Observational analysis of the immunogenicity and safety of various types of spinal muscular atrophy vaccines.

BACKGROUND: This study aimed to evaluate the immunogenicity and safety of different types of poliovirus vaccines. METHODS: A randomized, blinded, single-center, parallel-controlled design was employed, and 360 infants aged ≥ 2 months were selected as study subjects. They were randomly assigned to bOPV group (oral Sabin vaccine) and sIPV group (Sabin strain inactivated polio vaccine), with 180 infants in each group. Adverse reaction events in the vaccinated subjects were recorded. The micro-neutralization test using cell culture was conducted to determine the geometric mean titer (GMT) of neutralizing antibodies against poliovirus types I, II, and III in different groups, and the seroconversion rates were calculated. RESULTS: Both groups exhibited a 100% seropositivity rate after booster immunization. The titers of neutralizing antibodies for the three types were predominantly distributed within the range of 1:128 to 1:512. The fold increase of type I antibodies differed markedly between the two groups (P < 0.05). Moreover, the fold increase of type II and type III antibodies for poliovirus differed slightly between the two groups (P > 0.05). The fourfold increase rate in sIPV group was drastically superior to that in bOPV group (P < 0.05). When comparing the post-immunization GMT levels of type I antibodies in individuals who completed the full course of spinal muscular atrophy vaccination, bOPV group showed greatly inferior levels to sIPV group (P < 0.05). For type II and type III antibodies, individuals in bOPV group demonstrated drastically superior post-immunization GMT levels to those in sIPV group (P < 0.05). The incidence of adverse reactions between the bOPV and sIPV groups differed slightly (P > 0.05). CONCLUSION: These findings indicated that both the oral vaccine and inactivated vaccine had good safety and immunogenicity in infants aged ≥ 2 months. The sIPV group generated higher levels of neutralizing antibodies in serum, particularly evident in the post-immunization GMT levels for types II and III.

Targeting copper metabolism: a promising strategy for cancer treatment.

Copper is an essential micronutrient that plays a critical role in many physiological processes. However, excessive copper accumulation in cancer cells has been linked to tumor growth and metastasis. This review article explores the potential of targeting copper metabolism as a promising strategy for cancer treatment. Excessive copper accumulation in cancer cells has been associated with tumor growth and metastasis. By disrupting copper homeostasis in cancer cells and inducing cell death through copper-dependent mechanisms (cuproplasia and cuprotosis, respectively), therapies can be developed with improved efficacy and reduced side effects. The article discusses the role of copper in biological processes, such as angiogenesis, immune response, and redox homeostasis. Various approaches for targeting copper metabolism in cancer treatment are examined, including the use of copper-dependent enzymes, copper-based compounds, and cuprotosis-related genes or proteins. The review also explores strategies like copper chelation therapy and nanotechnology for targeted delivery of copper-targeting agents. By understanding the intricate network of cuprotosis and its interactions with the tumor microenvironment and immune system, new targets for therapy can be identified, leading to improved cancer treatment outcomes. Overall, this comprehensive review highlights the significant potential of targeting copper metabolism as a promising and effective approach in cancer treatment, while providing valuable insights into the current state of research in this field.

Role of Phosphatidylinositol 3-Kinase and Its Catalytic Unit PIK3CA in Cervical Cancer: A Mini-Review.

In complicated disorders like cancer, signaling pathways form a tangled network. Targeting one gene may result in an unfavorable reaction from another off-target gene. Such entwined complexities may result in treatment resistance or failure in cancer patients. The PI3K/Akt/mTOR (phosphoinositol 3-kinase/protein kinase B/mammalian target of rapamycin) pathway is dysregulated in cervical cancer and is used as a biomarker for therapy. PI3K is a kinase that consists of a regulatory and catalytic domain and has phosphorylation capability. Class I components like the catalytic part (PIK3CA and PIK3CD) and regulatory part (like PIK3R1, PIK3R2, PIK3R3, and PIK3R5) are associated with oncogenesis and growth factors in cervical cancer. This review is aimed at discussing the involvement of the PI3K component of the PI3K/Akt/mTOR network in cervical cancer. Specifically, class I catalytic subunit PIK3CA has been identified as a pharmacological target, making it therapeutically significant. Apart from discussing the function of PI3K and PIK3CA in cervical cancer, we also discuss their inhibitors, which may be beneficial in treating cervical cancer.

The Traditional Uses, Phytochemistry and Pharmacology of Sarcandra glabra (Thunb.) Nakai, a Chinese Herb With Potential for Development: Review.

Sarcandra glabra (Thunb.) Nakai is a folk medicine with a long history in China, which has been applied to treat sore throat, abscess, even tumor and so on. Meanwhile, it is also used as tea in some areas. At present, more than 200 chemical compounds have been isolated and identified from it, such as, sesquiterpenes, flavonoids, phenolic acids, coumarins and so on. Pharmacological studies have already confirmed that the extracts of S. glabra have many effects, such as antibacterial, antiviral, anti-inflammatory, anti-tumor, and anti-thrombocytopenia, especially the effects of anti-tumor and anti-thrombocytopenia are confirmed in clinic. Therefore, this paper systematically summarized the traditional uses, botany, phytochemistry, pharmacology, and toxicity of S. glabra, in order to provide a beneficial reference of its further research.

Polygonum perfoliatum L., an Excellent Herbal Medicine Widely Used in China: A Review.

Polygonum perfoliatum L. (synonym: Polygonum knotweed L.; Persicaria perfoliata; family: Polygonaceae) is a kind of folk traditional Chinese medicine with a long history of wide use in the treatment of ancient internal, surgical, and gynecological diseases. At present, 80 chemical constituents have been isolated from P. perfoliatum, including flavonoids, anthraquinones, terpenoids, phenolic acids, phenylpropanoids, and alkaloids, among which flavonoids are the main active components. Modern studies have shown that P. perfoliatum has pharmacological activities such as anti-inflammatory, anti-bacterial, antiviral, anti-liver fibrosis, antitussive and expectorant, anti-tumor, anti-oxidation, and so on. By consulting and sorting out a large number of related literatures at home and abroad in recent years, this paper systematically reviewed the botany, traditional uses, phytochemistry, pharmacological activities, and quality control of P. perfoliatum, and discussed its development potential in new drug research and clinical application in the future, in order to provide a reference basis for further research and promote the in-depth development and utilization.

The Spontaneous Activity Pattern of the Middle Occipital Gyrus Predicts the Clinical Efficacy of Acupuncture Treatment for Migraine Without Aura.

The purpose of the present study was to explore whether and to what extent the neuroimaging markers could predict the relief of the symptoms of patients with migraine without aura (MWoA) following a 4-week acupuncture treatment period. In study 1, the advanced multivariate pattern analysis was applied to perform a classification analysis between 40 patients with MWoA and 40 healthy subjects (HS) based on the z-transformed amplitude of low-frequency fluctuation (zALFF) maps. In study 2, the meaningful classifying features were selected as predicting features and the support vector regression models were constructed to predict the clinical efficacy of acupuncture in reducing the frequency of migraine attacks and headache intensity in 40 patients with MWoA. In study 3, a region of interest-based comparison between the pre- and post-treatment zALFF maps was conducted in 33 patients with MwoA to assess the changes in predicting features after acupuncture intervention. The zALFF value of the foci in the bilateral middle occipital gyrus, right fusiform gyrus, left insula, and left superior cerebellum could discriminate patients with MWoA from HS with higher than 70% accuracy. The zALFF value of the clusters in the right and left middle occipital gyrus could effectively predict the relief of headache intensity (R 2 = 0.38 ± 0.059, mean squared error = 2.626 ± 0.325) and frequency of migraine attacks (R 2 = 0.284 ± 0.072, mean squared error = 20.535 ± 2.701) after the 4-week acupuncture treatment period. Moreover, the zALFF values of these two clusters were both significantly reduced after treatment. The present study demonstrated the feasibility and validity of applying machine learning technologies and individual cerebral spontaneous activity patterns to predict acupuncture treatment outcomes in patients with MWoA. The data provided a quantitative benchmark for selecting acupuncture for MWoA.

A systematic review and meta-analysis of the efficacy and safety of arbidol in the treatment of coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is highly contagious, and the epidemic has spread to hundreds of countries around the world, and seriously threatens the life safety of people around the world. Arbidol is an antiviral drug with high potential against COVID-19, but evidence of effectiveness and safety is lacking. The systematic review protocol aims to formulate a research plan that can evaluate the efficacy and safety of arbidol for COVID-19. METHODS: The retrieval time will be from the database establishment to June 2020. The retrieval database will include the Cochrane Library, PubMed, Embase, OVID, CNKI, Wanfang, VIP, CBM, etc. The primary outcome will be clinical efficacy, and the secondary results will be accompanying symptoms, time for the temperature to return to normal, time of novel coronavirus nucleic acid turning negative, blood sample test, Computed Tomography examination, length of hospitalization, adverse reactions, and adverse events. RevManV.5.3 software will be used for meta-analysis, and fixed effects model, random-effects model, subgroup analysis, and descriptive analysis will be adopted according to the heterogeneity of the research results. RESULTS: To provide the latest evidence of clinical efficacy and safety of arbidol in the treatment of COVID-19. CONCLUSION: Our study will provide the latest evidence analysis of the efficacy and safety of arbidol for COVID-19, to provide evidence-based medicine for the prevention and control of this epidemic. REGISTRATION DETAILS: PROSPERO CRD42020189203.

A systematic review and meta-analysis of the efficacy and safety of western medicine routine treatment combined with Chinese herbal medicine in the treatment of COVID-19.

BACKGROUND: COVID-19 is a global public health emergency. At present, there is no highly effective medicine for the prevention and treatment of 2019-nCoV. Western medicine for COVID-19 is mainly based on symptomatic support therapy. Chinese herbal medicine has been used to prevent infectious diseases for thousands of years in China. Western medicine routine treatment combined with Chinese herbal medicine is an alternative clinical option but lacks evidence-based medical evidence. The systematic review protocol aims to formulate a research plan that can evaluate the efficacy and safety of western medicine routine treatment combined with Chinese herbal medicine for COVID-19. METHODS: We will search the following eight databases: Cochrane Library, PubMed, Embase, Medline, CNKI, Wanfang, VIP, and CBM. The search time is up to the end of July 2020. Two authors will independently complete literature screening, data extraction, and risk of bias assessment. In case of disagreement, the third author will assist in the judgment. The primary outcome will be the clinical cure rate. The secondary outcome will be accounting symptoms, fever time, time of virus nucleic acid turning negative, check the condition by drawing blood, pneumonia absorption rate, patient hospitalization time, severe conversion rate and case fatality rate, adverse reactions, and adverse events. Revman 5.3 will be used for systematic reviews and meta-analysis. The report of the protocol will follow the PRISMA-P statement, and the report of the systematic review and meta-analysis will follow the PRISMA statement. RESULTS: We will provide evidence-based medical evidence of the efficacy and safety of western medicine routine treatment combined with Chinese herbal medicine for COVID-19. The findings will be published in peer-reviewed journals. REGISTRATION DETAILS: CRD42020190106.

The catalytic activity for ginkgolic acid biodegradation, homology modeling and molecular dynamic simulation of salicylic acid decarboxylase.

The toxic ginkgolic acids are the main safety concern for the application of Ginkgo biloba. In this study, the degradation ability of salicylic acid decarboxylase (SDC) for ginkgolic acids was examined using ginkgolic acid C15:1 as a substrate. The results indicated that the content of ginkgolic acid C15:1 in Ginkgo biloba seeds was significantly decreased after 5 h treatment with SDC at 40 °Cand pH 5.5. In order to explore the structure of SDC and the interaction between SDC and substrates, homology modeling, molecular docking and molecular dynamics were performed. The results showed that SDC might also have a catalytic active center containing a Zn2+. Compared with the template structure of 2,6-dihydroxybenzoate decarboxylase, the residues surrounding the binding pocket, His10, Phe23 and Phe290, were replaced by Ala10, Tyr27 and Tyr301 in the homology constructed structure of SDC, respectively. These differences may significantly affect the substrates adaptability of SDC for salicylic acid derivatives.

DFT investigation on the decarboxylation mechanism of ortho hydroxy benzoic acids with acid catalysis.

A density functional theory (DFT) study was performed to explore the mechanisms of the acid-catalyzed decarboxylation reaction of salicylic acids using the B3LYP method with 6-31++G(d,p) basis set in both gas phase and aqueous environment. The α-protonated cation of carboxylate acid was formed during the decarboxylation process in acidic conditions, and the presence of hydrogen ions promotes decarboxylation greatly by significantly decreasing the overall reaction energy barriers to 20.98 kcal mol(-1) in gas phase and 20.93 kcal mol(-1) in water, respectively. The hydrogen in the α-carbon came directly from the acid rather than from the carboxyl group in neutral state. Compared with the reaction in gas phase, water in aqueous state causes the reaction to occur more easily. Substituents of methyl group, chlorine and fluorine at the ortho-position to the carboxyl of salicylic acid could further lower the decarboxylation energy barriers and facilitate the reaction.

Expression of CD40 in ovarian cancer and adenovirus-mediated CD40 ligand therapy on ovarian cancer in vitro.

AIMS AND BACKGROUND: To test the expression level of CD40 on ovarian cancer tissues and its correlation to clinicopathological features of patients and to evaluate the therapeutic effectiveness of adenovirus-mediated CD40 ligand on ovarian cancer in vitro. MATERIAL AND METHODS: The expression of CD40 on paraffin-embedded ovarian cancer tissues (n=58) and normal ovarian tissues (n=15) was tested by immunohistochemistry, and CD40 expression on ovarian cancer cells derived from fresh surgical specimens was tested by flow cytometry analysis. The apoptosis-inducing effects of adenovirus-mediated CD40 ligand therapy on ovarian cancer cells derived from fresh surgical specimens were analyzed by flow cytometry analysis and TUNEL assay. RESULTS: CD40 expression was detected in 60.3% (35/58) of paraffin-embedded ovarian cancer tissues and 73.3% (11/15) of fresh ovarian cancer tissues, but not in normal ovarian tissues (n=15). CD40 expression was significantly correlated with FIGO stage of ovarian cancer. Adenovirus-mediated CD40 ligand therapy induced significant apoptosis effects on ovarian cancer cells derived from fresh surgical specimens in vitro compared to null adenovirus vector and phosphate-buffered saline. CONCLUSIONS: Our results suggested the therapeutic potential of adenovirus-mediated CD40 ligand on ovarian cancer, especially on the late stage of ovarian cancer.