Efficacy of acupuncture combined with traditional Chinese herbal for primary epilepsy patients with cognitive impairment: A protocol for systematic review and meta-analysis.

BACKGROUND: Epilepsy is a common and serious chronic neurological disorder, and some patients suffer from cognitive dysfunction. We aim to assess the efficacy and safety of acupuncture combined with traditional Chinese herbal for primary epilepsy patients with cognitive impairment. METHODS: To search the randomized control trials (RCTs) published before April 20, 2023 from PubMed, Embase, Cochrane Library, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Web of science, and Wanfang Database. The risk of bias within each individual trial was evaluated using the Cochrane Collaboration tool. RevMan5.3 software was used for statistical analysis. The odds ratio (OR) or weighted mean difference (WMD) with a 95% confidence interval (CI) was calculated for each RCT before data pooling. RESULTS: The primary outcomes involve changes in cognitive function and behavioral disturbances. The secondary outcomes focused on quality of life and adverse effects. CONCLUSION: The results of this review are expected to provide new guidelines for the treatment of primary epilepsy patients with cognitive impairment. TRIAL REGISTRATION: This systematic review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) (Registration number: CRD42023415355).

The efficacy of acupuncture for trigeminal neuralgia: an overview of systematic reviews.

Background: Many systematic reviews (SRs) and meta-analysis (MAs) have reported the efficacy of acupuncture treatment for primary trigeminal neuralgia (PTN), but the quality of evidence is unknown and therefore needs to be evaluated comprehensively. Methods: Eight electronic databases were searched from their inception until January 5, 2024. The methodological quality, reporting quality, and risk of bias of the included SRs were assessed by the assessment of multiple systematic reviews 2 (AMSTAR-2), the Risk of Bias in Systematic Reviews (ROBIS) tool, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The quality of evidence for outcome measures was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: We identified 13 SRs/MAs met inclusion criteria. According to the results of the AMSTAR-2, six were rated as critically low quality and seven as low quality. According to ROBIS assessment, 8 SRs/MAs were classified as low risk, and 5 SRs/MAs were found to be high risk. The PRISMA report still has some reporting deficiencies in aspects such as protocol and registration, search strategy, risk of bias, additional analyzes and funding. According to the GRADE system, no high-quality evidence was found, 1 was of moderate quality, 4 were of low quality, and 8 were of critical low quality. Conclusion: Based on the evidence collected, acupuncture shows promise as a treatment for PTN patients. However, it is important to note that the included SRs/MAs generally have low methodological quality and evidence quality. Therefore, caution must be exercised when interpreting this conclusion. To enhance future research in this area, it is recommended to adequately report methodological details and adhere to guidelines for conducting SRs/MAs.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024499280.

Repetitive transcranial magnetic stimulation for Alzheimer's disease: an overview of systematic reviews and meta-analysis.

Objective: Alzheimer's disease (AD) is a prevalent neurodegenerative condition that significantly impacts both individuals and society. This study aims to evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) as a treatment for AD by summarizing the evidence from systematic reviews (SRs) and meta-analyses (MAs). Methods: SRs/MAs of rTMS for AD were collected by searching Embase, Web of Science, Cochrane Library, PubMed, CNKI, VIP, Sino-Med, and Wanfang databases. The search was conducted from database creation to January 23, 2024. Methodological quality, reporting quality and risk of bias were assessed using the Assessing Methodological Quality of Systematic Reviews 2 (AMSTAR-2), Risk of Bias in Systematic Reviews (ROBIS) tool and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). In addition, the quality of evidence for outcome measures was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Results: Eight SRs/MAs included in this study met the inclusion criteria. Based on the AMSTAR-2, 4 of the SRs/MA were classified as low quality, while the remaining 4 were deemed to be of very low quality. The PRISMA analysis revealed that out of the 27 items reporting, 16 achieved full reporting (100%). However, there were still some deficiencies in reporting, particularly related to protocol and registration, search strategy, risk of bias, and additional analysis. The ROBIS tool indicated that only 3 SRs/MAs had a low risk of bias. The GRADE assessment indicated that 6 outcomes were of moderate quality (18.75%), 16 were of low quality (50%), and 10 were classified as very low quality (31.25%). Conclusion: Based on the evidence collected, rTMS appears to be effective in improving cognitive function in AD patients, although the methodological quality of the SRs/MAs reduces the reliability of the conclusions and the overall quality is low. However, based on the available results, we still support the value of rTMS as an intervention to improve cognitive function in AD. In future studies, it is necessary to confirm the efficacy of rTMS in AD patients and provide more reliable and scientific data to contribute to evidence-based medicine.

Effects of acupuncture treatment for myasthenia gravis: A systematic review and meta-analysis.

BACKGROUND: Randomized controlled trials (RCTs) of acupuncture for myasthenia gravis (MG) were searched and the efficacy of acupuncture in the treatment of MG was evaluated by meta-analysis. METHODS: We searched for RCTs in six main electronic databases, and collected RCTs of acupuncture treatment for MG from database creation to 28 February 2023. The main outcome was the effective rate and the secondary outcome was the Traditional Chinese Medicine (TCM) relative clinical score, absolute clinical score (ACS) of MG, Quantitive myasthenia gravis score (QMG), quality of life, and adverse events. Odds ratios (ORs) and weighted mean differences (WMD) and 95% confidence intervals (CI) were used to assess pooled effect estimates using Review Manager software. RESULTS: A total of 14 RCTs were included. Meta-analysis showed that the effective rate in the acupuncture group was significantly improved compared with conventional Western medicine alone [OR = 4.28, 95% CI (2.95, 6, 22), P<0.005]. The pooled WMDs revealed that TCM relative clinical score [WMD = -2.22, 95% CI = (-2.53, -1.90), P<0.005], ACS of MG [WMD = -3.14, 95% CI = (-3.67, -2.62), P<0.005], and QMG [WMD = -0.88, 95% CI = (-1.46, -0.29), P<0.005] in the acupuncture group was lower than the control group. Adverse reactions related to acupuncture and quality of life were less mentioned among included RCTs. CONCLUSION: This meta-analysis demonstrated that acupuncture as an auxiliary may play a positive role in treating MG. It can improve the effective rate of treatment, and reduce TCM relative clinical score, ACS of MG, and QMG. However, the quality of included studies was generally low and caution should be exercised when considering this treatment option. In the future, more rigorous study designs and high-quality RCTs are needed to verify the efficacy of acupuncture in the treatment of MG, because the results of high-quality RCTs are more reliable and accurate.

Autoimmune encephalitis in COVID-19 patients: a systematic review of case reports and case series.

Background: There is mounting evidence suggesting that autoimmune encephalitis (AE) can be observed as a neurological complication in patients with COVID-19. This review aimed to summarize the clinical manifestations, types, and outcomes of COVID-19-associated AE. Methods: A systematic search was conducted in the PubMed, Embase, and Web of Science databases to identify case reports and case series related to COVID-19-associated AE from 1 January 2020 to 31 March 2023. After a thorough screening and evaluation, irrelevant articles were excluded. Relevant information concerning types, clinical manifestations, and outcomes was extracted and synthesized. Results: A total of 37 studies, comprising 34 case reports and 3 case series, were included in this review. Among the 42 COVID-19-associated AE patients, 21 (50%) cases were classified as an unknown antibodies (Ab) type of COVID-19-associated AE, 10 (23.80%) cases as anti-N-methyl-D-aspartate (NMDA) encephalitis, 4 (9.5%) cases as limbic encephalitis, and 3 (7.1%) cases as anti-myelin-oligodendrocyte-glycoprotein encephalitis, along with other rare types of AE. Disturbance of consciousness, seizures, and psychiatric symptoms were identified as the main clinical manifestations of COVID-19-associated AE. While the symptoms of AE displayed variation, most patients achieved full recovery although a few experienced residual symptoms of neurological damage. Conclusion: This systematic review comprehensively describes the characteristics of COVID-19-associated AE. The main type of COVID-19-associated AE identified in this study is an unknown Ab type of COVID-19-associated AE. Despite the potentially life-threatening risks of COVID-19-associated AE, the majority of patients survived, with some patients reporting residual neurological symptoms.

Effectiveness of acupuncture as auxiliary combined with Western medicine for epilepsy: a systematic review and meta-analysis.

Background: Although more and more clinical studies have shown that acupuncture as an auxiliary combined with Western medicine is effective in the treatment of patients with epilepsy, no systematic reviews of acupuncture as a treatment for epilepsy have been published. Hence, we conducted this meta-analysis to evaluate the effect of acupuncture treatment on patients with epilepsy. Methods: This study retrieved randomized controlled trials (RCTs) of acupuncture treatment for epilepsy from various electronic databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese BioMedical Literature Database, and Wangfang database. These studies evaluated the effectiveness of acupuncture as an auxiliary treatment combined with Western medicine for patients with epilepsy. The methodological quality of the studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. Results: A total of 17 RCTs involving a total of 1,389 participants were included. The results showed that acupuncture combined with Western medicine improved the effective rates of treatment (OR: 4.28; 95% CI: 3.04-6.02; p < 0.001), and reduced the seizure frequency of patients (SMD: -3.29; 95% CI: -3.51 to -3.07; p < 0.001) and the EEG discharge frequency (SMD: -5.58; 95% CI: -7.02 to -4.14; p < 0.001). Regarding the quality of life and adverse events, the acupuncture group was superior to the control group in improving the overall quality of life of patients with epilepsy (SMD: 14.41; 95% CI: 12.51-16.32; p < 0.001) and decreased adverse events (OR: 0.38; 95% CI: 0.23-0.63, p < 0.001). Conclusion: The results of the analysis suggested that acupuncture combined with Western medicine is probably helpful in patients with epilepsy, but strong supportive data are not yet available. Given that this study is based on a low to moderate evidence-based analysis, the conclusions should be viewed with caution. Systematic review registration: PROSPERO, identifier no. CRD42023409923.

Anti-Proliferation and Pro-Apoptotic Effects of Diosmetin via Modulating Cell Cycle Arrest and Mitochondria-Mediated Intrinsic Apoptotic Pathway in MDA-MB-231 Cells.

BACKGROUND Breast cancer is one of the most malignant tumors worldwide. The natural flavonoid diosmetin has been reported to exhibit various pharmacological activities, including anti-cancer effects. This study aimed to investigate the anti-breast cancer effects of diosmetin on MDA-MB-231 cells and to explore the underlying molecular mechanisms of cell apoptosis. MATERIAL AND METHODS The MDA-MB-231 cells were incubated with diosmetin for 24 h. Then, cell viability and lactate dehydrogenase (LDH) leakage were detected using CCK-8 and LDH assay kits, respectively. Inverted fluorescence microscopy and flow cytometry were used to measure the mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS). Cell apoptosis and cell cycle were determined by flow cytometry. The expressions of apoptosis and cell cycle-related genes were determined by Western blotting and qRT-PCR. RESULTS The results revealed that diosmetin exerts significant cytotoxic effects on MDA-MB-231 cells, as indicated by decreased cell viability, increased intracellular ROS accumulation and LDH release, as well as cell cycle arrest in G0/G1 phase, inducing mitochondrial dysfunction and apoptosis. Moreover, diosmetin treatment significantly downregulated the expression levels of Bcl-2 and Cyclin D1, and upregulated that of p53, Bax, caspase 3, cleaved caspase 9, and cleaved caspase 3. CONCLUSIONS These findings demonstrate that diosmetin has anti-proliferative and pro-apoptotic activities against MDA-MB-231 cells via cell cycle arrest and the mitochondria-mediated intrinsic apoptotic pathway. Our results extend the understanding of the anti-tumor mechanism of diosmetin and suggest that it may be of use as an active natural agent for the prevention or treatment of human breast cancer.

Snf1 is a regulator of lipid accumulation in Yarrowia lipolytica.

In the oleaginous yeast Yarrowia lipolytica, de novo lipid synthesis and accumulation are induced under conditions of nitrogen limitation (or a high carbon-to-nitrogen ratio). The regulatory pathway responsible for this induction has not been identified. Here we report that the SNF1 pathway plays a key role in the transition from the growth phase to the oleaginous phase in Y. lipolytica. Strains with a Y. lipolytica snf1 (Ylsnf1) deletion accumulated fatty acids constitutively at levels up to 2.6-fold higher than those of the wild type. When introduced into a Y. lipolytica strain engineered to produce omega-3 eicosapentaenoic acid (EPA), Ylsnf1 deletion led to a 52% increase in EPA titers (7.6% of dry cell weight) over the control. Other components of the Y. lipolytica SNF1 pathway were also identified, and their function in limiting fatty acid accumulation is suggested by gene deletion analyses. Deletion of the gene encoding YlSnf4, YlGal83, or YlSak1 significantly increased lipid accumulation in both growth and oleaginous phases compared to the wild type. Furthermore, microarray and quantitative reverse transcription-PCR (qRT-PCR) analyses of the Ylsnf1 mutant identified significantly differentially expressed genes during de novo lipid synthesis and accumulation in Y. lipolytica. Gene ontology analysis found that these genes were highly enriched with genes involved in lipid metabolism. This work presents a new role for Snf1/AMP-activated protein kinase (AMPK) pathways in lipid accumulation in this oleaginous yeast.

Identification and characterization of new Δ-17 fatty acid desaturases.

ω-3 fatty acid desaturase is a key enzyme for the biosynthesis of ω-3 polyunsaturated fatty acids via the oxidative desaturase/elongase pathways. Here we report the identification of three ω-3 desaturases from oomycetes, Pythium aphanidermatum, Phytophthora sojae, and Phytophthora ramorum. These new ω-3 desaturases share 55 % identity at the amino acid level with the known Δ-17 desaturase of Saprolegnia diclina, and about 31 % identity with the bifunctional Δ-12/Δ-15 desaturase of Fusarium monoliforme. The three enzymes were expressed in either wild-type or codon optimized form in an engineered arachidonic acid producing strain of Yarrowia lipolytica to study their activity and substrate specificity. All three were able to convert the ω-6 arachidonic acid to the ω-3 eicosapentanoic acid, with a substrate conversion efficiency of 54-65 %. These enzymes have a broad ω-6 fatty acid substrate spectrum, including both C18 and C20 ω-6 fatty acids although they prefer the C20 substrates, and have strong Δ-17 desaturase activity but weaker Δ-15 desaturase activity. Thus, they belong to the Δ-17 desaturase class. Unlike the previously identified bifunctional Δ-12/Δ-15 desaturase from F. monoliforme, they lack Δ-12 desaturase activity. The newly identified Δ-17 desaturases could use fatty acids in both acyl-CoA and phospholipid fraction as substrates. The identification of these Δ-17 desaturases provides a set of powerful new tools for genetic engineering of microbes and plants to produce ω-3 fatty acids, such as eicosapentanoic acid and docosahexanoic acid, at high levels.

Isolation of a Δ5 desaturase gene from Euglena gracilis and functional dissection of its HPGG and HDASH motifs.

Delta (Δ) 5 desaturase is a key enzyme for the biosynthesis of health-beneficial long chain polyunsaturated fatty acids such as arachidonic acid (ARA, C20:4n-6), eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3) via the "desaturation and elongation" pathways. A full length Δ5 desaturase gene from Euglena gracilis (EgΔ5D) was isolated by cloning the products of polymerase chain reaction with degenerate oligonucleotides as primers, followed by 5' and 3' rapid amplification of cDNA ends. The whole coding region of EgΔ5D was 1,350 nucleotides in length and encoded a polypeptide of 449 amino acids. BlastP search showed that EgΔ5D has about 39 % identity with a Δ5 desaturase of Phaeodactylum tricornutum. In a genetically modified dihomo-gamma-linoleic acid (DGLA, C20:3n-6) producing Yarrowia lipolytica strain, EgΔ5D had strong Δ5 desaturase activity with DGLA to ARA conversion of more than 24 %. Functional dissection of its HPGG and HDASH motifs demonstrated that both motifs were important, but not necessary in the exact form as encoded for the enzyme activity of EgΔ5D. A double mutant EgΔ5D-34G158G with altered sequences within both HPGG and HDASH motifs was generated and exhibited Δ5 desaturase activity similar to the wild type EgΔ5D. Codon optimization of the N-terminal region of EgΔ5D-34G158G and substitution of the arginine with serine at residue 347 improved substrate conversion to 27.6 %.

Mutational and functional analysis of the beta-carotene ketolase involved in the production of canthaxanthin and astaxanthin.

Biosynthesis of the commercial carotenoids canthaxanthin and astaxanthin requires beta-carotene ketolase. The functional importance of the conserved amino acid residues of this enzyme from Paracoccus sp. strain N81106 (formerly classified as Agrobacterium aurantiacum) was analyzed by alanine-scanning mutagenesis. Mutations in the three highly conserved histidine motifs involved in iron coordination abolished its ability to catalyze the formation of ketocarotenoids. This supports the hypothesis that the CrtW ketolase belongs to the family of iron-dependent integral membrane proteins. Most of the mutations generated at other highly conserved residues resulted in partial activity. All partially active mutants showed a higher amount of adonixanthin accumulation than did the wild type when expressed in Escherichia coli cells harboring the zeaxanthin biosynthetic gene cluster. Some of the partially active mutants also produced a significant amount of echinenone when expressed in cells producing beta-carotene. In fact, expression of a mutant carrying D117A resulted in the accumulation of echinenone as the predominant carotenoid. These observations indicate that partial inactivation of the CrtW ketolase can often lead to the production of monoketolated intermediates. In order to improve the conversion rate of astaxanthin catalyzed by the CrtW ketolase, a color screening system was developed. Three randomly generated mutants, carrying L175M, M99V, and M99I, were identified to have improved activity. These mutants are potentially useful in pathway engineering for the production of astaxanthin.

Triage protein fold prediction.

We have constructed, in a completely automated fashion, a new structure template library for threading that represents 358 distinct SCOP folds where each model is mathematically represented as a Hidden Markov model (HMM). Because the large number of models in the library can potentially dilute the prediction measure, a new triage method for fold prediction is employed. In the first step of the triage method, the most probable structural class is predicted using a set of manually constructed, high-level, generalized structural HMMs that represent seven general protein structural classes: all-alpha, all-beta, alpha/beta, alpha+beta, irregular small metal-binding, transmembrane beta-barrel, and transmembrane alpha-helical. In the second step, only those fold models belonging to the determined structural class are selected for the final fold prediction. This triage method gave more predictions as well as more correct predictions compared with a simple prediction method that lacks the initial classification step. Two different schemes of assigning Bayesian model priors are presented and discussed.