Network Pharmacology and Molecular Modeling Techniques in Unraveling the Underlying Mechanism of Citri Reticulatae Pericarpium aganist Type 2 Diabetic Osteoporosis.

Type 2 diabetic osteoporosis (T2DOP) is a common complication in diabetic patients that seriously affects their health and quality of life. The pathogenesis of T2DOP is complex, and there are no targeted governance means in modern medicine. Citri Reticulatae Pericarpium (CRP) is a traditional Chinese medicine that has a long history and has been used in the treatment of osteoporosis diseases. However, the molecular mechanism for the CRP treatment of T2DOP is not clear. Therefore, this study aimed to explore the underlying mechanisms of CRP for the treatment of T2DOP by using network pharmacology and molecular modeling techniques. By retrieving multiple databases, we obtained 5 bioactive compounds and 63 common targets of bioactive compounds with T2DOP, and identified AKT 1, TP 53, JUN, BCL 2, MAPK 1, NFKB 1, and ESR 1 as the core targets of their PPI network. Enrichment analysis revealed that these targets were mainly enriched in the estrogen signaling pathway, TNF signaling pathway, and AGE-RAGE signaling pathway in diabetics, which were mainly related to oxidative stress and hormonal regulation. Molecular docking and molecular dynamics simulations have shown the excellent binding effect of the bioactive compounds of CRP and the core targets. These findings reveal that CRP may ameliorate T2DOP through multiple multicomponent and multitarget pathways.

Efficacy and safety comparison of infrared laser moxibustion and traditional moxibustion in knee osteoarthritis: study protocol for a Zelen-design randomized controlled non-inferiority clinical trial.

BACKGROUND: Knee osteoarthritis (KOA) is the most common chronic degenerative joint disease and places a substantial burden on the public health resources in China. The purpose of this study is to preliminarily evaluate whether infrared laser moxibustion (ILM) is non-inferior to traditional moxibustion (TM) in the treatment of KOA. MATERIALS AND METHODS: In the designed Zelen-design randomized controlled non-inferiority clinical trial, a total of 74 patients with KOA will be randomly allocated to one of two interventions: ILM treatment or TM treatment. All participants will receive a 6-week treatment and a follow-up 4 weeks after treatment. The primary outcomes will be the mean change in pain scores on the numeric rating scale (NRS) measured at baseline and the end of last treatment at week 6. The secondary outcomes will be the pain scores on the NRS from weeks 1 to 5 after the start of treatment and the changes from baseline to endpoints (weeks 6 and 10) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), SF-36, knee circumference, and 6-min walking test. In addition, safety assessment will be performed throughout the trial. CONCLUSION: The results of our study will help determine whether a 6-week treatment with ILM is non-inferior to TM in patients with KOA, therefore providing evidence to verify if ILM can become a safer alternative for TM in clinical applications in the future. TRIAL REGISTRATION: Clinical Trial Registration Platform (ChiCTR2200065264); Pre-results. Registered on 1 November 2022.

Amino acid regulated citrus pectin-based emulsion stability mediated by pH.

BACKGROUND: Citrus residuals are rich in nutrients like pectin, essential oil, and amino acids, which are wasted in the food industry. Moreover, citrus components often coexist with amino acids during emulsion preparation and application. RESULTS: Adding glutamic or arginine after emulsification resulted in a stable emulsion compared with adding them before emulsification. Adding glycine before or after emulsification had no effect on the emulsion stability. Emulsion stability was improved by adding glutamic acid at pH 6. Ionic interaction and hydrogen bonding were the main forms of bonding. The rhamnogalacturonan II domain was the potential binding site for the amino acids. CONCLUSIONS: The emulsions prepared by adding acidic amino acids or basic amino acids after emulsification were stable relative to those in which the amino acids were added before emulsification. However, the order in which neutral amino acids were added did not affect the emulsion stability after storage for 7 days. With an increase in the pH level, droplet size increased and emulsion stability decreased. All the results could be attributed to changes in the structure and properties of citrus pectin, as well as the interaction between citrus pectin and amino acids. This study may expand the application of citrus-derived emulsions in the food industry. © 2023 Society of Chemical Industry.

Case report: Acute oxalate nephropathy due to traditional medicinal herbs.

Acute oxalate nephropathy (AON), defined as the association between acute kidney injury (AKI) and the deposition of oxalate crystals in the renal parenchyma, is a rare complication of hyperoxaluria. We report a rare case of AON in an adult due to medicinal herbs intake leading to crystal-induced AKI. We recommend that a thorough medication history including the use of medicinal herbs, should be obtained for all patients with a rapid loss of kidney function, especially in the absence of known risk factors for AKI. The use of medicinal herbs with unknown oxalate contents would increase the risk of AON and should be avoided.

Is it justified to assess the resectability of pancreatic cancer combined with biological and conditional factors?

Background: This study aimed to investigate the biological and conditional resectability criteria for pancreatic ductal adenocarcinoma (PDAC), as proposed by the International Association of Pancreatology (IAP), as well as to identify the role of biological and conditional factors in assessing the resectability of PDAC. Methods: The clinical data of PDAC patients who underwent upfront open/laparoscopic pancreaticoduodenectomy (PD/LPD) or distal pancreatectomy (DP/LDP) at our hospital between January 2013 to June 2019 were retrospectively analyzed. Patients who were diagnosed with anatomically resectable PDAC, as defined by National Comprehensive Cancer Network (NCCN) guideline of PDAC guideline Version 1.2020, were enrolled. Based on IAP-criteria, these patients were divided into two groups, including IAP-resectable (IAP-R) and IAP Borderline Resectable (IAP-BR). Clinical characteristics and outcomes were compared between the two groups. In order to identify independent biological and conditional predictors of recurrence-free survival (RFS) and overall survival (OS) of enrolled patients, an analysis was performed through the use of a Cox proportional-hazard model. Results: Overall, 97 patients were included in this study. Among them, 38 patients were IAP-R and 59 patients were IAP-BR. Compared to the IAP-R group, the IAP-BR group had a higher early recurrence rate (62.7% vs. 42.1%; P=0.047), and the median RFS (9.2 vs. 18.3 months, P<0.01) and OS (19.1 vs. 30.6 months, P<0.05) were also significantly worse. Preoperative CA19-9 serum levels that exceeded 500 U/mL and/or an imaging diagnosis of regional lymph nodes metastasis were independently associated with OS and RFS of anatomically resectable PDAC. Conclusions: The prognosis of patients with PDAC that undergo resection can be predicted more accurately by assessing the resectability of pancreatic cancer combined with anatomical and biological factors according to IAP criteria. Whether conditional factors should be included in the resectability criteria needs to be validated by prospective and large cohorts.

Moxibustion may delay the aging process of Wistar rats by regulating intestinal microbiota.

As one of the important treatments of health care and anti-aging in traditional Chinese medicine (TCM), moxibustion has been proved to have the effects of scavenging free radicals, anti-oxidation, reducing inflammatory reaction, regulating immunity and so on. Recent studies have shown that intestinal microbiota affect the process of aging. The relationship between aging, moxibustion and intestinal microbiota is still unclear. In this study, we explored the effects of moxibustion at Guanyuan (RN4) acupoint on intestinal microbiota, short-chain fatty acids and immunological characteristics of young and elder female Wistar rats to explore the relationship between aging, moxibustion and intestinal microbiota. Six 12-week-old female Wistar rats were young group (Y), and twelve 36-week-old female Wistar rats were randomly divided into elder group (C) and moxibustion group (M). The rats in M group were received mild moxibustion at Guanyuan (RN4) acupoint, 20 min/d for 40 days. The rats in Y group and C group were not given any therapeutic intervention. The results showed that moxibustion increased the abundance of intestinal probiotics (mainly Lactobacillus) and the level of short chain fatty acids, the microcirculation blood flow around Guanyuan (RN4) acupoint was also significantly improved in elder rats. In addition, the expression of MyD88, MAPK, TRAF6, NF-κB in intestinal tissue was down-regulated, and the levels of inflammatory cytokines in intestinal were decreased.

Acute myeloid leukemia with cup-like blasts and FLT3-ITD and NPM1 mutations mimics features of acute promyelocytic leukemia: a case of durable remission after sorafenib and low-dose cytarabine.

Some previous researches raised the possibility of a novel acute myeloid leukemia (AML) entity presenting cup-like cytomorphology with mutations of both FLT3 and NPM1 or one of them. However, the clinical implications of this subtype remain unknown. We describe a 63-year-old patient belonging to this distinct AML subtype, who presented similar features of acute promyelocytic leukemia (APL) including nuclear morphology, negative for CD34 and HLA-DR, and abnormal coagulation. He had no response to both arsenic trioxide and CAG regimen (cytarabine, aclarubicin, and G-CSF). Given that the patient carried the FLT3-ITD mutation, we switched to a pilot treatment of FLT3 inhibitor sorafenib combined with low-dose cytarabine (LDAC). To date, the patient achieved durable complete remission over 58 months. These findings suggest that AML with cup-like blasts and FLT3-ITD and NPM1 mutations mimic APL, and the prognosis of this subtype may be improved by sorafenib combined with LDAC.

Expression, purification and structural characterization of resveratrol synthase from Polygonum cuspidatum.

Polygonum cuspidatum, an important medicinal plant in China, is a rich source of resveratrol compounds, and its synthesis related resveratrol synthase (RS) gene is highly expressed in stems. The sequence of the resveratrol synthase was amplified with specific primers. Sequence comparison showed that it was highly homologous to the STSs. The RS gene of Polygonum cuspidatum encodes 389 amino acids and has a theoretical molecular weight of 42.4 kDa, which is called PcRS1. To reveal the molecular basis of the synthesized resveratrol activity of PcRS1, we expressed the recombinant protein of full-length PcRS1 in Escherichia coli, and soluble protein products were produced. The collected products were purified by Ni-NTA chelation chromatography and appeared as a single band on SDS-PAGE. In order to obtain higher purity PcRS1, SEC was used to purify the protein and sharp single peak, and DLS detected that the aggregation state of protein molecules was homogeneous and stable. In order to verify the enzyme activity of the high-purity PcRS1, the reaction product was detected at 303 nm. By predicting the structural information of monomer PcRS1 and PcRS1 ligand complexes, we analyzed the ligand binding pocket and protein surface electrostatic potential of the complex, and compared it with the highly homologous STSs protein structures of the iso-ligand. New structural features of protein evolution are proposed. PcRS1 obtained a more complete configuration and the optimal orientation of the active site residues, thus improving its catalytic capacity in resveratrol synthesis.

Patient-centered developments in colon- and rectal cancer with a multidisciplinary international team: From translational research to national guidelines.

Rarely, scientific developments centered around the patient as a whole are published. Our multidisciplinary group, headed by gastrointestinal surgeons, applied this research philosophy considering the most important aspects of the diseases "colon- and rectal cancer" in the long-term developments. Good expert cooperation/knowledge at the Comprehensive Cancer Center Ulm (CCCU) were applied in several phase III trials for multimodal treatments of primary tumors (MMT) and metastatic diseases (involving nearly 2000 patients and 64 centers), for treatment individualization of MMT and of metastatic disease, for psycho-oncology/quality of life involving the patients' wishes, and for disease prevention. Most of the targets initially were heavily rejected/discussed in the scientific communities, but now have become standards in treatments and national guidelines or are topics in modern translational research protocols involving molecular biology for e.g., "patient centered individualized treatment". In this context we also describe the paths we had to tread in order to realize our new goals, which at the end were highly beneficial for the patients from many points of view. This description is also important for students and young researchers who, with an actual view on our recent developments, might want to know how medical progress was achieved.

Hesperetin inhibits rat coronary constriction by inhibiting Ca(2+) influx and enhancing voltage-gated K(+) channel currents of the myocytes.

Hesperetin (HSP, one of the most common flavonoids in Citrus) has been reported to possess many benificial effects and is indicated for many diseases both as a therapeutic drug and as a supplement. Although its vascular effects have been extensively studied, little is known about its effects and the underlying mechanisms on coronary artery. In the present study, the myogenic effects of HSP were studied with a wire myograph in isolated rat coronary artery (RCA). Molecular probe and the patch clamp technique were used to study effects of HSP on intracellular free Ca(2+) concentration, inward Ca(2+) currents through L-type voltage-gated Ca(2+) channels (LVGC) and outward K(+) currents through voltage-gated K(+) channels (KV). HSP (0.01-0.1mM) concentration-dependently depressed concentration-contraction curves of both KCl and thromboxane receptor agonist 9,11-Dideoxy-9α,11α-methanoepoxy prostaglandin F2α (U46619), and relaxed RCA precontracted by the both vasoconstrictors. The vasospasmolytic effect was more potent in KCl- than in U46619-induced contraction. The vasorelaxation was attenuated by 4-aminopyridine, a specific KV inhibitor, but not affected by NG-nitro-L-arginine methylester ester, indomethacin, glibenclamide, iberiotoxin, BaCl2 or endothelium denudation. At the same concentrations, HSP inhibited extracellular Ca(2+) influx-induced contraction, reduced intracellular free Ca(2+) concentration, inhibited inward Ca(2+) currents through LVGC and increased outward K(+) currents through KV in the vascular smooth muscle cells (VSMCs) freshly isolated from RCA. Collectively, our results show that HSP is vasospasmolytic in RCA and suggest that the vasospasmolysis is mediated by inhibition of LVGC and enhancement of KV currents in RCA VSMCs.

[Binding pancreatic duct to mucosa anastomosis].

OBJECTIVE: To study the feasibility of binding pancreatic duct to mucosa anastomosis (BDM)-a complementary procedure to both binding pancreaticojejunostomy and binding pancreaticogastrostomy. METHODS: (1) Animal experimental study:gastrostomy and jejunostomy were performed on six adult New Zealand rabbits. The gastrostomy and jejunostomy shared a same stent (rubber urethral catheter, silicone tube or plastic infusion tube). Both ends of the stent were placed in gastric and enteric cavity. Purse-string suture was performed around the stent before the jejunum and the stomach were brought together for fixation by few stitches. And to observe whether the purse-string suture around a plastic tube, rubber tube or silicon tube inserted into jejunum and/or stomach can prevent leaking out of the jejunal or gastric content to cause peritonitis. (2) Clinically 7 patients were performed with BDM anastomosis. The procedure was consisted of five steps: preparation of the pancreatic stump;preparation of the jejunum; preparation of the fixing sutures between the pancreatic stump and the jejunum; implementation of the anastomosis; lastly, fixation of the jejunum beside the pancreas stump. Post-operative periodic examination of the blood amylase and the amylase in the abdominal drainage. Pancreatic fistula was classified in to two categories: parenchymal fistula (pancreatic cut surface fistula) and anastomotic leakage. RESULTS: Animal experiment did not show any leakage around the plastic tube or silicon tube inserted into jejunum and(or) stomach. There was no anastomotic leak in all the patients. There was transient increase of amylase in two cases, but the volume of drainage did not exceed 50 ml/d and the recovery of the patients was not affected. CONCLUSIONS: BDM is a simple, safe and easy procedure to perform. It provides to the surgeons with a new option in different situations to achieve the most ideal surgical result.

Studies on the antioxidant and hepatoprotective activities of polysaccharides from Talinum triangulare.

UNLABELLED: ETHNOPHAMACOLOGICAL RELEVANCY: The whole plant of Talinum triangulare (Family: Portulacaceae) is used in variety of diseases including hepatic ailments in Africa and Taiwan of China. AIMS OF THE STUDY: The study was aimed to evaluate the antioxidant and hepatoprotective activity of polysaccharides from T. triangulare (TTP). MATERIALS AND METHODS: The TTP was extracted using boiling water, and removed protein by Sevag method. 40%, 60% and 80% ethanol precipitating TTP (40%, 60%, 80% TTP) were gained by the successive addition of absolute ethanol. The antioxidant activities of 40%, 60%, 80% and crude TTP were evaluated using three different models in vitro, including reducing power, hydroxyl radicals, superoxide anion. To investigate the hepatoprotective potential, mice were treated with crude polysaccharides (50, 100 and 200mg/kg, p.o.) for 7 days. Liver injures were induced by CCl(4) (0.1% in arachis oil, 10mg/kg, i.v.) 1h after the drug administration on day 7. Mice were sacrificed at 24h after the CCl(4) injection. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) in serum, and glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) in liver tissues were measured. Histopathological examinations were carried out to supplement the biochemical results. RESULTS AND CONCLUSIONS: In vitro assays, TTP showed remarkably different degrees of antioxidant activities in dose-dependent manners. The crude TTP demonstrated a relatively strong antioxidant activity, while the 40% TTP showed the strongest antioxidant activity, and the 60% TTP had the weakest antioxidant ability. In vivo assay, pretreatment with TTP had significantly decreased the levels of AST, ALT and MDA against CCl(4) injures, and restored the activities of defense antioxidant substances SOD and GSH towards normalization. These results supported the effect of T. triangulare in fork use with scientific evidence.