RESUMO
Brain edema belongs to the category of "stroke" and "true headache", while Traditional Chinese Medicine mostly understands its core disease mechanisms from the perspectives of stasis, deficiency, and heat, and mostly treats the disease by using warming yang to induce diuresis and eliminating stasis to remove water. Wuling Powder has been lauded as the "first party to typhoid and relieving diuresis", which is used to cure clearing damp and promoting diuresis and warming yang and transforming qi, and has been clinically used in the treatment of brain edema caused by various causes such as head trauma, intracerebral hemorrhage, cerebral infarction, and intracranial space occupying, all with remarkable efficacy. Wuling Powder improves cellular energy supply, scavenges excess oxygen radicals and calcium ions in brain tissue, and reduces the damage to brain tissue caused by vascular inflammatory factors and regulates aquaporins and vascular endothelial growth factor, thereby achieving therapeutic effects.
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BackgroundSolid organ transplant recipients (SOTR), who typically receive post-transplant immunosuppression, show increased COVID-19-related mortality. It is unclear whether an additional dose of COVID-19 vaccines in SOTR can overcome the reduced immune responsiveness against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants. MethodsWe performed a prospective cohort study of 53 SOTR receiving SARS-CoV-2 vaccination into a prospective cohort study performing detailed immunoprofiling of humoral immune responses against SARS-CoV-2 and its variants. ResultsPrior to the additional vaccine dose, 60.3% of SOTR showed no measurable neutralization and only 18.9% demonstrated neutralizing activity of >90% following two vaccine doses. More intensive immunosuppression, antimetabolites in particular, negatively impacted antiviral immunity. While absolute IgG levels were lower in SOTR than controls, antibody titers against microbial recall antigens were in fact higher. In contrast, SOTR showed reduced vaccine-induced IgG/IgA antibody titers against SARS-CoV-2 and its delta variants. Vaccinated SOTR showed a markedly fewer linear B cell epitopes, indicating reduced B cell diversity. Importantly, a third vaccine dose led to an increase in anti-SARS-CoV-2 antibody titers and neutralizing activity across alpha, beta and delta variants. However, we observed a significant decrease in anti-spike antibody titers with the omicron variant. ConclusionsOnly a small subgroup of SOTR generated functionally relevant antibodies after completing the initial vaccine series based on dysfunctional priming of immune responses against novel antigens. An additional dose of the vaccine results in dramatically improved antibody responses against all SARS-CoV-2 variants except omicron.
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Glioma is the most common primary malignancy of the central nervous system and is associated with high mortality rates. Despite the available treatment options including surgery, radiotherapy and chemotherapy, the median patient survival rate is low. Therefore, the development of novel anticancer agents for the treatment of glioma is urgently required. Tanshinone I (TS I) is a tanshinone compound that is isolated from Danshen. Accumulating evidence indicates that TS I exhibits antiproliferative activity in a variety of cancer types. However, the role of TS I and its mechanism of action in human glioma remain to be elucidated. In the present study, the anticancer potential of TS I against human glioma U87 MG cells was investigated. The results indicated that TS I exerted a potential cytotoxic effect on human glioma U87 MG cells. TS I was found to induce cell proliferation, inhibition, cell cycle arrest, apoptosis and autophagy in U87 MG cells. Mechanistic experiments indicated that TS I activated endoplasmic reticulum (ER) stress and inhibited AKT signaling and apoptosis in human glioma U87 MG cells. Furthermore, the present study demonstrated that TS I induced protective autophagy in U87 MG cells. Additionally, ER stress and AKT signalmediated apoptosis and protective autophagy were found to be induced by TS I via intracellular reactive oxygen species accumulation. The results of the present study demonstrated that TS I may be a potential anticancer drug candidate that may be of value in the treatment of human glioma.
Assuntos
Abietanos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Glioma , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Glioma/tratamento farmacológico , Glioma/metabolismo , Glioma/patologia , HumanosRESUMO
Synaptosomes were isolated from pig brain by homogenization, differential centrifugation and sucrose gradient centrifugation. After synaptosome lysis in hypoosmotic buffer, the plasma membrane vesicles were collected. Following the solubilization of plasma membrane vesicles in Triton X-100, the solubilized protein was applied to calmodulin affinity chromatography colurnn, and the delipidated plasma membrane Ca2 + -ATPase was purified to nearly homogeneity. The novel feature of this purification is the use of large affinity column and heavy washing to facilitate the purified Ca2+ -ATPase with higher activity and protein yield. The specific activity of the purified Ca2+ -ATPase was recovered to a maximum of 3.32 μmol· mg-1· min-1 after incubation with asolectin. Silver staining of SDS-PAGE revealed a single protein band around Mr 140 000, showing the purity was over 90 %. Different Ca2 + concentrations dramatically affect the specific activity of Ca2 + -ATPase.