GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

Fermented traditional Chinese medicine(TCM) has a long history of medicinal use, such as Sojae Semen Praeparatum, Arisaema Cum Bile, Pinelliae Rhizoma Fermentata, red yeast rice, and Jianqu. Fermentation technology was recorded in the earliest TCM work, Shen Nong's Classic of the Materia Medica. Microorganisms are essential components of the fermentation process. However, the contamination of fermented TCM by toxigenic fungi and mycotoxins due to unstandardized fermentation processes seriously affects the quality of TCM and poses a threat to the life and health of consumers. In this paper, the characteristics, microbial composition, and mycotoxin profile of fermented TCM are systematically summarized to provide a theoretical basis for its quality and safety control.
Fermentation ; Mycotoxins/analysis* ; Drugs, Chinese Herbal/analysis* ; Fungi/classification* ; Bacteria/genetics* ; Drug Contamination ; Medicine, Chinese Traditional

This study investigated the effects of Rehmanniae Radix Praeparata on striatal neuronal apoptosis in rats with attention deficit hyperactivity disorder(ADHD) based on the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X protein(Bax)/caspase-3 signaling pathway. Twenty-four 3-week-old male spontaneously hypertensive rats(SHR) were randomly divided into a model group, a methylphenidate group(2 mg·kg~(-1)·d~(-1)), and a Rehmanniae Radix Praeparata group(2.4 mg·kg~(-1)·d~(-1)). Age-matched male Wistar Kyoto(WKY) rats were used as the normal control group, with 8 rats in each group. The rats were administered by gavage for 28 days. Body weight and food intake were recorded for each group. The open field test and elevated plus maze test were used to assess hyperactivity and impulsive behaviors. Nissl staining was used to detect changes in striatal neurons and Nissl bodies. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) fluorescence staining was used to detect striatal cell apoptosis. Western blot was employed to detect the expression levels of Bcl-2, Bax, and caspase-3 proteins in the striatum. The results showed that compared with the model group, Rehmanniae Radix Praeparata significantly reduced the total movement distance, average movement speed, and central area residence time in the open field test, and significantly reduced the ratio of open arm entries, open arm stay time, and head dipping in the elevated plus maze test. Furthermore, it increased the number of Nissl bodies in striatal neurons, significantly downregulated the apoptosis index, significantly increased Bcl-2 protein expression and the Bcl-2/Bax ratio, and reduced Bax and caspase-3 protein expression. In conclusion, Rehmanniae Radix Praeparata can reduce hyperactivity and impulsive behaviors in ADHD rats. Its mechanism may be related to the regulation of the Bcl-2/Bax/caspase-3 signaling pathway in the striatum, enhancing the anti-apoptotic capacity of striatal neurons.
Animals ; Male ; Apoptosis/drug effects* ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Caspase 3/genetics* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; bcl-2-Associated X Protein/genetics* ; Rehmannia/chemistry* ; Attention Deficit Disorder with Hyperactivity/physiopathology* ; Signal Transduction/drug effects* ; Neurons/cytology* ; Rats, Inbred SHR ; Rats, Inbred WKY ; Humans ; Corpus Striatum/cytology* ; Plant Extracts

Traditional Chinese medicine(TCM), a treasure of the Chinese nation, contains abundant chemical components and demonstrates unique pharmacological activities, showing important values in clinical applications. With profound connotations and broad application prospects, TCM urgently needs us to further explore and conduct systematic research. Puerarin is a small-molecule natural isoflavonoid carbon glycoside extracted from plants of Pueraria. It is also the main active ingredient of Puerariae Lobata Radix, a Chinese herbal medicine with both medicinal and edible values. Puerarin has a variety of pharmacological effects such as blood pressure-lowering, anti-atherosclerosis, anti-ischemia-reperfusion injury, antithrombotic, anti-tumor, anti-inflammatory, liver-protecting, nerve cell-protecting, and intestinal microbiota-regulating effects. It is also an active ingredient that has been widely studied. This article comprehensively reviews the research progress in the pharmacological effects and molecular mechanisms of puerarin over the years, aiming to provide references and theoretical support for the in-depth research and development as well as clinical application of puerarin.
Isoflavones/chemistry* ; Humans ; Animals ; Drugs, Chinese Herbal/chemistry* ; Pueraria/chemistry*

Bufalin(BF)has a significant anti-tumor effect, but its clinical application is severely restricted by its high toxicity and poor water solubility. In this study, Scrophularia ningpoensis polysaccharide(SNP)and ursodeoxycholic acid(UDCA) were synthesized into an SNP-UDCA conjugate. BF was encapsulated to prepare BF/SNP-UDCA nanoparticles(NPs). The amphiphilic compound SNP-UDCA was synthesized via the one-step method, and its structure was characterized by Fourier-transform infrared spectroscopy(FT-IR)and proton nuclear magnetic resonance(~1H-NMR). The preparation process of BF/SNP-UDCA NPs was optimized through single-factor investigations. The encapsulation efficiency and drug-loading capacity of BF/SNP-UDCA NPs were determined by high-performance liquid chromatography(HPLC). The molecular form of BF/SNP-UDCA NPs was characterized by using a transmission electron microscope, X-ray diffraction(XRD), and differential scanning calorimeter(DSC). Additionally, the stability of BF/SNP-UDCA NPs was evaluated. The release behavior of BF/SNP-UDCA NPs at different pH values was determined by dialysis. The in vitro anti-tumor effect of BF/SNP-UDCA NPs was evaluated by MTT cytotoxicity assay, flow cytometry for apoptosis, and cellular uptake. The in vitro liver targeting was evaluated by measuring cellular uptake by laser confocal microscopy. The results demonstrated that the SNP-UDCA conjugate was successfully synthesized through an esterification reaction between SNP and UDCA. The preparation process of BF/SNP-UDCA NPs was as follows: the feed ratio of SNP-UDCA to BF was 2∶1, the ultrasonic time was 30 minutes, and the stirring time was two hours. The prepared BF/SNP-UDCA NPs were spherical in shape, with a particle size of(252.74±6.05)nm, an encapsulation efficiency of 65.00%±2.51%, and a drug-loading capacity of 6.80%±0.44%. The XRD and DSC results indicated that BF was encapsulated within the NPs and existed in a molecular or amorphous state. The short-term stability of BF/SNP-UDCA NPs and stability in DMEM medium are good, and their in vitro release behavior followed the first-order equation and was pH-dependent according to the in vitro experiment. Compared with BF, BF/SNP-UDCA NPs at the same concentration showed significantly stronger cytotoxicity and apoptotic effects on HepG2 cells(P<0.05, P<0.01). The uptake of coumarin 6(C6)/SNP-UDCA NPs in HepG2 cells was time-dependent and higher than that in HeLa cells at the same concentration of C6/SNP-UDCA NPs. Moreover, after treatment with SNP, the uptake of C6/SNP-UDCA NPs in HepG2 cells decreased. In conclusion, the preparation process of BF/SNP-UDCA NPs was simple and feasible. BF/SNP-UDCA NPs could enhance the targeting ability and inhibitory effect of BF on liver cancer cells. This study will provide a foundation for liver-targeting nanoformulations of BF.
Bufanolides/pharmacology* ; Nanoparticles/chemistry* ; Humans ; Drug Carriers/chemistry* ; Ursodeoxycholic Acid/chemistry* ; Antineoplastic Agents/pharmacology* ; Polysaccharides/chemistry* ; Scrophularia/chemistry* ; Liver Neoplasms/physiopathology* ; Hep G2 Cells

OBJECTIVE: To investigate the Wnt signaling pathway and miRNAs mechanism of extracts of Plastrum Testudinis (PT) in the treatment of osteoporosis (OP). METHODS: Thirty female Sprague Dawley rats were randomly divided into 5 groups by random number table method, including sham group, ovariectomized group (OVX), ovariectomized groups treated with high-, medium-, and low-dose PT (160, 80, 40 mg/kg per day, respectively), with 6 rats in each group. Except for the sham group, the other rats underwent bilateral ovariectomy to simulate OP and received PT by oral gavage for 10 consecutive weeks. After treatment, bone mineral density was measured by dual-energy X-ray absorptiometry; bone microstructure was analyzed by micro-computed tomography and hematoxylin and eosin staining; and the expressions of osteogenic differentiation-related factors were detected by immunochemistry, Western blot, and quantitative polymerase chain reaction. In addition, Dickkopf-1 (Dkk-1) was used to inhibit the Wnt signaling pathway in bone marrow mesenchymal stem cells (BMSCs) and miRNA overexpression was used to evaluate the effect of miR-214 on the osteogenic differentiation of BMSCs. Subsequently, PT extract was used to rescue the effects of Dkk-1 and miR-214, and its impacts on the osteogenic differentiation-related factors of BMSCs were evaluated. RESULTS: PT-M and PT-L significantly reduced the weight gain in OVX rats (P<0.05). PT also regulated the bone mass and bone microarchitecture of the femur in OVX rats, and increased the expressions of bone formation-related factors including alkaline phosphatase, bone morphogenetic protein type 2, collagen type I alpha 1, and runt-related transcription factor 2 when compared with the OVX group (P<0.05 or P<0.01). Meanwhile, different doses of PT significantly rescued the inhibition of Wnt signaling pathway-related factors in OVX rats, and increased the mRNA or protein expressions of Wnt3a, β-catenin, glycogen synthase kinase-3β, and low-density lipoprotein receptor-related protein 5 (P<0.05 or P<0.01). PT stimulated the osteogenic differentiation of BMSCs inhibited by Dkk-1 and activated the Wnt signaling pathway. In addition, the expression of miR-214 was decreased in OVX rats (P<0.01), and it was negatively correlated with the osteogenic differentiation of BMSCs (P<0.01). MiR-214 mimic inhibited Wnt signaling pathway in BMSCs (P<0.05 or P<0.01). Conversely, PT effectively counteracted the effect of miR-214 mimic, thereby activating the Wnt signaling pathway and stimulating osteogenic differentiation in BMSCs (P<0.05 or P<0.01). CONCLUSION PT stimulates bone formation in OVX rats through β-catenin-mediated Wnt signaling pathway, which may be related to inhibiting miR-214 in BMSCs.
Animals ; MicroRNAs/genetics* ; Female ; Rats, Sprague-Dawley ; Wnt Signaling Pathway/genetics* ; Osteogenesis/genetics* ; Mesenchymal Stem Cells/cytology* ; Cell Differentiation/drug effects* ; Bone Density/drug effects* ; Ovariectomy ; Osteoporosis/drug therapy* ; beta Catenin/metabolism* ; Rats ; Intercellular Signaling Peptides and Proteins/metabolism* ; Drugs, Chinese Herbal/pharmacology*

Objective To investigate the rate of greater omentum metastasis in gastric cancer(GC). Methods General informations of patients with GC who underwent radical gastrectomy at Shanghai Ruijin Hospital in May 2020 were collected, and their clinicopathological characteristics were analyzed to find risk factors of greater omentum metastasis. Recurrence and survival were also assessed. Results A total of 59 patients with GC were included in the study, of which 2(3.4%) had greater omentum metastasis. One patient presented a pathological stage of pT4aN3bM0 and another ypT4bN1M0. The 3-year overall survival rate of patients in the study was 87.9%. Conclusions The rate of greater omentum metastasis was relatively low, and patients with greater omentum metastasis had an more advanced pathological stage. To further validate this clinical issue, a prospective randomized controlled clinical study should be conducted between radical gastrectomy with omentectomy and omentum-preserving radical gastrectomy.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

AIM To explore the clinical effects of Bufei Huatan Dingchuan Decoction on patients with acute exacerbation of chronic obstructive pulmonary disease of Lung-Kidney Deficiency Pattern.METHODS One hundred and thirty-eight patients were randomly assigned into control group(69 cases)for 4-week intervention of conventional treatment,and observation group(69 cases)for 4-week intervention of both Bufei Huatan Dingchuan Decoction and conventional treatment.The changes in clinical effects,MMP-2,HIF-1α,TGF-β1,Gal-3,IL-6,pulmonary function indices(FVC,PEF,FEV1/FVC),6-minute walk distance,CAT score and TCM syndrome score were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased MMP-2,HIF-1α,TGF-β1,IL-6,Gal-3,CAT score,TCM syndrome score(P＜0.05),increased function indices(except for FVC)(P＜0.05),and prolonged 6-minute walk distance(P＜0.05),especially for the observation group(P＜0.05).CONCLUSION For the patients of Lung-Kidney Deficiency Pattern,Bufei Huatan Dingchuan Decoction can alleviate inflammatory reactions,improve body hypoxia state,regulate lung functions,prevent airway tissue remodeling,promote disease recovery,and enhance clinical effects.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.