A new direction in Chinese herbal medicine ameliorates for type 2 diabetes mellitus: Focus on the potential of mitochondrial respiratory chain complexes.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes is a common chronic disease. Chinese herbal medicine (CHM) has a history of several thousand years in the treatment of diabetes, and active components with hypoglycemic effects extracted from various CHM, such as polysaccharides, flavonoids, terpenes, and steroidal saponins, have been widely used in the treatment of diabetes. AIM OF THE STUDY: Research exploring the potential of various CHM compounds to regulate the mitochondrial respiratory chain complex to improve type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: The literature data were primarily obtained from authoritative databases such as PubMed, CNKI, Wanfang, and others within the last decade. The main keywords used include "type 2 diabetes mellitus", "Chinese medicine", "Chinese herbal medicine", "mitochondrial respiratory chain complex", and "mitochondrial dysfunction". RESULTS: Chinese herbal medicine primarily regulates the activity of mitochondrial respiratory chain complexes in various tissues such as liver, adipose tissue, skeletal muscle, pancreatic islets, and small intestine. It improves cellular energy metabolism through hypoglycemic, antioxidant, anti-inflammatory and lipid-modulating effects. Different components of CHM can regulate the same mitochondrial respiratory chain complexes, while the same components of a particular CHM can regulate different complex activities. The active components of CHM target different mitochondrial respiratory chain complexes, regulate their aberrant changes and effectively improve T2DM and its complications. CONCLUSION: Chinese herbal medicine can modulate the function of mitochondrial respiratory chain complexes in various cell types and exert their hypoglycemic effects through various mechanisms. CHM has significant therapeutic potential in regulating mitochondrial respiratory chain complexes to improve T2DM, but further research is needed to explore the underlying mechanisms and conduct clinical trials to assess the safety and efficacy of these medications. This provides new perspectives and opportunities for personalized improvement and innovative developments in diabetes management.

Comparison of ASSR and frequency specificity ABR induced by NB CE-Chirp for prediction of behavioral hearing thresholds in children with conductive hearing loss.

BACKGROUND: Electrophysiological tests are often used to evaluate hearing loss in infants and young children with conductive hearing loss, no matter to quantify or characterize. However, there are advantages and disadvantages associated with the various electrophysiological tests that are currently available. Therefore, there is no gold standard test. This study aimed to compare the value of narrow-band (NB) CE-Chirp-induced auditory steady-state response (ASSR) and auditory brainstem response (ABR) for assessing hearing thresholds in children with conductive hearing loss. We hope to identify an effective electrophysiological testing method to evaluate conductive hearing loss and provide a reference for clinical hearing assessment of infants with conductive hearing loss. SUBJECTS: and Methods: We selected 27 children (41 ears) aged 3-6 years with otitis media with effusion (OME). Within 1 day, they underwent behavioral audiometry and NB CE-Chirp-induced ASSR and ABR tests in sequence. Pearson's correlation analysis was performed to compare behavioral audiometry thresholds and ASSR and ABR response thresholds at 500, 1000, 2000, and 4000 Hz. RESULTS: The behavioral audiometry thresholds of all children were strongly correlated with the response thresholds of the two electrophysiological tests, with correlation coefficients of 0.659, 0.605, 0.723, and 0.857 for ASSR, and 0.587, 0.684, 0.753, and 0.802 for ABR. The proportion of children with a difference of ≤10 dB between ASSR and behavioral audiometry thresholds or between ABR and behavioral audiometry thresholds was not high, especially in the low frequencies. ABR results were superior to ASSR results in terms of predicting actual hearing levels. At 0.5, 1, 2, and 4 kHz, the average differences between the behavioral hearing thresholds and ASSR thresholds in the 41 ears were 5.6, 5.7, 2, and 5.6 dB, respectively. The average differences between behavioral hearing thresholds and ABR thresholds was -5.6, -1.4, -6.8, and 3.2 dB, respectively. The hearing loss configuration of the ASSR exhibited a peaked pattern, similar to behavioral audiometry, whereas the ABR exhibited an ascending pattern. The time to perform the single-ear ASSR test was 5.9 min, whereas the ABR test took 17.0 min. CONCLUSION: ASSR and ABR induced by the NB CE-Chirp correlated well with behavioral audiometry in children with conductive hearing loss. The NB CE-Chirp ASSR has advantages in terms of testing time and hearing configuration evaluation, whereas ABR has better reliability than ASSR. However, the stability of ASSR and ABR induced by the NB CE-Chirp is poor, and the thresholds obtained cannot replace behavioral audiometry in evaluating the true hearing of children with conductive hearing loss. However, ASSR and ABR can be used as auxiliary tests for cross-validation.

Thymoquinone attenuates hepatic lipid accumulation by inducing autophagy via AMPK/mTOR/ULK1-dependent pathway in nonalcoholic fatty liver disease.

Thymoquinone (TQ) has been proved to exert wide-ranging pharmacological activities, with anti-inflammatory, antioxidant, anticonvulsant, antimicrobial, anti-tumor, and antidiabetic properties. In this study, we investigated the beneficial effects of TQ on a high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) in C57BL/6 N mice in vivo and free fatty acid (FFA)-induced human hepatocellular carcinoma HepG2 cells in vitro. Further, the underlying mechanisms of TQ to promote hepatic autophagy were also discovered. Data showed that TQ caused (p < 0.01) body weight reduction, improved glucose homeostasis, alleviated hepatosteatosis, and decreased hepatic lipid accumulation related to the induction of autophagy in HFD-fed mice. In vitro, TQ obviously increased (p < 0.01) autophagic flux in FFA-induced HepG2 cells and consequently reduced the lipid accumulation in combination with activation of AMPK/mTOR/ULK1 signaling pathways. Moreover, pharmacological inhibition of the AMPK pathway by addition with AMPK inhibitor Compound C (CC) or silence of ULK1 by transfection with siRNA(ULK1) into HepG2 cells reversed these beneficial effects of TQ on triggering hepatic autophagy and reducing lipid accumulation (p < 0.01). Taken together, these results suggested that TQ alleviated hepatic lipid accumulation by triggering autophagy through the AMPK/mTOR/ULK1-dependent signaling pathway. Our study supports a potential role for TQ in ameliorating NAFLD.

Isolation, structural characterization and anti-oxidant activity of a novel polysaccharide from garlic bolt.

Allium sativum L. is a widely distributed plant used as a spice, vegetable and medicine. In this study, one novel water-soluble polysaccharide (GBP-1a), with a molecular weight of 15.0 kDa, was isolated from the scape of A. sativum (garlic bolt). GBP-1a consists of galactose, glucose and arabinose at a ratio of 73.29:4.36:1.70. It has a backbone, which is composed of 1,4-linked Galp, with 1,2,6-linked Galp branches and 1-linked Glcp residue. In addition, the anti-oxidant activities of GBP-1a, as well as the two main polysaccharide fractions on ABTS radicals, metal ions and superoxide anion radicals, were evaluated in vitro. This study added new data to the study of polysaccharides from garlic bolt.

Exosomal circRNAs contribute to intestinal development via the VEGF signalling pathway in human term and preterm colostrum.

Human breast milk (HBM) provides essential nutrients for newborn growth and development, and contains a variety of biologically active ingredients that can affect gastrointestinal tract and immune system development in breastfed infants. HBM also contains mRNAs, microRNAs and lncRNAs, most of which are encapsulated in milk-derived exosomes and exhibit various important infant development related biological functions. While previous studies have shown that exosomal circRNAs are involved in the intestinal epithelial cells' proliferation and repair. However, the effect of HBM exosomal circRNAs on intestinal development is not clear. In this study, we identified 6756 circRNAs both in preterm colostrum (PC) and term colostrum (TC), of which 66 were upregulated, and 42 were downregulated (|fold change>2|, p < 0.05) in PC. Pathway analysis showed that the VEGF signalling pathway was involved, and network analysis revealed that the differentially expressed circRNAs bound various miRNAs. Further analyses showed that has_circRNA_405708 and has_circRNA_104707 were involved in the VEGF signalling pathway, and that they all bound various mirRNAs. Exosomes found in preterm colostrum (PC) and term colostrum (TC) promoted VEGF protein expression and induced the proliferation and migration of small intestinal epithelial cells (FHCs). Exosomal circRNAs found in human colostrum (HC) binding to related miRNAs may regulate VEGF signalling, and intestinal development.

Fructo-oligosaccharides lower serum lipid levels and suppress high-fat/high-sugar diet-induced inflammation by elevating serum and gut levels of short-chain fatty acids.

OBJECTIVE: This study aimed to investigate the effects of fructo-oligosaccharides (FOS) on serum lipid levels and to determine the mechanisms underlying these effects and the potential role of inflammation. METHODS: Male C57BL/6 mice received a normal diet, a high-fat/high-sugar (HFS) diet, or an HFS diet supplemented with 10% FOS for 10 weeks. In vivo intestinal and serum short-chain fatty acid (SCFA) levels were measured by gas chromatography. In vivo serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and malonaldehyde (MDA) were also measured. Lipid accumulation was visualized. Reactive oxygen species (ROS) generation was evaluated and apoptosis was quantified. RESULTS: FOS reversed in vivo HFS-induced lipid accumulation in the liver. An HFS diet increased ALT, AST, TC, TG, and LDL serum levels, decreased HDL serum levels, and increased IL-6, TNF-α, 8-OHdG, and MDA levels. These changes were reduced by FOS. FOS also increased intestinal and serum levels of short chain fatty acids (SCFAs). In vitro, SCFAs ameliorated palmitic acid-induced ROS production and apoptosis of HepG2 cells. CONCLUSION: FOS supplementation lowers serum lipid levels and ameliorates HFS-induced inflammation by upregulating SCFAs.

Involvement of the TGFß1- ILK-Akt signaling pathway in the effects of hesperidin in type 2 diabetic nephropathy.

Diabetic nephropathy is one of the manifestations of systemic microangiopathy in diabetes. Hesperetin, a natural flavanone glycoside compound in citrus fruits, has been demonstrated to exert hypoglycemic effects and protect kidney in experimental diabetic animals. The current study was aimed to investigate the mechanisms underlying the hypoglycemic effects of hesperetin in high-fat/streptozocin (STZ)-induced diabetic nephropathy. The results showed that mice in whom hesperetin was administered for 4 weeks attenuated the increased fasting blood glucose and impaired glucose tolerance ability that was observed in high-fat/STZ mice. In addition, we found that hesperetin ameliorated the abnormalities of biochemical parameters in serum, liver, and kidney of mice with diabetic nephropathy. Hesperetin also rescued the irregular distortions in glomerular basement membrane and expanded mesangial regions. Moreover, hesperetin repaired the function of podocyte by increasing renal nephrin expression and decreasing renal alpha-smooth muscle actin expression. Furthermore, hesperetin inhibited the expression of transforming growth factor-ß1 (TGF-ß1) and its downstream effectors integrin-linked kinase (ILK) and Akt. In conclusion, our study implies that hesperetin produced protective effects in diabetic nephropathy possibly by suppressing TGF-ß1-ILK-Akt signaling.

No Prophylactic Antibiotic Use for Young Children's Intussusception with Low-risk Infection after Successful Air Enema Reduction.

The Chinese government has issued the policy of promulgating the clinical use of antibacterial drugs since 2011. Prophylactic antibiotic use is a challenging problem among young children with intussusception after successful air enema reduction. There were limited data regarding the clinical value of prophylactic antibiotics for intussusception with low-risk infections. A retrospective non-randomized comparative study was conducted among 188 young children with intussusception after successful air enema reduction between January 1, 2011 and December 30, 2013. Among these children, 51 received prophylactic antibiotics and 137 did not receive antibiotics. Our results showed that there were no significant differences in age, gender, weight, admission period, reduction interval, axillary temperature, leukocytes, neutrophils, lymphocytes, monocytes, mesenteric lymph nodes and complications between groups (P > 0.05). The national policy had significantly improved clinical use of antibiotic for young children with low-risk intussusception (OR < 0.001, P < 0.001). Inpatients days were longer for children used antibiotics than those who did not (median, 27.0 hours vs 21.0 hours, P = 0.003). Prophylactic antibiotics appeared to be of little value after the successful air enema reduction of intussusception in young children with low-risk infection. Policy intervention is effective for antibiotic use in China.

Two Membrane-Anchored Aspartic Proteases Contribute to Pollen and Ovule Development.

Aspartic proteases are a class of proteolytic enzymes with conserved aspartate residues, which are implicated in protein processing, maturation, and degradation. Compared with yeast and animals, plants possess a larger aspartic protease family. However, little is known about most of these enzymes. Here, we characterized two Arabidopsis (Arabidopsis thaliana) putative glycosylphosphatidylinositol (GPI)-anchored aspartic protease genes, A36 and A39, which are highly expressed in pollen and pollen tubes. a36 and a36 a39 mutants display significantly reduced pollen activity. Transmission electron microscopy and terminal-deoxynucleotidyl transferase-mediated nick end labeling assays further revealed that the unviable pollen in a36 a39 may undergo unanticipated apoptosis-like programmed cell death. The degeneration of female gametes also occurred in a36 a39 Aniline Blue staining, scanning electron microscopy, and semi in vitro guidance assays indicated that the micropylar guidance of pollen tubes is significantly compromised in a36 a39 A36 and A39 that were fused with green fluorescent protein are localized to the plasma membrane and display punctate cytosolic localization and colocalize with the GPI-anchored protein COBRA-LIKE10. Furthermore, in a36 a39, the abundance of highly methylesterified homogalacturonans and xyloglucans was increased significantly in the apical pollen tube wall. These results indicate that A36 and A39, two putative GPI-anchored aspartic proteases, play important roles in plant reproduction in Arabidopsis.

Secretory COPII Protein SEC31B Is Required for Pollen Wall Development.

The pollen wall protects pollen grains from abiotic and biotic stresses. During pollen wall development, tapetal cells play a vital role by secreting proteins, signals, and pollen wall material to ensure microspore development. But the regulatory mechanism underlying the secretory pathway of the tapetum is largely unknown. Here, we characterize the essential role of the Arabidopsis (Arabidopsis thaliana) COPII protein SECRETORY31B (SEC31B) in pollen wall development and the secretory activity of tapetal cells. The sporophyte-controlled atsec31b mutant exhibits severe pollen and seed abortion. Transmission electron microscopy observation indicates that pollen exine formation in the atsec31b mutant is disrupted significantly. AtSEC31B is a functional COPII protein revealed by endoplasmic reticulum (ER) exit site localization, interaction with AtSEC13A, and retarded ER-Golgi protein trafficking in the atsec31b mutant. A genetic tapetum-specific rescue assay indicates that AtSEC31B functions primarily in the tapetum. Moreover, deletion of AtSEC31B interrupted the formation of the ER-derived tapetosome and altered the location of the ATP-BINDING CASSETTE TRANSPORTER9 protein in the tapetum. Therefore, this work demonstrates that AtSEC31B plays a vital role in pollen wall development by regulating the secretory pathway of the tapetal cells.

Reducing Antibiotic Use for Young Children with Intussusception following Successful Air Enema Reduction.

China introduced a new policy regarding the management of antibiotic use. We evaluated the reasonableness of antibiotic use among children suffering from intussusception before and after policy. A retrospective study was conducted involving 234 young children with intussusception who were treated between January 1, 2011 and December 30, 2013. Demographics and detailed antibiotics regimens were collected. χ2 test was used to evaluate differences between the phase I (preintervention, n = 68) and phase II (postintervention, n = 166). We determined that the overall antibiotic use rate following successful air enema reduction was 41% (97/234), which decreased from 99% (67/68) in phase I to 18% (30/166) in phase II. In phase I, prophylactic antibiotic usage reached up to 84% (56/67). The quantity of aztreonam for injection accounted for 63% (45/71), and cefamandole nafate for injection accounted for 25% (18/71). In phases II, prophylactic antibiotic usage were reduced to 13% (4/30). The quantity of aztreonam for injection was decreased to 12% (4/33) and cefamandole nafate for injection was 3% (1/33). Antibiotics' options were more diverse. In conclusion, policy intervention was effective in addressing some aspects of antibacterial drug usage among young children with intussusception. However, excessive drug use remains a public health problem. The guidelines for the antibiotic management of intussusception for children must be established in China.

Intensity-dependent effects of repetitive anodal transcranial direct current stimulation on learning and memory in a rat model of Alzheimer's disease.

Single-session anodal transcranial direct current stimulation (tDCS) can improve the learning-memory function of patients with Alzheimer's disease (AD). After-effects of tDCS can be more significant if the stimulation is repeated regularly in a period. Here the behavioral and the histologic effects of the repetitive anodal tDCS on a rat model of AD were investigated. Sprague-Dawley rats were divided into 6 groups, the sham group, the ß-amyloid (Aß) group, the Aß+20µA tDCS group, the Aß+60µA tDCS group, the Aß+100µA tDCS group and the Aß+200µA tDCS group. Bilateral hippocampus of the rats in the Aß group and the Aß+tDCS groups were lesioned by Aß1-40 to produce AD models. One day after drug injection, repetitive anodal tDCS (10 sessions in two weeks, 20min per session) was applied to the frontal cortex of the rats in the tDCS groups, while sham stimulation was applied to the Aß group and the sham group. The spatial learning and memory capability of the rats were tested by Morris water maze. Bielschowsky's silver staining, Nissl's staining, choline acetyltransferase (ChAT) and glial-fibrillary-acidic protein (GFAP) immunohistochemistry of the hippocampus were conducted for histologic analysis. Results show in the Morris water maze task, rats in the Aß+100µA and the Aß+200µA tDCS groups had shorter escape latency and larger number of crossings on the platform. Significant histologic differences were observed in the Aß+100µA and the Aß+200µA tDCS groups compared to the Aß group. The behavioral and the histological experiments indicate that the proposed repetitive anodal tDCS treatment can protect spatial learning and memory dysfunction of Aß1-40-lesioned AD rats.

[Anti-tumor effect of ethanol extracts from Thymus quinquecostatus Celak on human leukemia cell line].

OBJECTIVE: To screen the anti-tumor fraction of ethanol extracts from Thymus quinquecostatus Celak and investigate its anti-tumor effect on human leukemia cell line. METHODS: Ethyl acetate, n-butanol and acetone fractions were separated from the ethanol extracts of wild Thymus quinquecostatus Celak. Growth inhibiting effects of these extracts on human leukemia cell lines K562 and HL-60 were determined by live cell counting and cell growth curve analysis. The possible anti-tumor mechanism was studied by morphological analysis with norcantharidin as a positive control. RESULTS: Ethyl acetate fraction could significantly inhibit the proliferations of K562 and HL-60 cells, and the inhibiting effect depended on the concentration of ethyl acetate fraction. Ethyl acetate fraction could induce apoptosis of K562 and HL-60 cells. The n-butanol and acetone fractions had no significant inhibiting effect on K562 and HL-60 cells. CONCLUSION: Ethyl acetate fraction is the major anti-tumor fraction in ethanol extracts from Thymus quinquecostatus Celak.