Angiotensin (1−7) peptide replacement therapy with plasma transfusion in COVID-19

AimTo determine whether convalescent angiotensin (1?7) peptide replacement therapy with plasma (peptide plasma) transfusion can be beneficial in the treatment of critically ill patients with severe coronavirus 2 (SARS-CoV-2) infection.Study designCase series of 9 critically ill patients with laboratory-confirmed COVID-19 who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment.Peptide plasma: Plasma with angiotensin (1?7) content 8–10 times higher than healthy plasma donors was obtained from suitable donors. Peptide plasma transfusion was applied to 9 patients whose clinical status and/or laboratory profile deteriorated and who needed intensive care for 2 days.ResultsIn our COVID-19 cases, favipiravir, low molecular weight heparin treatment, which is included in the treatment protocol of the ministry of health, was started. Nine patients with oxygen saturation of 93% and below despite nasal oxygen support, whose clinical and/or laboratory deteriorated, were identified. The youngest of the cases was 36 years old, and the oldest patient was 85 years old. 6 of the 9 cases had male gender. 3 cases had been smoking for more than 10 years. 4 cases had at least one chronic disease.In all of our cases, SARS CoV2 lung involvement was bilateral and peptide plasma therapy was administered in cases when oxygen saturation was 93% and below despite nasal oxygen support of 5 liters/minute and above, and intensive care was required. Although it was not reflected in the laboratory parameters in the early period, 8 patients whose saturations improved with treatment were discharged without the need for intensive care. However, a similar response was not obtained in one case. Oxygen requirement increased gradually and, he died in intensive care process. An increase of the platelet count was observed in all cases following the peptide plasma treatment.ConclusionIn this preliminary case series of 9 critically ill patients with COVID-19, administration of plasma containing angiotensin (1?7) was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.     

中成药联合普利或沙坦类药物治疗糖尿病肾病的网状Meta分析＊

目的 运用网状Meta分析方法，以单纯ACEI/ARB（angiotensin receptor blockers，ARB；angiotensin-converting enzyme inhibitor，ACE）治疗为共同参照，对比海昆肾喜胶囊、黄葵胶囊、尿毒清颗粒、肾衰宁胶囊、雷公藤多苷片、金水宝胶囊、百令胶囊、火把花根片对糖尿病肾病的临床疗效。方法 计算机检索有关海昆肾喜胶囊、黄葵胶囊，尿毒清颗粒、肾衰宁胶囊、雷公藤多苷片、金水宝胶囊、百令胶囊、火把花根片联合ACEI/ARB治疗糖尿病肾病的随机对照试验。由2名研究人员独立筛选，包括质量、评估，数据采用R、Gemtc、ＲevMan 5.3软件进行网状Meta分析和传统Meta分析。最终纳入86篇RCTs，共7413例患者，涉及9种干预措施。结果 Meta分析结果显示：①在综合疗效方面，金水宝胶囊、雷公藤多苷片、肾衰宁胶囊联合ACEI/ARB排序靠前，其中雷公藤多苷片联合ACEI/ARB降低24 h尿蛋白（24 h UPQ）和尿微量蛋白（UAER）的疗效最佳，肾衰宁胶囊联合ACEI/ARB降低血肌酐（Scr）、糖化血红蛋白（HBA1C）和空腹血糖（FPG）的疗效最佳；②在安全性方面，联合中成药均较单纯ACEI/ARB治疗有一定改善，因临床异质性较大无法定量合并，所有纳入研究未发生严重不良反应。由于纳入文献质量相对偏低，得出的结论尚有待临床验证。结论 结合网状Meta分析结果和文献信息，在治疗有效率方面，金水宝胶囊联合ACEI/ARB疗效最优；在降低24 h尿蛋白（24 hUPQ）和尿微量蛋白（UAER）方面，均为雷公藤多苷片联合ACEI/ARB疗效最优；在降低血肌酐（Scr）、糖化血红蛋白（HBA1C）和空腹血糖（FPG）方面，均为肾衰宁胶囊联合ACEI/ARB疗效最优。     

First-in-human in vivo genome editing via AAV-zinc-finger nucleases for mucopolysaccharidosis I/II and hemophilia B

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Adsorptive removal of lead from aqueous solutions by amine–functionalized magMCM-41 as a low–cost nanocomposite prepared from rice husk: Modeling and optimization by response surface methodology

Amorphous silica that was extracted from rice husk was used to synthesize the magMCM-41 mesoporous silica. This was then functionalized by the APTMS group in order to produce NH₂-magMCM-41 as a novel and low–cost adsorbent. The XRD, VSM, N₂ adsorption–desorption, FT–IR, TGA, SEM and TEM analyses were utilized to characterize the produced materials. In order to optimize the adsorption of the Pb(II) ions, the RSM (response surface methodology) was applied by using the synthesized adsorbent in aqueous solutions. A rotatable CCD (central composite design) was adopted to carry out the experiments and RSM was used to analyze them. Three independent factors namely, initial solution pH (3–7), adsorbent dosage (0.1–2 g L^?1), and initial Pb(II) concentration (15–150 mg L^?1) were used to investigate the removal procedure. According to the obtained results, the initial solution pH of 5.22, adsorbent dosage of 0.1 g L^?1, and initial Pb(II) concentration of 150 mg L^?1 were considered as the optimum conditions with 64.32% removal of Pb(II) and an adsorption capacity of 540.64 mg g^?1. The maximum removal efficiency of Pb(II) ions was found to be 96.76%. The Sips isotherm model represents a better correlation with equilibrium data. It was reported by the kinetic study that data taken from the experiments fitted better to the pseudo–second–order model compared to the pseudo–first–order and intraparticle diffusion models. Finally, according to the thermodynamic study, the removal process strongly depends on temperature, which indicates an exothermic behavior and spontaneous nature of the adsorption.     

CD8+ T cells induced by adenovirus-vectored vaccine are capable of preventing establishment of latent murine γ-herpesvirus 68 infection

CD8+ T cells are known to control infections, but their role in preventing latent infection from establishing has not been thoroughly investigated.We hypothesized that a potent CD8+ T cell response patrolling the mucosal viral entry points could kill the first infected cells and thereby abrogate the infection before latency is established.To investigate this, replication deficient adenovirus serotype 5 vectors encoding murine γ-herpesvirus-68 CD8+ T cell epitopes linked to the T cell adjuvant Invariant chain, were developed. We show that intranasal vaccination of mice reduces the risk of establishment of latent infection from multiple intranasal ID50 challenges with murine γ-herpesvirus-68 by 81% per exposure at 14 days post vaccination. Protection waned over time, but immune responses were extended by heterologous prime-boost vaccination applied simultaneously intramuscularly and intranasally, and animals vaccinated 66 days prior to challenge showed a strong trend of long-term protection.Our data provides evidence that CD8+ T cells are able to protect against establishment of latent infection. Although the protective efficacy is difficult to maintain over time, this proof-of-concept study suggests a role for a CD8+ T cell arm in future vaccine strategies against latent human viral infections caused by pathogens such as HIV and multiple herpes virus.