Exosomes are small extracellular vesicles 40–160 nm in diameter that are secreted by almost all cell types. Exosomes can carry diverse cargo including RNA, DNA, lipids, proteins, and metabolites. ...Exosomes transfer substances and information between cells by circulating in body fluids and are thus involved in diverse physiological and pathological processes in the human body. Recent studies have closely associated exosomal microRNAs (miRNAs) with various human diseases, including diabetes mellitus (DM), which is a complex multifactorial metabolic disorder disease. Exosomal miRNAs are emerging as pivotal regulators in the progression of DM, mainly in terms of pancreatic β‐cell injury and insulin resistance. Exosomal miRNAs are closely associated with DM‐associated complications, such as diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic cardiomyopathy (DCM), etc. Further investigations of the mechanisms of action of exosomal miRNAs and their role in DM will be valuable for the thorough understanding of the physiopathological process of DM. Here, we have summarized recent findings regarding exosomal miRNAs associated with DM to provide a new strategy for identifying potential diagnostic biomarkers and drug targets for the early diagnosis and treatment, respectively, of DM.
Recent studies have closely associated exosomal microRNAs (miRNAs) with various human diseases, including diabetes mellitus (DM), which is a complex multifactorial metabolic disorder disease. In the diabetic condition, exosomal miRNAs are taken up by recipient cells, where they exert their biological function and thereby modulate the progression of DM‐associated complications, including diabetic retinopathy (DR), diabetic macrovascular complications (DMCs), diabetic nephropathy (DN), diabetic foot ulcer (DFU), diabetic peripheral neuropathy (DPN), and diabetic cardiomyopathy (DCM).
Background
The global burden of gallbladder and biliary tract cancer (GBTC) is increasing. A comprehensive evaluation of the burden is crucial to improve strategies for GBTC prevention and treatment.
...Methods
The incidence rates, mortality, and disability‐adjusted life years (DALYs) of GBTC from 1990 to 2017 were extracted from the Global Burden of Diseases Study (GBD) 2017. Estimated annual percent changes (EAPCs) were calculated to quantify GBTC trends during the study period.
Results
Globally, there were 210,878 new cases, 173,974 deaths, and 3,483,046 DALYs because of GBTC in 2017. GBTC incidence increased by 76%, mortality increased by 65%, and DALYs increased by 52% from 1990 to 2017. In addition, relatively higher Socio‐Demographic Index regions had greater incidence and death rates but greatly decreased age‐standardized incidence rate (ASIR) and age‐standardized death rate (ASDR). At the national level, Chile had the highest ASIR (10.38 per 100,000 population) and the highest ASDR (10.43 per 100,000 population) in 2017. The largest increases in ASIR (EAPC, 3.38) and ASDR (EAPC, 3.39) were observed in Georgia. Nonlinear associations were observed between the ASDR, the Socio‐Demographic Index, and DALYs at the 21 GBD regional levels and at the national level. The proportions of GBTC age‐standardized deaths and DALYs attributable to high body mass index were 15.4% and 16%, respectively.
Conclusions
GBTC remains a major health burden worldwide. These findings are expected to prompt policymakers to establish a cost‐effective method for the early diagnosis, prevention, and treatment of GBTC, reducing its modifiable risk factors and reversing its increasing trends.
Lay Summary
Although the rates of age‐standardized incidence, death, and disability‐adjusted life‐years for gallbladder and biliary tract cancer decreased from 1990 to 2017, the numbers of these measures increased.
Nonlinear associations existed between the age‐standardized death rate, the Socio‐Demographic Index, and disability‐adjusted life‐years at the 21 regional and national levels in the Global Burden of Disease Study.
Gallbladder and biliary tract cancer (GBTC) remains a major health burden worldwide; however, the burden of GBTC varies geographically. Establishing a cost‐effective method for the early diagnosis, prevention, and treatment of GBTC, reducing its modifiable risk factors, and reversing the increasing trend are warranted to reduce the GBTC burden.
Pancreatitis is a critical public health problem, and the burden of pancreatitis is increasing. We report the rates and trends of the prevalence, incidence, and years lived with disability (YLDs) for ...pancreatitis at the global, regional, and national levels in 195 countries and territories from 1990 to 2017, stratified by sex, age, and sociodemographic index (SDI).
Data on pancreatitis were available from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Numbers and age-standardized prevalence, incidence, and YLDs' rates per 100,000 population were estimated through a systematic analysis of modeled data from the 2017 GBD study. Both acute and chronic pancreatitis are being modeled separately in the GBD 2017; however, our data show acute and chronic pancreatitis together. Estimates were reported with uncertainty intervals (UIs).
Globally, in 2017, the age-standardized rates were 76.2 (95% UIs 68.9 to 83.4), 20.6 (19.2 to 22.1), and 4.5 (2.3 to 7.6) per 100,000 population for the point prevalence, incidence, and YLDs, respectively. From 1990 to 2017, the percent changes in the age-standardized prevalence and YLDs rates increased, whereas the age-standardized incidence rate decreased. The global prevalence increased with age up to 60-64 years and 44-49 years in females and males, respectively, and then decreased, with no significant difference between females and males. The global prevalence rate increased with age, peaking in the 95+ age group, with no difference between sexes. Generally, positive correlation between age-standardized YLDs and SDIs at the regional and national levels was observed. Slovakia (297.7 273.4 to 325.3), Belgium (274.3 242.6 to 306.5), and Poland (266.7 248.2 to 284.4) had the highest age-standardized prevalence rates in 2017. Taiwan (Province of China) (104.2% 94.8 to 115.2%), Maldives (72.4% 66.5 to 79.2%), and Iceland (64.8% 57.2 to 72.9%) had the largest increases in age-standardized prevalence rates from 1990 to 2017.
Pancreatitis is a major public health issue worldwide. The age-standardized prevalence and YLDs rates increased, but the age-standardized incidence rate decreased from 1990 to 2017. Improving the quality of pancreatitis health data in all regions and countries is strongly recommended for better monitoring the burden of pancreatitis.
Appendicitis is the most common abdominal surgical emergency worldwide, and its burden has been changing. We report the level and trends of appendicitis prevalence, and incidence; and years lived ...with disability (YLD) in 204 countries and territories from 1990 to 2019, based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.
The numbers and age-standardized prevalence, incidence, and YLD rates per 100,000 population of appendicitis were estimated across regions and countries by age, sex, and sociodemographic index (SDI). All the estimates were reported with 95% uncertainty intervals (UIs).
Globally, the age-standardized prevalence and incidence rates of appendicitis in 2019 were 8.7 (95% UI 6.9 to 11.0) and 229.9 (95% UI 180.9 to 291.0) per 100,000 population, with increases of 20.8% (95% UI 18.9 to 23.0%) and 20.5% (95% UI 18.7 to 22.8%) from 1990 to 2019, respectively. Additionally, the age-standardized YLDs rate was 2.7 (95% UI 1.8 to 3.9) in 2019, with an increase of 20.4% (95% UI 16.2 to 25.1%) from 1990 to 2019. In 2019, the age-standardized prevalence, incidence, and YLD rates peaked in the 15-to-19-year age groups in both male and female individuals. However, no statistically significant differences were observed between the male and female individuals in all groups. Ethiopia, India, and Nigeria showed the largest increases in the age-standardized prevalence rate between 1990 and 2019. Generally, positive associations were found between the age-standardized YLD rates and SDI at the regional and national levels.
Appendicitis remains a major public health challenge globally. Increasing awareness of appendicitis and its risk factors and the importance of early diagnosis and treatment is warranted to reduce its the burden.
Background
Liver cancer is one of the most common cancers worldwide. We aimed to report the burden of liver cancer at the global, regional, and national levels in 204 countries from 1990 to 2019, ...stratified by etiology, sex, age, and sociodemographic index (SDI).
Methods
Data of mortality, incidence, and disability‐adjusted life years (DALYs) of liver cancer and its etiology were available from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2019. The trends in the liver cancer burden were assessed by the annual percentage change. All estimates are presented as numbers and age‐standardized rates (ASRs) per 100,000 population, with uncertainty intervals (UIs).
Results
Globally, 484,577 (95% UI 444,091–525,798) mortalities, 534,364 (486,550–588,639) incident cases, and 12,528,422 (11,400,671–13,687,675) disability‐adjusted life years (DALYs) due to liver cancer occurred in 2019. The ASRs were 5.95 (5.44–6.44), 6.51 (5.95–7.16), and 151.08 (137.53–164.8) per 100,000 population for the mortalities, incidences, and DALYs, respectively. From 1990 to 2019, the numbers increased, whereas the ASRs decreased. Hepatitis B and Hepatitis C are the major causes of liver cancer mortality. The liver cancer mortality in 2019 increased with age, peaking at 65–69 and 70–74 age group in males and females, respectively, and the number was higher in males than in females. Generally, there were nonlinear associations between the ASR and SDIs values at the regional and national levels. China had the highest numbers of mortalities, incident cases, and DALYs, whereas Mongolia has the highest ASR in 2019.
Conclusion
Liver cancer remains a major public health issue worldwide, but etiological and geographical variations exist. It is necessary to increase awareness of the population regarding liver cancer, its etiologies and the importance of early detection, and diagnosis and treatment.
Liver cancer is one of the most common cancers worldwide. We aim to report the burden of liver cancer at the global, regional, and national levels in 204 countries from 1990 to 2019, stratified by etiology, sex, age, and sociodemographic index (SDI). Liver cancer remains a major public health issue worldwide, but there are etiological and geographical variations. Increasing the awareness of the population regarding liver cancer, its etiologies and the importance of early detection, and diagnosis and treatment are needed.
Music plays an essential role in human life and can act as an expression to evoke human emotions. The diversity of music makes the listener's experience of music appear diverse. Different music can ...induce various emotions, and the same theme can also generate other feelings related to the listener's current psychological state. Music emotion recognition (MER) has recently attracted widespread attention in academics and industry. With the development of brain science, MER has been widely used in different fields, e.g., recommendation systems, automatic music composing, psychotherapy, and music visualization. Especially with the rapid development of artificial intelligence, deep learning-based music emotion recognition is gradually becoming mainstream. Besides, electroencephalography (EEG) enables external devices to sense neurophysiological signals in the brain without surgery. This non-invasive brain-computer signal has been used to explore emotions. This paper surveys EEG music emotional analysis, involving the analysis process focused on the music emotion analysis method, e.g., data processing, emotion model, and feature extraction. Then, challenging problems and development trends of EEG-based music emotion recognition is proposed. Finally, the whole paper is summarized.
Objective:
Prostate cancer (PCa) is an epithelial malignancy of the prostate that currently lacks effective treatment. Traditional Chinese medicine (TCM) can play an anticancer role through ...regulating the immune system, anti-tumor angiogenesis, regulating tumor cell apoptosis, autophagy dysfunction, and other mechanisms. This study attempted to explore the active ingredients and potential mechanism of action of the Astragalus–Scorpion (A–S) drug pair in PCa, in order to provide new insights into the treatment of PCa.
Methods:
Network pharmacology was used to analyze the A–S drug pair and PCa targets. Bioinformatics analysis was used to analyze the LncRNAs with significant differences in PCa. The expression of LC3 protein was detected by immunofluorescence. CCK8 was used to detect cell proliferation. The expressions of GDPD4-2, AC144450.1, LINC01513, AC004009.2, AL096869.1, AP005210.1, and BX119924.1 were detected by RT-qPCR. The expression of the PI3K/AKT/mTOR pathway and autophagy-related proteins were detected by western blot. LC-MS/MS was used to identify the active components of Astragalus and Scorpion.
Results:
A–S drug pair and PCa have a total of 163 targets, which were mainly related to the prostate cancer and PI3K/AKT pathways. A–S drug pair inhibited the formation of PCa, promoted the expression of LC3Ⅱ and Beclin1 proteins, and inhibited the expression of P62 and PI3K–AKT pathway proteins in PCa mice. Astragaloside IV and polypeptide extract from scorpion venom (PESV) were identified as the main active components of the A–S drug pair. GDPD4-2 was involved in the treatment of PCa by Astragaloside IV-PESV. Silencing GDPD4-2 reversed the therapeutic effects of Astragaloside IV-PESV by regulating the PI3K/AKT/mTOR pathway.
Conclusion:
Astragaloside IV-PESV is the main active components of A–S drug pair treated PCa by regulating the GDPD4-2/PI3K–AKT/mTOR pathway and autophagy.
Drug resistance is the major cause of increasing mortality in prostate cancer (PCa). Therefore, it an urgent to develop more effective therapeutic agents for PCa treatment. Xihuang pills (XHP) have ...been recorded as the efficient anti-tumor formula in ancient Chinese medical literature, which has been utilized in several types of cancers nowadays. However, the effect protective role of XHP on the PCa and its underlying mechanisms are still unclear.
The active ingredients of XHP were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and BATMAN-TCM. The potential targets of PCa were acquired from the Gene Cards and OMIM databases. R language and Perl language program were utilized to clarify the interaction between the PCa-related targets and the potential targets of XHP. The potential targets of XHP for prostate cancer were gathered from the Gene ontology and KEGG pathway. Furthermore, cell proliferation assays were verified by PC3 and LNCaP cells. The efficacy and potential mechanism tests were confirmed by the PCa PC3 cells and mice subcutaneous transplantation. The effects of PI3K/Akt/mTOR-related proteins on proliferation, apoptosis, and cell cycle of PCa cells were measured by the Cell Counting Kit-8(CCK8), TUNEL assay, real-time quantitative reverse transcription PCR (QRT-PCR), and Western Blotting, respectively.
The active components of four traditional Chinese medicines in XHP were searched on the TCMSP and Batman TCM database. The biological active components of XHP were obtained as OB ≥30% and DL ≥0.18. The analysis of gene ontology and KEGG pathway identified the PI3K/Akt/mTOR signaling pathway as the XHP-associated pathway. Collectively, the results of
and
experiments showed that XHP had the effect of inhibiting on the proliferation of PC3 and LNCaP cells. XHP promoted the apoptosis and restrained the cell cycle and invasion of the PC3 cells and subcutaneous transplantation. Meanwhile, the suppression of XHP on the level of expression of PI3K, Akt, and mTOR-pathway-related pathway proteins has been identified in a dose-dependent manner.
PI3K/Akt/mTOR pathway-related pathway proteins were confirmed as the potential XHP-associated targets for PCa. XHP can suppress the proliferation of prostate cancer via inhibitions of the PI3K/Akt/mTOR pathway.
Background:
Knee osteoarthritis (KOA), a chronic degenerative disease, is mainly characterized by destruction of articular cartilage and inflammatory reactions. At present, there is a lack of ...economical and effective clinical treatment. Zhuifeng Tougu (ZFTG) capsules have been clinically approved for treatment of OA as they relieve joint pain and inflammatory manifestations. However, the mechanism of ZFTG in KOA remains unknown.
Purpose:
This study aimed to investigate the effect of ZFTG on the TLR4/MyD88/NF-κB signaling pathway and its therapeutic effect on rabbits with KOA.
Study design:
In vivo
, we established a rabbit KOA model using the modified Videman method.
In vitro
, we treated chondrocytes with IL-1β to induce a pro-inflammatory phenotype and then intervened with different concentrations of ZFTG. Levels of IL-1β, IL-6, TNF-α, and IFN-γ were assessed with histological observations and ELISA data. The effect of ZFTG on the viability of chondrocytes was detected using a Cell Counting Kit-8 and flow cytometry. The protein and mRNA expressions of TLR2, TLR4, MyD88, and NF-κB were detected using Western blot and RT-qPCR and immunofluorescence observation of NF-κB p65 protein expression, respectively, to investigate the mechanism of ZFTG in inhibiting inflammatory injury of rabbit articular chondrocytes and alleviating cartilage degeneration.
Results:
The TLR4/MyD88/NF-κB signaling pathway in rabbits with KOA was inhibited, and the levels of IL-1β, IL-6, TNF-α, and IFN-γ in blood and cell were significantly downregulated, consistent with histological results. Both the protein and mRNA expressions of TLR2, TLR4, MyD88, NF-κB, and NF-κB p65 proteins in that nucleus decreased in the ZFTG groups. Moreover, ZFTG promotes the survival of chondrocytes and inhibits the apoptosis of inflammatory chondrocytes.
Conclusion:
ZFTG alleviates the degeneration of rabbit knee joint cartilage, inhibits the apoptosis of inflammatory chondrocytes, and promotes the survival of chondrocytes. The underlying mechanism may be inhibition of the TLR4/MyD88/NF-kB signaling pathway and secretion of inflammatory factors.
Prostate cancer, marked by a high incidence and mortality rate, presents a significant challenge, especially in the context of castration-resistant prostate cancer (CRPC) with limited treatment ...options due to drug resistance. This study aims to explore the anti-tumor effects of Xihuang Pills (XHP) on CRPC, focusing on metabolic reprogramming and the Wnt/β-catenin pathway.
In vitro and in vivo biofunctional assays were employed to assess the efficacy and mechanisms of XHP. Subcutaneous xenografts of PC3 in mice served as an in vivo model to evaluate XHP's anti-tumor activity. Tumor volume, weight, proliferation, and apoptosis were monitored. Various assays, including CCK8, TUNEL assay, QRT-PCR, and Western Blotting, were conducted to measure metabolic reprogramming, proliferation, apoptosis, and cell cycle in prostate cancer cells. RNA-seq analysis predicted XHP's impact on prostate cancer, validating the expression of Wnt/β-catenin-related proteins and mRNA. Additionally, 58 compounds in XHP were identified via LC-MS/MS, and molecular docking analysis connected these compounds to key genes.
In vitro and in vivo experiments demonstrated that XHP significantly inhibited CRPC cell viability, induced apoptosis, and suppressed invasion and migration. mRNA sequencing revealed differentially expressed genes, with functional enrichment analysis indicating modulation of key biological processes. XHP treatment downregulated Wnt signaling pathway-related genes, including CCND2, PRKCG, and CCN4. Moreover, XHP effectively inhibited glucose uptake and lactate production, leading to reduced HIF-1α and glycolytic enzymes (GLUT1, HK2, PKM2), suggesting its potential in attenuating the Warburg effect. Molecular docking analysis suggested a plausible interaction between XHP's active compounds and Wnt1 protein, indicating a mechanism through which XHP modulates the Wnt/β-catenin pathway.
XHP demonstrated remarkable efficacy in suppressing the growth, proliferation, apoptosis, migration, and invasiveness of prostate tumors. The interaction between XHP's active constituents and Wnt1 was evident, leading to the inhibition of Wnt1 and downstream anti-carcinogenic factors, thereby influencing the β-catenin/HIF-1α-mediated glycolysis.
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