic regression analysis showed that having hypertension, diabetes, heart diseases, atrial fibrillation, obesity, and smoking were reported risk factors of stroke. Conclusions: The prevalence of stroke in Fayoum governorate was 1.6%. Hypertension, diabetes, heart diseases, obesity, and smoking were reported risk factors of stroke.     

Neuropeptides Profile and Increased Innervation in Becker's Nevus

BackgroundMelanocytes are derived from neural crest, and various pigmentary disorders may accompany abnormalities in nerve system or develop following dermatome, suggesting that melanocyte and pigmentation may be closely related to neural factors. There are reports of Becker''s nevus (BN) showing linear and segmental configuration, suggesting the association of BN with nerve system. However, there are no studies regarding the expression of neuropeptides in BN.ObjectiveWe investigated the expression of neuropeptides and innervation in BN.MethodsPolymerase chain reaction (PCR) array of 84 genes related to neuronal process was done. Among the genes with 10-fold or more increase in lesional, real-time PCR was performed for neuropeptide Y (NPY), galanin, neurotensin (NTS) and their receptors skin compared to normal skin. IHC stain was done to look for the expression of NPY, galanin, NTS and their receptors and the distribution of protein gene products (PGP) 9.5 immunoreactive nerve fibers.ResultsPCR array revealed that 16 out of 84 genes related to neuronal process were increased by 10-fold or more in lesional skin. In real-time PCR of NPY, galanin, NTS and their receptors, statistically significant increase of NPY1R (p<0.05) and marginally significant increase of NPY2R, GAL2R, and NTS2R (p<0.1) was verified in lesional skin. In immunohistochemistry, NPY, NPY1R NPY2R, and NTS2R were highly expressed in lesional skin and increased PGP 9.5 immunoreactive linear nerve fibers were found in the epidermis of BN.ConclusionNPY, galanin, NTS and their receptors and increased innervation may play a role in the pathogenesis of BN.     

Safety data from the MenB-FHbp clinical development program in healthy individuals aged 10 years and older

BackgroundThe MenB-FHbp vaccine (Trumenba®) is licensed in various countries for the prevention of meningococcal serogroup B disease in individuals ≥ 10 years of age. The clinical development program included 11 completed trials where, in each trial, MenB-FHbp had an acceptable safety profile after a primary vaccination series was administered to individuals 10–65 years of age. However, the detection of potential rare events was limited because of individual clinical trial size. The current safety analysis evaluates pooled reactogenicity and other adverse events (AEs) reported in these trials to identify new safety signals not detectable in individual trials.MethodsEleven trials contributed safety data, of which 10 recorded local and systemic reactogenicity events; 8 of the trials were controlled, and reactogenicity data were pooled for 7 of these 8 trials. Additional AE evaluations included immediate AEs (IAEs), medically attended AEs (MAEs), serious AEs (SAEs), newly diagnosed chronic medical conditions (NDCMCs), and autoimmune or neuroinflammatory conditions.ResultsLocal and systemic reactions were more frequent in the MenB-FHbp group (n = 15,294) compared with controls (n = 5509), although most reactions were transient and mild to moderate in severity. Frequencies of IAEs, SAEs, MAEs, NDCMCs, and autoimmune or neuroinflammatory conditions were similar between the MenB-FHbp and control groups.ConclusionsMenB-FHbp demonstrated a favorable safety and tolerability profile in the clinical development program of > 15,000 vaccine recipients ≥ 10 years of age. No new safety signals were identified in the pooled analysis compared with data from the individual trials. Continued postmarketing safety surveillance is important for the identification of rare events.Clinicaltrials.gov: NCT01299480; NCT000808028; NCT00879814; NCT00780806; NCT01352845; NCT01352793; NCT01461993; NCT01323270; NCT01830855; NCT01461980; NCT01768117.     

Pleomorphic mastocytoma associated with loss of chromosome 5, PDGFRA,and HRAS mutations: A case of cutaneous mastocytosis with severe atypia and indolent behavior

A 21‐year‐old female presented with a 5‐year history of an erythematous papule on her right breast. The biopsy showed a dense, dermal nodular infiltrate, extending focally into the subcutaneous tissue. The infiltrate was composed predominantly of pleomorphic cells with bi‐lobed, multi‐lobed, horseshoe, or ring‐shaped nuclei. There was a smaller subset of monomorphous cells characterized by a round, reniform, or elongated single‐lobed nucleus. Accompanying cells included few foamy histiocytes, lymphocytes, and numerous scattered eosinophils. No necrosis, vascular invasion, or ulceration was present. The pleomorphic and monomorphic granular cells were positive for Giemsa stain as well as for tryptase, CD117, CD68, CD2, and CD30 immunohistochemistry and negative for S100, CD1a, myeloperoxidase, lysozyme, and CD56. Clinical examination was negative for any additional similar lesions and serum tryptase was within normal limits. The bone marrow was not biopsied. In addition, fluorescent in situ hybridization revealed multiple clones with loss of number 5 chromosome and PDGFRA and HRAS mutations. The lesion did not recur or progress after a 6‐year clinical follow‐up. To our full knowledge, we report the first case of pleomorphic mastocytoma with loss of chromosome 5 and PDGFRA and HRAS mutations.