Single-cell multi-omics in the study of digestive system cancers.

Digestive system cancers are prevalent diseases with a high mortality rate, posing a significant threat to public health and economic burden. The diagnosis and treatment of digestive system cancer confront conventional cancer problems, such as tumor heterogeneity and drug resistance. Single-cell sequencing (SCS) emerged at times required and has developed from single-cell RNA-seq (scRNA-seq) to the single-cell multi-omics era represented by single-cell spatial transcriptomics (ST). This article comprehensively reviews the advances of single-cell omics technology in the study of digestive system tumors. While analyzing and summarizing the research cases, vital details on the sequencing platform, sample information, sampling method, and key findings are provided. Meanwhile, we summarize the commonly used SCS platforms and their features, as well as the advantages of multi-omics technologies in combination. Finally, the development trends and prospects of the application of single-cell multi-omics technology in digestive system cancer research are prospected.

Au nanorod assembly for sensitive SERS detection of airway inflammatory factors in sputum.

In this paper, we demonstrate a surface-enhanced Raman spectroscopy (SERS) biosensor based on the self-assembly of gold nanorods (AuNRs) for the specific detection of airway inflammatory factors in diluted sputum. The AuNR surface was modified with an antibody that was able to specifically recognize an airway inflammatory factor, interleukin-5 (IL-5), so that a end-to-end self-assembly system could be obtained, resulting in an order of magnitude amplification of the Raman signal and greatly improved sensitivity. Meanwhile, the outer layer of the biosensor was coated with silicon dioxide, which improved the stability of the system and facilitated its future applications. When the detected concentration was in the range of 0.1-50 pg/mL, the SERS signal generated by the sensor showed a good linear relationship with the IL-5 concentration. Moreover, it had satisfactory performance in diluted sputum and clinical subjects with asthma, which could achieve sensitive detection of the airway inflammatory factor IL-5. Overall, the developed biosensor based on the SERS effect exhibited the advantages of rapid and sensitive detecting performance, which is suitable for monitoring airway inflammatory factors in sputum.

Application effect of head-mounted mixed reality device combined with 3D printing model in neurosurgery ventricular and hematoma puncture training.

BACKGROUND: The purpose of this study was to explore the applicability of application effect of head-mounted mixed reality (MR) equipment combined with a three-dimensional (3D) printed model in neurosurgical ventricular and haematoma puncture training. METHODS: Digital Imaging and Communications in Medicine (DICOM) format image data of two patients with common neurosurgical diseases (hydrocephalus and basal ganglia haemorrhage) were imported into 3D Slicer software for 3D reconstruction, saved, and printed using 3D printing to produce a 1:1-sized head model with real person characteristics. The required model (brain ventricle, haematoma, puncture path, etc.) was constructed and imported into the head-mounted MR device, HoloLens, and a risk-free, visual, and repeatable system was designed for the training of junior physicians. A total of 16 junior physicians who studied under this specialty from September 2020 to March 2022 were selected as the research participants, and the applicability of the equipment and model during training was evaluated with assessment score sheets and questionnaires after training. RESULTS: According to results of the assessment and questionnaire, the doctors trained by this system are more familiar with the localization of the lateral anterior ventricle horn puncture and the common endoscopic surgery for basal ganglia haemorrhage, as well as more confident in the mastery of these two operations than the traditional training methods. CONCLUSIONS: The use of head-mounted MR equipment combined with 3D printing models can provide an ideal platform for the operation training of young doctors. Through holographic images created from the combination of virtual and real images, operators can be better immersed in the operation process and deepen their understanding of the operation and related anatomical structures. The 3D printed model can be repeatedly reproduced so that doctors can master the technology, learn from mistakes, better achieve the purpose of teaching and training, and improve the effect of training.

The effect of background elements of pictures on the visual attention among ASD children with intellectual disabilities, children with intellectual disabilities and typical development: Evidence from eye-tracking and fMRI.

Traditional picture books for children come with colourful images and a multitude of elements to attract attention and increase the reading interest of typical-developing (TD) children. However, children with Autism Spectrum Disorder (ASD) are less capable of filtering out unimportant elements in pictures and focusing on social items (e.g., human faces). This study proposed that the removal of background and less important elements in the pictures of children's storybooks could facilitate better attention and enhance children with ASD's focus on the main object and thus the intended meaning of the storybook. We adopted pictures from a well-known children's book and modified them by removing the inessential background elements. Then, ASD children with intellectual disabilities (ASD+ID) (n = 40), children with ID (n = 38) and TD (n = 40) were asked to view the original and modified pictures in an eye-tracking experiment, respectively. Additionally, brain activation of ASD+ID participants (n = 10) was recorded as they were viewing those pictures in an fMRI scan. Eye-tracking found that ASD+ID children viewed the modified pictures with significantly longer average fixations, fewer fixations, fewer saccades, and higher fixation/saccade duration ratio. Contrary to the original pictures, no significant differences were found among ASD+ID, ID only and TD. Especially, ASD+ID group showed highly similar visual patterns to the TD participants when viewing the modified pictures and particularly focusing on the main character in the pictures. Additional fMRI evidence on ASD+ID group also revealed that modified pictures were associated with enhanced activation in bilateral fusiform gyri as compared to those from original pictures, which might suggest increased visual attention. Theoretical and practical implications were discussed in light of our findings.

Brain structural correlates of postoperative axial pain in degenerative cervical myelopathy patients following posterior cervical decompression surgery: a voxel-based morphometry study.

OBJECTIVE: To investigate the brain structural correlates of postoperative axial pain (PAP) in degenerative cervical myelopathy (DCM) following posterior cervical decompression surgery. METHODS: Structural images with high-resolution T1 weighting were collected from 62 patients with DCM and analyzed, in addition to 42 age/gender matched subjects who were healthy. Voxel-based morphometry (VBM) was analyzed, grey matter volume (GMV) was computed. One-way ANOVA was performed to reveal the GMV differences among DCM patients with PAP, patients without PAP and healthy controls (HC). Post-hoc analyses were conducted to identify the pair-wise GMV differences among these three groups. Analyses of correlations were conducted to uncover the link between clinical measurements and GMV variations. Last, support vector machine (SVM) was conducted to test the utility of GMV for classifying PAP and nPAP DCM patients. RESULTS: Three main findings were observed: [1] Compared to healthy controls, DCM patients showed a significantly lower GMV in the precuneus preoperatively. DCM patients with PAP also exhibited a lower GMV within precuneus than those without; [2] In DCM patients with PAP, the precuneus GMV was inversely related to the postoperative pain intensity; [3] Moreover, successful classification between PAP and nPAP were observed via SVM based on precuneus GMV as features. CONCLUSION: In summary, our results indicate that precuneus GMV may be linked to PAP in DCM, and could be employed to forecast the emergence of PAP in DCM patients.

Mettl3 Mediated m6A Methylation Involved in Epithelial-Mesenchymal Transition by Targeting SOCS3/STAT3/SNAI1 in Cigarette Smoking-Induced COPD.

Purpose: Persistent inflammation and epithelial-mesenchymal transition are essential pathophysiological processes in chronic obstructive pulmonary disease (COPD) and involve airway remodeling. m6A methylation modification was discovered to play an important role in various diseases. Nevertheless, the regulatory role of m6A methylation has not yet been investigated in cigarette smoking-induced COPD. The study aims to explore the regulatory role of m6A methylation in cigarette smoking-induced COPD. Patients and Methods: In this study, two Gene Expression Omnibus (GEO) datasets were first utilized to analyze the expression profiles of m6A RNA methylation regulators in COPD. We then established a cell model of COPD by exposing human bronchial epithelial cells (HBECs) to cigarette smoke extract (CSE) in vitro and detected the expression of m6A writer Mettl3 and EMT phenotype markers. RNA interference, cycloleucine, RT-qPCR, western blot, MeRIP-sequencing, and cell migration assay were performed to investigate the potential effect of Mettl3 on the EMT process in CSE-induced HBECs. Results: Our results showed that Mettl3 expression was significantly elevated in cigarette smoking-induced COPD patients and in a cellular model of COPD. Furthermore, Mettl3 silence and cycloleucine treatment inhibited the EMT process of HBECs caused by CSE. Mechanically, Mettl3 silence weakens the m6A methylation of SOCS3 mRNA to enhance the protein expression of SOCS3, inhibiting CSE-induced SOCS3/STAT3/SNAI1 signaling and EMT processes in HBECs. Conclusion: Our study inferred that Mettl3-mediated m6A RNA methylation modification modulates CSE-induced EMT by targeting SOCS3 mRNA and ultimately serves as a crucial regulator in the emergence of COPD. This conclusion reinforces the regulatory role of m6A methylation in COPD.

Profiling of metabolites, proteins, and protein phosphorylation in silica-exposed BEAS-2B epithelial cells.

Silicosis is an uncurable occupational disease induced by crystalline silica. Increased prevalence of silicosis has resulted in the increased need for development of treatment options. Although macrophages respond first to silica, epithelial cells are also involved in silicosis. However, changes in protein and metabolite levels have not been reported simultaneously. We used mass spectrometry to profile changes in metabolites, proteins, and phosphorylation in silica-exposed BEAS-2B epithelial cells. Silica exposure increased TCA cycle, alanine, aspartate and glutamate metabolism, and aerobic glycolysis activity. In addition, protein levels in the endoplasmic reticulum were significantly altered, and phosphorylation of MAPK signaling proteins was increased. The results of this study increased understanding the role of epithelial cells in silicosis.

Age-to-Glasgow Coma Scale score ratio predicts gastrointestinal bleeding in patients with primary intracerebral hemorrhage.

Objective: Recent clinical studies have demonstrated that advanced age and low initial Glasgow Coma Scale (GCS) score were independent predictors of gastrointestinal bleeding (GIB) in patients with primary intracerebral hemorrhage (ICH). However, used singly, age and GCS score have their respective shortcomings in predicting the occurrence of GIB. This study aimed to investigate the association between the age-to-initial GCS score ratio (AGR) and the risk of GIB following ICH. Methods: We conducted a single-center, retrospective observational study of consecutive patients presenting with spontaneous primary ICH at our hospital from January 2017 through January 2021. Patients who fulfilled the inclusion and exclusion criteria were categorized into GIB and non-GIB groups. Univariate and multivariate logistic regression analyses were implemented to identify the independent risk factors for the occurrence of GIB, and a multicollinearity test was performed. Furthermore, one-to-one matching was conducted to balance important patient characteristics by the groups' propensity score matching (PSM) analysis. Results: A total of 786 consecutive patients fulfilled the inclusion/exclusion criteria for the study, and 64 (8.14%) patients experienced GIB after primary ICH. Univariate analysis revealed that patients with GIB were significantly older [64.0 (55.0-71.75) years vs. 57.0 (51.0-66.0) years, p = 0.001] and had a higher AGR [7.32 (5.24-8.96) vs. 5.40 (4.31-7.11), p < 0.001] and a lower initial GCS score [9.0 (7.0-11.0) vs. 11.0 (8.0-13.0), p < 0.001]. The multicollinearity test revealed that no multicollinearity was observed in the multivariable models. Multivariate analysis showed that the AGR was a significant independent predictor of GIB [odds ratio (OR) 1.155, 95% confidence interval (CI) 1.041-1.281, p = 0.007], as well as prior anticoagulation or antiplatelet therapy (OR 0.388, 95% CI 0.160-0.940, p = 0.036) and MV used >24 h (OR 0.462, 95% CI 0.252-0.848, p = 0.013). Receiver operating curve (ROC) analysis illustrated that the optimal cutoff value for the AGR as a predictor for GIB in patients with primary ICH was 6.759 [the area under the curve (AUC) was 0.713 with a corresponding sensitivity of 60.94% and specificity of 70.5%, 95% CI 0.680-0.745, p < 0.001]. After 1:1 PSM, the matched GIB group had significantly higher AGR levels compared with the matched non-GIB group [7.47(5.38-9.32) vs. 5.24(4.24-6.40), p <0.001]. The ROC analysis indicated an AUC of 0.747 (the sensitivity was 65.62%, and the specificity was 75.0%, 95% CI 0.662-0.819, p < 0.001) for AGR levels as an independent predictor of GIB in patients with ICH. In addition, AGR levels were statistically correlated with unfunctional 90-day outcomes. Conclusion: A higher AGR was associated with an increased risk of GIB and unfunctional 90-day outcomes in patients with primary ICH.

Bibliometric and visualization analysis of radiation brain injury from 2003 to 2023.

Background: Over the past two decades, the field of radiation brain injury has attracted the attention of an increasing number of brain scientists, particularly in the areas of molecular pathology and therapeutic approaches. Characterizing global collaboration networks and mapping development trends over the past 20 years is essential. Objective: The aim of this paper is to examine significant issues and future directions while shedding light on collaboration and research status in the field of radiation brain injury. Methods: Bibliometric studies were performed using CiteSpaceR-bibliometrix and VOSviewer software on papers regarding radiation brain injury that were published before November 2023 in the Web of Science Core Collection. Results: In the final analysis, we found 4,913 records written in 1,219 publications by 21,529 authors from 5,007 institutions in 75 countries. There was a noticeable increase in publications in 2014 and 2021. The majority of records listed were produced by China, the United States, and other high-income countries. The largest nodes in each cluster of the collaboration network were Sun Yat-sen University, University of California-San Francisco, and the University of Toronto. Galldiks N, Barnett GH, Langen KJ and Kim JH are known to be core authors in the field. The top 3 keywords in that time frame are radiation, radiation necrosis, and radiation-therapy. Conclusions: The objective and thorough bibliometric analysis also identifies current research hotspots and potential future paths, providing a retrospective perspective on RBI and offering useful advice to researchers choosing research topics. Future development directions include the integration of multi-omics methodologies and novel imaging techniques to improve RBI's diagnostic effectiveness and the search for new therapeutic targets.

A newly identified interaction between nucleolar NPM1/B23 and the HTLV-I basic leucine zipper factor in HTLV-1 infected cells.

Human T-cell leukemia virus type 1 is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia-lymphoma (ATL). The HTLV-1 basic leucine zipper factor (HBZ) has been associated to the cancer-inducing properties of this virus, although the exact mechanism is unknown. In this study, we identified nucleophosmin (NPM1/B23) as a new interaction partner of HBZ. We show that sHBZ and the less abundant uHBZ isoform interact with nucleolar NPM1/B23 in infected cells and HTLV-1 positive patient cells, unlike equivalent antisense proteins of related non-leukemogenic HTLV-2, -3 and-4 viruses. We further demonstrate that sHBZ association to NPM1/B23 is sensitive to RNase. Interestingly, sHBZ was shown to interact with its own RNA. Through siRNA and overexpression experiments, we further provide evidence that NPM1/B23 acts negatively on viral gene expression with potential impact on cell transformation. Our results hence provide a new insight over HBZ-binding partners in relation to cellular localization and potential function on cell proliferation and should lead to a better understanding of the link between HBZ and ATL development.

Landscape of B Cell Receptor Repertoires in COVID-19 Patients Revealed Through CDR3 Sequencing of Immunoglobulin Heavy and Light Chains.

The outbreak and persistence of coronavirus disease 2019 (COVID-19) threaten human health. B cells play a vital role in fighting the infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite many studies on the immune responses in COVID-19 patients, it is still unclear how B cell receptor (BCR) constituents, including immunoglobulin heavy (IGHs) and light chains (IGLs), respond to SARS-CoV-2 in patients with varying symptoms. In this study, we conducted complementarity-determining region 3 (CDR3) sequencing of BCR IGHs and IGLs from the peripheral blood of COVID-19 patients and healthy donors. The results showed significantly reduced clonal diversity, more expanded clones, and longer CDR3 lengths of IGH and IGL in COVID-19 patients than those in healthy individuals. The IGLs had a much higher percentage of VJ skew usage (47.83% IGLV and 42.86% IGLJ were significantly regulated) than the IGHs (12.09% IGHV and 0% IGHJ) between the healthy individuals and patients, which indicated the importance of BCR light chains. Furthermore, we found a largely expanded IGLV3-25 gene cluster mostly pairing with IGLJ1 and ILGJ2 in COVID-19 patients and a newly identified upregulated IGLJ1 gene and IGLJ2+IGLV13-21 recombination, both of which are potential sources of SARS-CoV-2-targeting antibodies. Our findings on specific immune B-cell signatures associated with COVID-19 have clinical implications for vaccine and biomarker development for disease diagnosis.

A novel signal enhancement strategy for the detection of DNA oxidative damage biomarker 8-OHdG based on the synergy between ß-CD-CuNCs and multi-walled carbon nanotubes.

OBJECTIVE: To propose a novel signal enhancement strategy based on the synergy between ß-CD-CuNCs and multi-walled carbon nanotubes (MWCNTs) for the detection of DNA oxidative damage biomarker 8-Hydroxy-2'-deoxyguanosine (8-OHdG). METHODS: The sensor was constructed with the ß-CD-CuNCs-MWCNTs-nafion film and successfully used for the quantitative detection of 8-OhdG in the presence of biomolecules such as ascorbic acid (AA) and uric acid (UA). To investigate the surface morphology of the modified electrode, Transmission Electron Microscopy (TEM), Cyclic Voltammetry (CV) and Electrochemical Impedance Spectroscopy (EIS) were performed on bare and modified electrodes. RESULTS: According to Differential Pulse Voltammetry (DPV) results, there was a linear relationship between peak current and concentration of 8-OhdG, ranging from 1.0×10-7 to 1.0×10-6 mol/L (R2=0.9926) and 1.0×10-6 to 2.0×10-5 mol/L (R2=0.9933). The detection limit (S/N=3) was 33 nmol/L. CONCLUSIONS: The proposed sensor had been successfully applied to the determination of 8-OHdG in human urine samples with high recovery rates.

Luteolin Prevents Cardiac Dysfunction and Improves the Chemotherapeutic Efficacy of Doxorubicin in Breast Cancer.

Background: Doxorubicin (Dox) is one of the most effective chemotherapy agents used in the treatment of solid tumors and hematological malignancies. However, it causes dose-related cardiotoxicity that may lead to heart failure in patients. Luteolin (Lut) is a common flavonoid that exists in many types of plants. It has been studied for treating various diseases such as hypertension, inflammatory disorders, and cancer. In this study, we evaluated the cardioprotective and anticancer effects of Lut on Dox-induced cardiomyopathy in vitro and in vivo to explore related mechanisms in alleviating dynamin-related protein (Drp1)-mediated mitochondrial apoptosis. Methods: MTT and LDH assay were used to determine the viability and toxicity of cardiomyocytes treated with Dox and Lut. Flow cytometry was used to examine ROS levels, and electron and confocal microscopy was employed to assess the mitochondrial morphology. The level of apoptosis was examined by Hoechst 33258 staining. The protein levels of myocardial fission protein and apoptosis-related protein were examined using Western blot. Transcriptome analysis of the protective effect of Lut against Dox-induced cardiac toxicity in myocardial cells was performed using RNA sequencing technology. The protective effects of Lut against cardiotoxicity mediated by Dox in zebrafish were quantified. The effect of Lut increase the antitumor activity of Dox in breast cancer both in vitro and in vivo were further employed. Results: Lut ameliorated Dox-induced toxicity in H9c2 and AC16 cells. The level of oxidative stress was downregulated by Lut after Dox treatment of myocardial cells. Lut effectively reduced the increased mitochondrial fission post Dox stimulation in cardiomyocytes. Apoptosis, fission protein Drp1, and Ser616 phosphorylation were also increased post Dox and reduced by Lut. In the zebrafish model, Lut significantly preserved the ventricular function of zebrafish after Dox treatment. Moreover, in the mouse model, Lut prevented Dox-induced cardiotoxicity and enhanced the cytotoxicity in triple-negative breast cancer by inhibiting proliferation and metastasis and inducing apoptosis.

Recent advances in the treatment of traumatic brain injury with autologous and non-autologous multipotent stem and progenitor cells: preclinical models and clinical trials.

Traumatic brain injury (TBI) is a global health issue which causes millions of deaths and disabilities every year. The survivors of TBI may suffer from sensorimotor dysfunction, memory and cognitive disturbances, hearing and vision deficits, and various psychological problems. The primary insult may damage neurons, cerebral vessels and the blood-brain barrier, causing reactive astrogliosis and immune response with further damaging consequences. TBI lacks effective therapy. The currently available clinical treatment options include hyperbaric oxygenation, brain stimulation and rehabilitation. In recent years, the research on stem cell treatment of TBI has received extensive attention. Various types of stem cells, such as four types of mesenchymal stem cells, neural stem cells and olfactory ensheathing cells have been tried to treat TBI in clinical trials and preclinical models. This article reviews the research of autologous and non-autologous multipotent stem and progenitor cells for the treatment of TBI in both clinical and preclinical settings.

Mast cells-derived exosomes worsen the development of experimental cerebral malaria.

Cerebral malaria (CM) is the most severe neurological complication caused by Plasmodium falciparum infection. The accumulating evidence demonstrated that mast cells (MCs) and its mediators played a critical role in mediating malaria severity. Earlier studies identified that exosomes were emerging as key mediators of intercellular communication and can be released from several kinds of MCs. However, the potential functions and pathological mechanisms of MCs-derived exosomes (MCs-Exo) impacting on CM pathogenesis remain largely unknown. Herein, we utilized an experimental CM (ECM) model (C57BL/6 mice infected with P. berghei ANKA strain), and then intravenously (i.v.) injected MCs-Exo into P. berghei ANKA-infected mice to unfold this mechanism and investigate the effect of MCs-Exo on ECM pathogenies. We also used an in vitro model by investigating the pathogenesis development of brain microvascular endothelial cells line (bEnd.3 cells) co-cultured with P. berghei ANKA blood-stage soluble antigen (PbAg) after MCs-Exo treatment. The higher numbers of MCs and levels of MCs degranulation were observed in skin, cervical lymph node, and brain of ECM mice than those of the uninfected mice. Exosomes were successfully isolated from culture supernatants of mouse MCs line (P815 cells) and characterized by spherical vesicles with the diameter of 30-150 nm, and expression of typical exosomal markers (e.g., CD9, CD63, and CD81). The i.v. injection of MCs-Exo dramatically elevated incidence of ECM in the P. berghei ANKA-infected mice, exacerbated liver and brain histopathological damage, promoted Th1 cytokine response, aggravated brain vascular endothelial activation and blood brain barrier breakdown in ECM mice. In addition, the treatment of MCs-Exo led to the decrease of cells viability and mRNA levels of Ang-1, ZO-1, and Claudin-5, but increase of mRNA levels of Ang-2, CCL2, CXCL1, and CXCL9 in bEnd.3 cells co-cultured with PbAg in vitro. Taken together, our data indicated that MCs-Exo could worsen pathogenesis of ECM in mice.

The qualitative accuracy of clinical dermatophytes via matrix-assisted laser desorption ionization-time of flight mass spectrometry: A meta-analysis.

Dermatophytes are an important part of superficial fungal infections, and accurate diagnosis is paramount for successful treatment. Recently, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has emerged as a powerful tool to identify clinical pathogens; its advantages are cost-effectiveness, rapid detection, and high accuracy. However, as the accurate identification of clinical dermatophytes via MALDI-TOF MS has still not been fully evaluated, we performed a meta-analysis for its systematic evaluation. Fifteen eligible studies were involved and showed high accuracy with an identification ratio of 0.96 (95% CI = 0.92─1.01) and 0.91 (95% CI = 0.86─0.96) at the genus and species levels, respectively. The results showed higher accuracy ratio of Vitek MS (91%) than MALDI Biotyper (85%). Dermatophytes such as Trichophyton interdigitale (0.99, 95% CI = 0.97─1.02), T. mentagrophytes var interdigitale (1.00, 95% CI = 0.98─1.02), and Microsporum canis (0.97, 95% CI = 0.89─1.04) showed high accuracy in detected clinical dermatophytes. Moreover, a library with self-built database set up by laboratories showed higher accuracy than commercial database, and 15-day cultivation for dermatophytes showed highest accuracy considering culture time. High heterogeneity was observed and decreased only with the subgroup analysis of species. The subgroup analysis of mass spectrometry, library database, and culture time also exhibited high heterogeneity. In summary, our results showed that MALDI-TOF MS could be used for highly accurate detection of clinically pathogenic dermatophytes, which could be an alternative diagnostic method in addition to morphological and molecular methods.

This meta-analysis comprehensively investigated the qualitative accuracy of clinical dermatophytes through MALDI-TOF MS. Owing to the high accuracy observed at both genus and species levels, this approach could be an alternative diagnostic method in addition to morphological and molecular methods.

Safety, tolerability, and pharmacokinetics of oral baicalein tablets in healthy Chinese subjects: A single-center, randomized, double-blind, placebo-controlled multiple-ascending-dose study.

Baicalein is a biologically important flavonoid in extracted from the Scutellaria baicalensis Georgi, which can effectively inhibit the influenza virus. This study aimed to analyze the safety and pharmacokinetic (PK) characteristics of baicalein tablets in healthy Chinese subjects and provide more information for phase II clinical trials. In this multiple-ascending-dose placebo-controlled trial, 36 healthy subjects were randomized to receive 200, 400, and 600 mg of baicalein tablet or placebo once daily on day 1 and day 10, 3 times daily on days 4-9. All groups were intended to produce safety and tolerability outcomes (lowest dose first). Blood and urine samples were collected from subjects in the 600 mg group for baicalein PK analysis. Our study had shown that Baicalein tablet was generally safe and well-tolerated. All adverse events were mild and resolved without any intervention except one case of fever reported in the 600 mg group, which was considered as moderate but not related with baicalein as judged by the investigator. Oral baicalein tablets were rapidly absorbed with peak plasma levels being reached within 2 h after multiple administration. The highest urinary excretion of baicalein and its metabolites peaked in 2 h, followed by 12 h, with a double peak trend.

Traditional Chinese Medicine as an adjunct therapy in the treatment of idiopathic membranous nephropathy: A systematic review and meta-analysis.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome in adults involving multiple targets and factors. The effect of conservative nonimmunosuppressive or immunosuppressive therapies is unsatisfactory and with many side effects. Traditional Chinese medicine (TCM) can regulate immune function and improve kidney function. PURPOSE: To evaluate the total effective rate, curative rate, recurrence rate and adverse events of TCM alone or TCM as an adjunctive therapy for IMN. METHODS: Randomized controlled trials (RCT) comparing either TCM alone or the combination of TCM to western medicine (WM) therapies for patients with IMN were retrieved by searching English and Chinese database. Risk of bias summary was used to assess the methodological quality of eligible studies. Dichotomous data were presented using odds ratios (OR). The primary outcome measure was the total effective rate. Secondary outcomes included curative rate, recurrence rate and adverse events. RESULTS: 29 RCTs involving 1883 participants met the inclusion criteria. There was no statistically significant difference between the therapy of TCM alone and WM on the total effective rates (OR: 2.00; 95% CI: 0.80-4.98; P = 0.14) and curative rate (OR: 1.66; 95%CI: 0.66-4.22; p = 0.28). However, compared to basic treatment or immunosuppressive therapies alone, results showed that TCM as an adjunctive therapy had beneficial effects on the total effective rate (OR: 2.59; 95% CI: 1.38-4.86; P = 0.003 and OR: 3.01; 95% CI: 2.25-4.04; P < 0.00001) and curative rate (OR: 3.01; 95%CI: 1.24-7.28; p = 0.01 and OR: 1.73; 95%CI: 1.10-2.71; p = 0.02). In addition, the combination of TCM treatment could reduce the recurrence rate (OR: 0.28; 95% CI: 0.12-0.68; P = 0.004) and adverse reactions (OR: 0.38; 95% CI: 0.27-0.54; p < 0.00001). CONCLUSION: The results indicate that TCM is well-tolerated for the treatment of IMN. However, there remains a need for large-scale and high-quality trials.

Safety, tolerability, pharmacokinetics, and food effect of baicalein tablets in healthy Chinese subjects: A single-center, randomized, double-blind, placebo-controlled, single-dose phase I study.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis (Huang-Qin in Chinese) is a dry root of the perennial herb Scutellaria baicalensis Georgi, which has been used extensively in current prescriptions. Scutellaria baicalensis is an herb high in flavonoids, and baicalein is the one flavonoid found in the highest amount in Scutellaria baicalensis. AIM OF THE STUDY: Influenza virus could cause mild respiratory tract illness to severe pneumonia and even death. Baicalein has been proved to be one of the effective components against the influenza virus. However, there have been few reports on human trials of baicalein. The purpose of this study was to evaluate the safety of baicalein in vivo and analyze its pharmacokinetic characteristics. MATERIALS AND METHODS: Three randomized studies were conducted to evaluate the pharmacokinetics (PK), safety, tolerability, and food effects of baicalein tablets. In the 7-month single-dose safety study, 60 subjects were enrolled and randomized to receive 100-800 mg baicalein tablets or placebo. In the single-dose PK study, 40 subjects were enrolled and randomized to receive 200 mg, 400 mg, 600 mg, 800 mg baicalein tablets. In the study of food effect on PK of baicalein, an additional 10 subjects were enrolled in the 400 mg group, this part of the trial lasted for 7 months. Blood and urine samples for PK analysis were collected at a pre-specified time. PK properties in both fasted and fed states were evaluated, as well as safety and tolerability. RESULTS: Among the 80 subjects who were evaluable for the single-dose safety and tolerability, 56 adverse events (AEs) were observed in 32/80 subjects, of which 49 events were from 28/68 subjects in baicalein group and 7 events were from 4/12 subjects in placebo group. All AEs were mild and resolved without any medical intervention. The most common AEs were elevated high-sensitivity C-reactive protein (hs-CRP) level and high triglycerides. After a single administration of baicalein tablets (200 mg, 400 mg, 600 mg, or 800 mg), Cmax were 280.44, 628.80, 845.20, 489.55 ng/mL; AUC0-∞ were 2035.57, 2939.31, 4494.88, and 3754.43 h*ng/mL, respectively. And t1/2z ranged from 7.80 to 14.91 h. The exposure of baicalein and its metabolites increased in a less than dose-proportional manner. CONCLUSION: Baicalein tablets within the studied dose range were safe and well-tolerated in healthy Chinese subjects with no serious or severe adverse effects. Further investigation will be needed to assess the safety and efficacy in the target patients.

Repair abilities of mouse autologous adipose-derived stem cells and ShakeGel™3D complex local injection with intrauterine adhesion by BMP7-Smad5 signaling pathway activation.

BACKGROUND: The objective was to explore the therapeutic effect of autologous adipose-derived stem cells (ADSCs) combined with ShakeGel™3D transplantation to activate the BMP7-Smad5 signaling pathway to treat intrauterine adhesions (IUA). METHODS: Autologous ADSCs were isolated and then merged with ShakeGel™3D. The IUA model was established by mechanical injury. The third generation of autologous ADSCs was injected directly into the uterus in combination with ShakeGel™3D. After 7 days of treatment, endometrial morphology, number of endometrial glands, endometrial fibrosis area, and fibrosis biomarker analysis by RT-PCR and IHC were examined. BMP7 and phosphorylation of Smad5 were also detected, and the recovery of infertility function in treated mice was evaluated. RESULTS: Fluorescence-activated cell sorting (FACS) showed that autologous ADSCs expressed CD105 (99.1%), CD29 (99.6%), and CD73 (98.9%). Autologous ADSCs could still maintain a good growth state in ShakeGel™3D. Histological examination revealed that the number of endometrial glands increased significantly, and the area of fibrosis decreased. At the same time, the expression of BMP7 and Smad5 in the ADSCs + Gel group was significantly upregulated, and the final reproductive function of this group was partly recovered. CONCLUSIONS: Autologous ADSCs can be used in combination with ShakeGel™3D to maintain functionality and create a viable three-dimensional growth environment. The combined transplantation of autologous ADSCs and ShakeGel™3D promotes the recovery of damaged endometrial tissue by increasing BMP7-Smad5 signal transduction, resulting in endometrium thickening, increased number of glands, and decreased fibrosis, leading to restoration of partial fertility.