Research hotspots and frontiers of cluster headaches: a bibliometric analysis.

Background: Extensive research on cluster headaches (CHs) has been conducted worldwide; however, there is currently no bibliometric research on CHs. Therefore, this study aimed to analyze the current research hotspots and frontiers of CHs over the past decade. Methods: Raw data on CHs was obtained from the Web of Science Core Collection database from 2014 to 2023. CiteSpace V6.2 R7 (64 bit) and Microsoft Excel were used to assess the annual publication volume, authors, countries, and references. VOSviewer 1.6.19 software was used to assess the institutions, cited authors, and keywords, and co-occurrence and clustering functions were applied to draw a visual knowledge map. Results: In the past decade, the overall annual publication volume of articles related to CHs has increased year by year, showing promising development prospects. The total 1909 articles contained six types of literature, among which the proportion of original research articles was the highest (1,270 articles, 66.53%), published in 201 journals. Cephalalgia (439 articles, 23.00%) had the highest publication volume, and the Lancet was the journal with the highest impact factor (IF = 168.9). Furthermore, the United States of America was the country with the most published papers (584 articles, 30.60%), University of London was the research institution with the most published papers (142 articles, 7.44%), and Goodsby, Peter J was found to be the most prolific author (38 articles, 1.99%). Conclusion: This study may provide some direction for subsequent researcher on CHs. The hotspots and frontiers of future research on CHs are suggested as follows: in basic medicine, more attention should be paid to pathophysiology, especially on increasing research on the pathogenesis mediated by CGRP; in clinical medicine, more attention should be paid to the design of evidence-based medicine methodology, especially the strict design, including double-blind, questionnaire, and follow-up, in randomized controlled trials, using high-quality articles for meta-analyses, and recommending high-level evidence; therapeutic techniques need to be further explored, suggesting the implementation of transcranial magnetic stimulation of the cortex, and stimulation of the sphinopalatine ganglia and occipital nerve to achieve peripheral neuromodulation. Furthermore, chronic migraine and insomnia are inextricably linked to CHs.

A Bibliometric Analysis of Acupuncture Therapy in the Treatment of Musculoskeletal Pain from 2003 to 2022.

Background: Acupuncture therapy has been widely used in the treatment of musculoskeletal pain (MP) in many countries around the world. However, there are no bibliometric studies on acupuncture therapy for MP. Therefore, the aim of this study was to analyze the current status, frontiers and hot spots in the use of acupuncture therapy for the treatment of MP. Methods: Literature on acupuncture therapy for MP was extracted from the Web of Science Core Collection database from 2003 to 2022. CiteSpace 6.2.R4 (64-bit) software was used to analyze the number and centrality of journals, countries, institutions, authors, references and keywords, and the functions of co-occurrence and clustering were applied to draw a visual knowledge map. Results: Over the past 20 years, the annual journal publications have been on a steady upward trend, with 438 articles published in 143 journals, including Acupuncture in Medicine Journal published the most (28, 6.39%), JAMA-Journal of the American Medical Association was the journal with the highest impact factor (IF = 120.7003), USA dominated with the most publications (140, 31.96%) among 44 countries, and among 196 research organizations Kyung Hee University was the most prolific (19, 4.34%) and Ha, In-Hyuk was the most published author (9, 2.05%). "Acupuncture" is the most popular and highly sought after keywords. "Low back pain" is the keyword with the highest centrality. Conclusion: This article provides the current situation of the use of acupuncture therapy in the treatment of MP in the past 20 years, and statistical analysis reveals that "low back pain", "knit osteoporosis" and "break cancer" are new research diseases related to acupuncture therapy for MP, and "myobasic trigger point" is a new research direction of acupuncture therapy for MP. Therefore, this study helps researchers grasp the research hotspots and provide certain references for in-depth research and future topic selection.

Association of urinary phthalate metabolites with all-cause and cardiovascular disease mortality among adults with diabetes mellitus: National Health and Nutrition Examination Survey 2005-2014.

Background: The study regarding phthalate metabolites and mortality among diabetes mellitus (DM) is limited. We aimed to examine the association of urinary phthalate metabolites with all-cause and cardiovascular disease (CVD) mortality among adults with DM. Methods: This study included 8,931 adults from the National Health and Nutrition Examination Survey (NHANES) from 2005-2006 to 2013-2014. Mortality data were linked to National Death Index public access files through December 31, 2015. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidences (CIs) for mortality. Results: We identified 1,603 adults with DM [mean ± SE age, 47.08 ± 0.30 years; 50.5% (833) were men]. Mono-(carboxynonyl) phthalate (MCNP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), and the sum of Di (2-ethylhexyl) phthalate (DEHP) metabolites (∑DEHP) were positively associated with DM (MCNP: OR = 1.53, 95%CI = 1.16-2.01; MECPP: OR = 1.17, 95% CI = 1.03-1.32; ∑DEHP: OR = 1.14, 95% CI = 1.00-1.29). Among DM patients, mono-(3-carboxypropyl) phthalate (MCPP) was associated with a 34% (HR 1.34, 95% CI 1.12-1.61) increased risk of all-cause mortality while the HRs (95%CI) of CVD mortality were 2.02 (1.13-3.64) for MCPP, 2.17 (1.26-3.75) for mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), 2.47 (1.43-4.28) for mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), 2.65 (1.51-4.63) for MECPP, and 2.56 (1.46-4.46) for ∑DEHP, respectively. Conclusion: This study is an academic exploration of the association between urinary phthalate metabolites and mortality among adults with DM, suggesting that exposure to phthalates might be associated with an increased risk of all-cause and CVD mortality in DM. These findings suggest that patients with DM should carefully use plastics products.

Mitochondrial-Targeted Antioxidant MitoQ-Mediated Autophagy: A Novel Strategy for Precise Radiation Protection.

Radiotherapy (RT) is one of the most effective cancer treatments. However, successful radiation protection for normal tissue is a clinical challenge. Our previous study observed that MitoQ, a mitochondria-targeted antioxidant, was adsorbed to the inner mitochondrial membrane and remained the cationic moiety in the intermembrane space. The positive charges in MitoQ restrained the activity of respiratory chain complexes and decreased proton production. Therefore, a pseudo-mitochondrial membrane potential (PMMP) was developed via maintenance of exogenous positive charges. This study identified that PMMP constructed by MitoQ could effectively inhibit mitochondrial respiration within normal cells, disrupt energy metabolism, and activate adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling to induce autophagy. As such, it could not lead to starvation-induced autophagy among tumor cells due to the different energy phenotypes between normal and tumor cells (normal cells depend on mitochondrial respiration for energy supply, while tumor cells rely on aerobic glycolysis). Therefore, we successfully protected the normal cells from radiation-induced damage without affecting the tumor-killing efficacy of radiation by utilizing selective autophagy. MitoQ-constructed PMMP provides a new therapeutic strategy for specific radiation protection.

The roles of divergent and parallel molecular evolution contributing to thermal adaptive strategies in trees.

Local adaptation is a driver of biological diversity, and species may develop analogous (parallel evolution) or alternative (divergent evolution) solutions to similar ecological challenges. We expect these adaptive solutions would culminate in both phenotypic and genotypic signals. Using two Eucalyptus species (Eucalyptus grandis and Eucalyptus tereticornis) with overlapping distributions grown under contrasting 'local' temperature conditions to investigate the independent contribution of adaptation and plasticity at molecular, physiological and morphological levels. The link between gene expression and traits markedly differed between species. Divergent evolution was the dominant pattern driving adaptation (91% of all significant genes); but overlapping gene (homologous) responses were dependent on the determining factor (plastic, adaptive or genotype by environment interaction). Ninety-eight percent of the plastic homologs were similarly regulated, while 50% of the adaptive homologs and 100% of the interaction homologs were antagonistical. Parallel evolution for the adaptive effect in homologous genes was greater than expected but not in favour of divergent evolution. Heat shock proteins for E. grandis were almost entirely driven by adaptation, and plasticity in E. tereticornis. These results suggest divergent molecular evolutionary solutions dominated the adaptive mechanisms among species, even in similar ecological circumstances. Suggesting that tree species with overlapping distributions are unlikely to equally persist in the future.

Limited hydraulic recovery in seedlings of six tree species with contrasting leaf habits in subtropical China.

Subtropical tree species may experience severe drought stress due to variable rainfall under future climates. However, the capacity to restore hydraulic function post-drought might differ among co-occurring species with contrasting leaf habits (e.g., evergreen and deciduous) and have implications for future forest composition. Moreover, the links between hydraulic recovery and physiological and morphological traits related to water-carbon availability are still not well understood. Here, potted seedlings of six tree species (four evergreen and two deciduous) were grown outdoors under a rainout shelter. They grew under favorable water conditions until they were experimentally subjected to a soil water deficit leading to losses of ca. 50% of hydraulic conductivity, and then soils were re-watered to field capacity. Traits related to carbon and water relations were measured. There were differences in drought responses and recovery between species, but not as a function of evergreen or deciduous groups. Sapindus mukorossi exhibited the most rapid drought response, which was associated with a suite of physiological and morphological traits (larger plant size, the lowest hydraulic capacitance (C branch), higher minimum conductance (g min) and lower HV (Huber value)). Upon re-watering, xylem water potential exhibited fast recovery in 1-3 days among species, while photosynthesis at saturating light (A sat) and stomatal conductance (g s) recovery lagged behind water potential recovery depending on species, with g s recovery being more delayed than A sat in most species. Furthermore, none of the six species exhibited significant hydraulic recovery during the 7 days re-watering period, indicating that xylem refilling was apparently limited; in addition, NSC availability had a minimal role in facilitating hydraulic recovery during this short-term period. Collectively, if water supply is limited by insignificant hydraulic recovery post-drought, the observed carbon assimilation recovery of seedlings may not be sustained over the longer term, potentially altering seedling regeneration and shifting forest species composition in subtropical China under climate change.

Effects of Concurrent Exposure to Chronic Restraint-Induced Stress and Total-Body Iron Ion Radiation on Induction of Kidney Injury in Mice.

Concurrent exposure to ionizing radiation (IR) and psychological stress (PS) may affect the development of adverse health consequences in scenarios such as space missions, radiotherapy and nuclear accidents. IR can induce DNA damage and cell apoptosis in the kidneys, thus potentially leading to renal fibrosis, which is the ultimate outcome of various chronic progressive nephropathies and the morphological manifestation of a continuous coordinated response after renal injury. However, little is known regarding the effects of concurrent IR exposure and PS on renal damage, particularly renal fibrosis. In this study, using a chronic restraint-induced PS (CRIPS) model, we exposed Trp53-heterozygous mice to total body irradiation with 0.1 or 2 Gy 56Fe ions on the eighth day of 28 consecutive days of a restraint regimen. At the end of the restraint period, the kidneys were collected. The histopathological changes and the degree of kidney fibrosis were assessed with H&E and Masson staining, respectively. Fibronectin (FN) and alpha smooth muscle actin (α-SMA), biomarkers of fibrosis, were detected by immunohistochemistry. Analysis of 8-hydroxy-2 deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, was performed with immunofluorescence, and terminal deoxynucleotidyl transferase-mediated nick end labeling assays were used to detect apoptotic cells. Histopathological observations did not indicate significant structural damage induced by IR or CRIPS + IR. Western blotting revealed that the expression of α-SMA was much higher in the CRIPS + IR groups than the CRIPS groups. However, no differences in the average optical density per area were observed for FN, α-SMA and 8-OHdG between the IR and CRIPS + IR groups. No difference in the induction of apoptosis was observed between the IR and CRIPS + IR groups. These results suggested that exposure to IR (0.1 and 2 Gy 56Fe ions), 28 consecutive days of CRIPS or both did not cause renal fibrosis. Thus, CRIPS did not alter the IR-induced effects on renal damage in Trp53-heterozygous mice in our experimental setup.

Variation of microbial activities and communities in petroleum-contaminated soils induced by the addition of organic materials and bacterivorous nematodes.

Bacterivorous nematodes are abundant in petroleum-contaminated soils. However, the ecological functions of bacterivorous nematodes and their impacts together with the addition of organic materials on the activity and diversity of microorganisms in petroleum-contaminated soils remain unknown. To assess such effects, six treatments were established in this study, including uncontaminated nematodes-free soil (Control), petroleum-contaminated soil (PC), petroleum-contaminated soil + 5 nematodes per gram dry soil (PCN), and petroleum-contaminated soil + 5 nematodes per gram dry soil + 1% wheat straw (PCNW), or + 1% rapeseed cake (PCNR), or + 1% biochar (PCNB). Results showed that the enzyme activities in the six treatments generally increased firstly and then decreased during the incubation period. Compared with Control, the invertase activity in PCNW, PCNR, and PCNB increased by 80.6%, 313.5%, and 12.4%, respectively, whereas the urease activity in PC, PCN, PCNW, PCNR, and PCNW increased by 1.2%, 25.5%, 124.3%, 105.3%, and 25.5%, respectively. Petroleum pollution, inoculation of bacterivorous nematodes, and the addition of organic materials all significantly boosted the concentrations of phospholipid fatty acids (PLFAs) of soil bacteria, actinobacteria, and total microorganisms, and increased the concentrations of both G+ and G- bacteria PLFAs and the ratio of G-/G+. The concentration of fungi PLFAs and the ratio of fungi to bacteria were significantly higher in PCNW and PCNR than those in other treatments. Overall, adding bacterivorous nematodes and organic materials to the petroleum-contaminated soil significantly improved soil microbial activity and community structure, suggesting that bacterivorous nematodes could be used for the bioremediation in petroleum contaminated soils.

Comparison of External Beam Radiation Therapy Modalities for Hepatocellular Carcinoma With Macrovascular Invasion: A Meta-Analysis and Systematic Review.

PURPOSE: We performed a systematic review and meta-analysis to compare external beam radiation therapy modalities for hepatocellular carcinoma (HCC) with macrovascular invasion (MVI). METHODS: Studies were selected from online databases from the date of inception to November 2021. The outcomes of interest were overall survival (OS), objective response rate (ORR), and local control rate (LCR). RESULTS: Forty-four studies (n = 3730) were selected from 1050 articles. The pooled 1-year OS were 60.9%, 45.3%, and 44.9 for particle radiotherapy (PRT) group, conventional radiotherapy (CRT), and stereotactic body radiotherapy (SBRT) group, respectively; p = 0.005 and 0.002 for PRT vs. CRT and SBRT, respectively. Both the PRT group and the SBRT group have the advantage over the CRT group in the pooled ORR. The PRT group showed significantly higher than the CRT group (p = 0.007) in LCR. For combination therapy, CRT plus transarterial chemoembolization can prolong survival than CRT alone (p = 0.006 for 1-year OS; p = 0.014 for 2-year OS). Among grade ≥ 3 complications, the most frequent type of toxicity in CRT, SBRT, PRT group was hematological toxicity, hepatotoxicity, dermatological toxicity, respectively. CONCLUSIONS: Among patients with HCC with MVI, the 1-year OS and the 2-year OS were both higher in the PRT group than in the CRT, SBRT groups. The ORR was similar between the PRT and SBRT groups. The combination therapy based on radiotherapy is expectable. PRT is associated with less complications than photon radiotherapy.

The reciprocal longitudinal relationship between body mass index and subjective well-being in China.

The relationship between body mass index (BMI) and subjective well-being (SWB) has been widely discussed in empirical literature. However, most previous studies were cross-sectional and inadequate to assess directionality. The current study examines the prospective relationship between BMI and SWB by analyzing nationally representative longitudinal data from 2009 to 2015. Eligible subjects were those who participated in a three-wave measurement (n = 18,443, age 13-99 years). We used a random-intercept cross-lagged panel model (RI-CLPM) to investigate the dynamic relationship between BMI and SWB, controlling for covariate effects. Results indicated that BMI and SWB were positively associated at the population level, and there was a reciprocal relationship at the individual level. An individual's BMI levels positively influenced his or her subsequent SWB values, with effects ranging from 0.15 (95% CI: 0.09-0.22) to 0.16 (95% CI: 0.09-0.24). At the same time, an individual's SWB levels positively influenced subsequent BMI values, with effects ranging from 0.12 (95% CI: 0.08-0.17) to 0.17 (95% CI: 0.10-0.24). This mutual reinforcement process supports the "jolly fat" hypothesis from a longitudinal perspective, implying that the psychosocial burden of excess weight may not hold in China. The implications are that mental health interventions could help prevent the risk of being underweight, and nutritional care would contribute to the creation of a happier society.

Loss of RPS27a expression regulates the cell cycle, apoptosis, and proliferation via the RPL11-MDM2-p53 pathway in lung adenocarcinoma cells.

BACKGROUND: Depletion of certain ribosomal proteins induces p53 activation, which is mediated mainly by ribosomal protein L5 (RPL5) and/or ribosomal protein L11 (RPL11). Therefore, RPL5 and RPL11 may link RPs and p53 activation. Thus, this study aimed to explore whether RPs interact with RPL11 and regulate p53 activation in lung adenocarcinoma (LUAD) cells. METHODS: The endogenous RPL11-binding proteins in A549 cells were pulled down through immunoprecipitation and identified with a proteomics approach. Docking analysis and GST-fusion protein assays were used to analyze the interaction of ribosomal protein S27a (RPS27a) and RPL11. Co-immunoprecipitation and in vitro ubiquitination assays were used to detect the effects of knockdown of RPS27a on the interaction between RPS27a and RPL11, and on p53 accumulation. Cell cycle, apoptosis, cell invasion and migration, cell viability and colony-formation assays were performed in the presence of knockdown of RPS27a. The RPS27a mRNA expression in LUAD was analyzed on the basis of the TCGA dataset, and RPS27a expression was detected through immunohistochemistry in LUAD samples. Finally, RPS27a and p53 expression was analyzed through immunohistochemistry in A549 cell xenografts with knockdown of RPS27a. RESULTS: RPS27a was identified as a novel RPL11 binding protein. GST pull-down assays revealed that RPS27a directly bound RPL11. Knockdown of RPS27a weakened the interaction between RPS27a and RPL11, but enhanced the binding of RPL11 and murine double minute 2 (MDM2), thereby inhibiting the ubiquitination and degradation of p53 by MDM2. Knockdown of RPS27a stabilized p53 in an RPL11-dependent manner and induced cell viability inhibition, cell cycle arrest and apoptosis in a p53-dependent manner in A549 cells. The expression of RPS27a was upregulated in LUAD and correlated with LUAD progression and poorer prognosis. Overexpression of RPS27a correlated with upregulation of p53, MDM2 and RPL11 in LUAD clinical specimens. Knockdown of RPS27a increased p53 activation, thus, suppressing the formation of A549 cell xenografts in nude mice. CONCLUSIONS: RPS27a interacts with RPL11, and RPS27a knockdown enhanced the binding of RPL11 and MDM2, thereby inhibiting MDM2-mediated p53 ubiquitination and degradation; in addition, RPS27a as important roles in LUAD progression and prognosis, and may be a therapeutic target for patients with LUAD.

Testing the limits of plant drought stress and subsequent recovery in four provenances of a widely distributed subtropical tree species.

Drought-induced tree mortality may increase with ongoing climate change. Unraveling the links between stem hydraulics and mortality thresholds, and the effects of intraspecific variation, remain important unresolved issues. We conducted a water manipulation experiment in a rain-out shelter, using four provenances of Schima superba originating from a gradient of annual precipitation (1124-1796 mm) and temperature (16.4-22.4°C). Seedlings were droughted to three levels of percentage loss of hydraulic conductivity (i.e., P50 , P88  and P99) and subsequently rewatered to field capacity for 30 days; traits related to water and carbon relations were measured. The lethal water potential associated with incipient mortality was between P50 and P88 . Seedlings exhibited similar drought responses in xylem water potential, hydraulic conductivity and gas exchange. Upon rehydration, patterns of gas exchange differed among provenances but were not related to the climate at the origin. The four provenances exhibited a similar degree of stem hydraulic recovery, which was correlated with the magnitude of antecedent drought and stem soluble sugar at the end of the drought. Results suggest that there were intraspecific differences in the capacity of S. superba seedlings for carbon assimilation during recovery, indicating a decoupling between gas exchange recovery and stem hydraulics across provenances.

Oil degradation and variation of microbial communities in contaminated soils induced by different bacterivorous nematodes species.

Oil pollution poses a great threat to environments and makes the remediation of oil-contaminated soils an urgent task. Microorganisms are the main biological factor for oil removal in the environment but microbial remediation is greatly affected by environmental factors. For our research, we inoculated three species of bacterivorous nematodes into oil-contaminated soil to explore how bacterivorous nematodes affect soil microbial activities and community structure in contaminated soil, as well as how efficiently different nematodes remove oil pollution from the soil. Six treatments were set in this experiment: sterilized oil-contaminated soil (SOC); nematode-free soil (S); oil-contaminated soil (OC); oil-contaminated soil + Caenorhabditis elegans (OCN1); oil-contaminated soil + Cephalobus persegnis (OCN2); oil-contaminated soil + Rhabditis marina (OCN3) for a 168-day incubation experiment. After the experiment was done, the oil contents in SOC, OC, OCN1, OCN2, and OCN3 were reduced by 6.5%, 32.3%, 38.2%, 42.8%, and 40.2%, respectively, compared with the beginning of the experiment. The amount of phospholipid fatty acids (PLFAs) of Gram-negative bacteria in OC, OCN1, OCN2, and OCN3 was increased by 50.9%, 43.4%, 37.7%, and 47.9%, respectively, compared with that of S. During the 168-day incubation period, the maximum growth of the number of nematodes in OCN1, OCN2, and OCN3 compared with the initial number of the nematodes were 2.25-, 1.52-, and 1.65-fold, respectively. The amount of oil residue in the contaminated soil negatively correlated with the populations of nematodes, total microorganisms, Gram-negative bacteria, actinomycetes, and eukaryotes. Thus, oil pollution increased the number of Gram-negative bacteria, decreased the ratio of Gram-positive bacteria/Gram-negative bacteria and Fungi/Bacteria significantly, and altered the community structure of soil microorganisms. Each species of bacterivorous nematodes has got its unique effect on the microbial activity and community structure in oil contaminated soils, but those tested can promote oil degradation and thus improve the environment of oil contaminated soils.

The crosstalk between HIFs and mitochondrial dysfunctions in cancer development.

Mitochondria are essential cellular organelles that are involved in regulating cellular energy, metabolism, survival, and proliferation. To some extent, cancer is a genetic and metabolic disease that is closely associated with mitochondrial dysfunction. Hypoxia-inducible factors (HIFs), which are major molecules that respond to hypoxia, play important roles in cancer development by participating in multiple processes, such as metabolism, proliferation, and angiogenesis. The Warburg phenomenon reflects a pseudo-hypoxic state that activates HIF-1α. In addition, a product of the Warburg effect, lactate, also induces HIF-1α. However, Warburg proposed that aerobic glycolysis occurs due to a defect in mitochondria. Moreover, both HIFs and mitochondrial dysfunction can lead to complex reprogramming of energy metabolism, including reduced mitochondrial oxidative metabolism, increased glucose uptake, and enhanced anaerobic glycolysis. Thus, there may be a connection between HIFs and mitochondrial dysfunction. In this review, we systematically discuss the crosstalk between HIFs and mitochondrial dysfunctions in cancer development. Above all, the stability and activity of HIFs are closely influenced by mitochondrial dysfunction related to tricarboxylic acid cycle, electron transport chain components, mitochondrial respiration, and mitochondrial-related proteins. Furthermore, activation of HIFs can lead to mitochondrial dysfunction by affecting multiple mitochondrial functions, including mitochondrial oxidative capacity, biogenesis, apoptosis, fission, and autophagy. In general, the regulation of tumorigenesis and development by HIFs and mitochondrial dysfunction are part of an extensive and cooperative network.

Crosstalk of the Caspase Family and Mammalian Target of Rapamycin Signaling.

Cell can integrate the caspase family and mammalian target of rapamycin (mTOR) signaling in response to cellular stress triggered by environment. It is necessary here to elucidate the direct response and interaction mechanism between the two signaling pathways in regulating cell survival and determining cell fate under cellular stress. Members of the caspase family are crucial regulators of inflammation, endoplasmic reticulum stress response and apoptosis. mTOR signaling is known to mediate cell growth, nutrition and metabolism. For instance, over-nutrition can cause the hyperactivation of mTOR signaling, which is associated with diabetes. Nutrition deprivation can inhibit mTOR signaling via SH3 domain-binding protein 4. It is striking that Ras GTPase-activating protein 1 is found to mediate cell survival in a caspase-dependent manner against increasing cellular stress, which describes a new model of apoptosis. The components of mTOR signaling-raptor can be cleaved by caspases to control cell growth. In addition, mTOR is identified to coordinate the defense process of the immune system by suppressing the vitality of caspase-1 or regulating other interferon regulatory factors. The present review discusses the roles of the caspase family or mTOR pathway against cellular stress and generalizes their interplay mechanism in cell fate determination.

Effects of ML351 and tissue plasminogen activator combination therapy in a rat model of focal embolic stroke.

Thrombolytic stroke therapy with tissue plasminogen activator (tPA) is limited by risks of hemorrhagic transformation (HT). We have reported that a new 12/15-lipoxygenase (12/15-LOX) inhibitor ML351 reduced tPA related HT in mice subjected to experimental stroke under anticoagulation. In this study, we asked whether ML351 can ameliorate tPA induced HT in an embolic stroke model. Rats were subjected to embolic middle cerebral artery occlusion with 2 or 3 hr ischemia and tPA infusion, with or without ML351. Regional cerebral blood flow was monitored 2 hr after ischemia and continuously monitored for 1 hr after treatment for determining reperfusion. Hemoglobin was determined in brain homogenates and infarct volume was quantified at 24 hr after stroke.12/15-LOX, cluster of differentiation 68(CD68), immunoglobulin G (IgG), and tight junction proteins expression was detected by immunohistochemistry. ML351 significantly reduced tPA related hemorrhage after stroke without affecting its thrombolytic efficacy. ML351 also reduced blood-brain barrier disruption and improved preservation of junction proteins. ML351 and tPA combination improved neurological deficit of rats even though ML351 did not further reduce the infarct volume compared to tPA alone treated animals. Pro-inflammatory cytokines were suppressed by ML351 both in vivo and in vitro experiments. We further showed that ML351 suppressed the expression of c-Jun-N-terminal kinase (JNK) in brains and microglia cultures, whereas exogenous 12-HETE attenuated this effect in vitro. In conclusion, ML351 and tPA combination therapy is beneficial in ameliorating HT after ischemic stroke. This protective effect is probably because of 12/15-LOX inhibition and suppression of JNK-mediated microglia/macrophage activation.

Abnormal Expression of Mitochondrial Ribosomal Proteins and Their Encoding Genes with Cell Apoptosis and Diseases.

Mammalian mitochondrial ribosomes translate 13 proteins encoded by mitochondrial genes, all of which play roles in the mitochondrial respiratory chain. After a long period of reconstruction, mitochondrial ribosomes are the most protein-rich ribosomes. Mitochondrial ribosomal proteins (MRPs) are encoded by nuclear genes, synthesized in the cytoplasm and then, transported to the mitochondria to be assembled into mitochondrial ribosomes. MRPs not only play a role in mitochondrial oxidative phosphorylation (OXPHOS). Moreover, they participate in the regulation of cell state as apoptosis inducing factors. Abnormal expressions of MRPs will lead to mitochondrial metabolism disorder, cell dysfunction, etc. Many researches have demonstrated the abnormal expression of MRPs in various tumors. This paper reviews the basic structure of mitochondrial ribosome, focuses on the structure and function of MRPs, and their relationships with cell apoptosis and diseases. It provides a reference for the study of the function of MRPs and the disease diagnosis and treatment.

Multilevel regulation and molecular mechanism of poly (rC)-binding protein 1 in cancer.

Poly (rC)-binding protein 1 (PCBP1), an RNA- or DNA-binding protein with a relative molecular weight of 38 kDa, which is characterized by downregulation in many cancer types. Numerous cases have indicated that PCBP1 could be considered as a tumor suppressor to inhibit tumorigenesis, development, and metastasis. In the current review, we described the multilevel regulatory roles of PCBP1, including gene transcription, alternative splicing, and translation of many cancer-related genes. Additionally, we also provided a brief overview about the inhibitory effect of PCBP1 on most common tumors. More importantly, we summarized the current research status about PCBP1 in hypoxic microenvironment, autophagy, apoptosis, and chemotherapy of cancer cells, aiming to clarify the molecular mechanisms of PCBP1 in cancer. Taken together, in-depth study of PCBP1 in cancer may provide new ideas for cancer therapy.

Effectiveness and safety of electroacupuncture for insomnia: A protocol for an overview of systematic reviews and meta-analysis.

BACKGROUND: Insomnia is a common disease characterized by difficulty falling and/or staying asleep, and accompanied by irritability or fatigue during wakefulness. It is widely reported that insomnia is one of the most extensive mental disorders which the incidence rate is estimated to be about 10%. Insomnia can have serious influences on patients health and quality of life. Electro acupuncture (EA) is reported to be efficacious and widely used for the treatment of insomnia in China. This overview aims to summarize the available evidence from current systematic reviews for the efficacy of electroacupuncture therapy for insomnia. METHODS: We will make a comprehensive retrieval in 7 databases as following:The time is limited from the construction of the library to August 2020. We will use the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool to evaluate methodological quality. Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA-P) will be used in the report checklist to assess the quality of reports in the study. The Grading of the Classification of Recommendations, Evaluation, Development and Evaluation (GRADE) will be used to evaluate the included SRs and meta-analysis. Our reviewers will conduct systematic reviews, qualification evaluation, data extraction, methodological quality and evidence quality screening in pairs. The outcomes of interest include: The Pittsburgh Sleep Quality Index (PSQI), The Insomnia Severity Index (ISI), Athens Insomnia Scale, Sleep parameters measured by either subjective or objective approaches, such as actigraphy, polysomnogram, and electroencephalogram. Or any other scale used to assess the level of illness. The evidence will be synthesized where appropriate based on patient subgroups and outcomes. RESULTS: The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: INPLASY202080087. CONCLUSION: This overview will provide comprehensive evidence of EA for patients with insomnia.