[Reflections on good manufacturing practice and quality control system of personalized traditional Chinese medicine preparations].

Personalized traditional Chinese medicine(TCM) preparations have entered a stage of rapid development. The key to the healthy development of this industry is to establish a sound manufacturing standard and quality control system. This paper analyzed the characteristics of personalized TCM preparations and drew reference from the quality management standards in the production of commissioned decoctions and oral pastes, on the basis of which the production quality management scheme and cautions for the safe production of personalized TCM preparations was put forward with consideration to various problems that may exist and occur in the production of such preparations. It provided references for formulating the production standards and quality management system of personalized TCM preparations. The production standards and quality control system should develop with the times. In the future, modern technologies such as big data and artificial intelligence should be employed to achieve the automated and intelligent production and establish a sound quality traceability system, online control strategy, and safety management mode of personalized TCM preparations, which will ensure the healthy development of this industry under requirement of good manufacturing practice(GMP).

[Application of microwave vacuum drying with process management in extract drying of personalized traditional Chinese medicine preparations].

Extracts are important intermediates in the production of traditional Chinese medicines preparations. The drying effect of extracts will directly affect the subsequent production process and the quality of the preparation. To meet the requirements of high drug loading, short time consumption, and simple production process of personalized traditional Chinese medicine preparations, this study explored the application of multi-program microwave vacuum drying process in the extract drying of personalized traditional Chinese medicine preparations. The influencing factors of microwave vacuum drying process were investigated for 5 excipients and 40 prescriptions. Taking the feasibility of drying, drying rate, drying time, and dried extract status as indicators, this study investigated the feeding requirements of microwave vacuum drying. With the dried extract status as the evaluation indicator, the three drying programs(A, B, and C) were compared to obtain the optimal drying condition. The experimental results showed that the optimal feeding conditions for microwave vacuum drying were material layer thickness of 2 cm and C program(a total of 7 drying processes), which solved the problem of easy scorching in microwave drying with process management. Furthermore, the preset moisture content of the dried extract in microwave drying should be 4%-5%, so that the dried extract of traditional Chinese medicine preparation had uniform quality, complete drying, and no scorching. This study lays a foundation for the application of microwave drying in the production of traditional Chinese medicine preparations, promoting the high-quality development of personalized traditional Chinese medicine preparations.

ThermomiR-377-3p-induced suppression of Cirbp expression is required for effective elimination of cancer cells and cancer stem-like cells by hyperthermia.

BACKGROUND: In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold­inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). METHODS: CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. RESULTS: Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)­like population. Moreover, hyperthermia substantially improved the sensitivity of radiation­resistant NPC cells and CSC­like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti­tumor­killing activity of hyperthermia against NPC cells and CSC­like cells, whereas ectopic expression of Cirbp compromised tumor­killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC­like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. CONCLUSION: Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.

Exploring aromatic components differences and composition regularity of 5 kinds of these 4 aroma types Phoenix Dancong tea based on GC-MS.

Different aromatic components do indeed give different tea flavors. There is still little research on whether there is a certain regularity in the combination and content of aromatic components in different aroma types of Phoenix Dancong (PDC) tea. This potential regularity may be a key factor in unraveling the relationship between reproduction and evolution in PDC tea. Here, the 5 kinds of these 4 aroma types PDC tea (Zhuye, Tuofu, Jianghuaxiang, Juduo, Yashixiang) were used as research materials in this study, the headspace solid-phase microextraction combined with gas chromatography-mass spectrometry was used to analyze the aromatic components of these PDC teas. The results showed a total of 36 aromatic components identified in this study. When conducting cluster analysis, it was found that similarity degree arrangement sequence of 5 PDC teas was Juduo, Tuofu, Yashixiang, Zhuye and Jianghuaxiang. Among these aromatic components, the 7,9-Di-tert-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione, the 2-Cyclopenten-1-one, 3-methyl-2-(2-pentenyl)-,(Z)-, the 2,4-Di-tert-butylphenol, the 3,7-dimethyl-1,5,7-Octatrien-3-ol, and the 2-Furanmethanol,5-ethenyltetrahydro-.alpha.,.alpha.,5-trimethyl-,cis- are common to 5 PDC teas. This study aims to elucidate the similarities in the aromatic components of 5 PDC teas, revealing the major aroma-endowed substances of various aroma, and providing theoretical reference for further exploring the relationship between aroma type discrimination, variety selection, and evolution of PDC teas.

A codelivery system loaded with PDL1-siRNA and sorafenib enhances the therapeutic effect of sorafenib on hepatocellular carcinoma via TAT-poly-SS-lysine modified chitosan.

Sorafenib (SF) is a first-line drug for the treatment of hepatocellular carcinoma (HCC) in clinical practice. However, acquired drug resistance tremendously limits the clinical efficacy of sorafenib in treating HCC, which has attracted great attention. PDL1 plays a crucial role in the drug resistance of HCC. Here, a codelivery system based on poly-SS-lysine modified chitosan (TAT-C-SS-P) was established and was applied to deliver sorafenib and PDL1-siRNA for synergetic HCC therapy. The successful synthesis of TAT-C-SS-P was confirmed by 1H NMR. Additionally, sorafenib and PDL1-siRNA were successfully transported into the cells as the decreased expression of VEGF and PD-L1 by administrated with TAT-C-SS-P@SF@ PDL1-siRNA. Simultaneously, the expression of pro-apoptosis proteins cyt-c and Bax was prominently augmented, whereas the expression of anti-apoptosis protein Bcl-2 was decreased. The reduced expression of PDL1 resulted in the downregulation of P-GP and MRP1, which contributed to more sorafenib aggregation in tumor cells. Moreover, TAT-C-SS-P@PDL1-siRNA@SF efficiently promotes apoptosis of HepG2-SI cells, as the apoptosis rate rised to 73 %. A sorafenib-insensitive model was established to evaluate in vivo antitumor effect of TAT-C-SS-P@PDL1-siRNA@SF. TAT-C-SS-P@PDL1-siRNA@SF showed a tumor inhibition rate of 90.2 ± 3.5 % and no significant decrease in body weight. Taken together, our study provided compelling evidence that TAT-C-SS-P@PDL1-siRNA@SF has great potential application in the treatment of HCC clinically.

Erzhiwan Ameliorates Restraint Stress- and Monobenzone-Induced Depigmentation in Mice by Inhibiting Macrophage Migration Inhibitory Factor and 8-Hydroxy-2-Deoxyguanosine.

Purpose: Vitiligo is an autoimmune disease that results in the loss of epidermal melanocytes. The treatments for patients with vitiligo remain lacking. Erzhiwan (EZW), a traditional Chinese Medicine composed of Ligustri Lucidi Fructus and Ecliptae Herba, was used to ameliorate depigmentation since ancient China. This study aims to investigate the effect of EZW on vitiligo-related depigmentation. Methods: A vitiligo-related depigmentation mouse model was induced by monobenzone and restraint stress. The experimental depigmentation mice were treated with EZW. Histological observation of skin was conducted. Cutaneous oxidative damage and inflammation were determined. A network pharmacology analysis was carried out. Results: EZW reduced depigmentation score (p<0.01), cutaneous inflammatory infiltration (p<0.01), and CD8α-positive expression (p<0.01), and increased cutaneous melanin content in experimental depigmentation mice. EZW reduced stress reaction in experimental depigmentation mice (p<0.01). EZW inhibited 8-hydroxy-2-deoxyguanosine (8-OHdG)-related DNA oxidative damage in the skin (p<0.05, p<0.01). In addition, EZW reduced cutaneous macrophage migration inhibitory factor (MIF)-CD74-NF-κB signaling (p<0.01). The network pharmacology analysis demonstrated that EZW regulated necroptosis, apoptosis, and FoxO signaling pathways in vitiligo. An in vitro experiment showed that the main ingredient of EZW, specnuezhenide, protected against monobenzone and MIF-induced cell death in HaCaT cells (p<0.01). Conclusion: EZW ameliorates restraint stress- and monobenzone-induced depigmentation via the inhibition of MIF and 8-OHdG signaling. The findings provide a data basis of an utilization of EZW in vitiligo.

Analyzing the molecular mechanism of xuefuzhuyu decoction in the treatment of pulmonary hypertension with network pharmacology and bioinformatics and verifying molecular docking.

BACKGROUND: XueFuZhuYu (XFZY), a typical Chinese herbal formula, has remarkable clinical effects for treating Pulmonary Hypertension (PH) with unclear mechanisms. Our research involved the utilization of network pharmacology to explore the traditional Chinese herbal monomers and their related targets within XFZY for PH treatment. Furthermore, molecular docking verification was performed. METHODS: The XFZY's primary active compounds, along with their corresponding targets, were both obtained from the TCMSP, ChEMBL, and UniProt databases. The target proteins relevant to PH were sifted through OMIM, GeneCards and TTD databases. The common "XFZY-PH" targets were evaluated with Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses with the assistance of R software. The Protein-Protein Interaction (PPI) network and compound-target-pathway network were constructed and a systematic analysis of network parameters was performed by the powerful software Cytoscape. Molecular docking was employed for assessing and verifying the interactions between the core targets and the top Chinese herbal monomer. RESULTS: The screening included 297 targets of active compounds in XFZY and 8400 PH-related targets. DO analysis of the above common 268 targets indicated that the treatment of the diseases by XFZY is mediated by genes related to Chronic Obstructive Pulmonary Disease (COPD), Obstructive Lung Disease (OLD), ischemia, and myocardial infarction. The findings from molecular docking indicated that the binding energies of 57 ligand-receptor pairs in PH and 20 ligand-receptor pairs in COPD-PH were lower than -7kJ•mol-1. CONCLUSIONS: This study indicates that XFZY is a promising option within traditional Chinese medicine compound preparation for combating PH, particularly in cases associated with COPD. Our demonstration of the specific molecular mechanism of XFZY anti-PH and its effective active ingredients provides a theoretical basis for better clinical application of the compound.

The Efficacy and Safety of Shashen-Maidong Decoction Combined with Western Medicine in the Treatment of Omicron Infected Individuals Over 85 Years Old: A Retrospective Study.

Background: During the Omicron variant outbreak of COVID-19 (2022-2023), Chinese healthcare institutions combined traditional Chinese medicine (TCM) with Western medical practices to treat COVID-19 patients, especially the elderly. The efficacy and safety of this approach, especially for individuals aged over 85, need further investigation. Methods: In this retrospective study, a cohort of 62 patients aged over 85 years, diagnosed with COVID-19 infection, was examined. Among them, 34 patients were administered Shashen-Maidong decoction in conjunction with Western medicine (SMD+WM group), while the remaining 28 patients received only Western medicine (WM group). Comparative analysis was conducted between the two groups, encompassing parameters such as the duration for the nucleic acid test to turn negative, length of intensive care unit (ICU) stay, mortality rate, utilization of high-flow nasal cannula oxygen (HFNC), occurrence of endo-tracheal intubation, frequency of recurrent respiratory infections within three months, and various laboratory indicators. Results: There were no significant differences observed between the two groups in terms of the duration for the nucleic acid test to turn negative, the length of ICU stay, mortality rate, utilization of HFNC, performance of endo-tracheal intubation, or the frequency of recurrent respiratory infections within three months (P > 0.05). However, in comparison to the WM group, the SMD+WM group exhibited notably lower growth rates in white blood cell (WBC) and neutrophil (NEUT) values. Additionally, the SMD+WM group demonstrated superior improvement in cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP) values. Conclusion: In contrast to the administration of Western medicine alone, the combined use of Shashen-Maidong decoction with Western medicine significantly suppresses the increase in WBC count, particularly in NEUT levels, in elderly patients diagnosed with COVID-19. Moreover, this combined treatment exhibits a protective effect on cardiac function and demonstrates a relatively safe profile.

Influence of Extrudate-Based Textural Properties on Pellet Molding Quality.

As the precursor of pellets, the extrudate has a direct impact on the molding quality of the pellets. Therefore, the correlation between the surface roughness of the extrudates and the molding quality of pellets with pure microcrystalline cellulose (MCC) formulations and those containing traditional Chinese medicine (TCM) formulations was explored. MCC was used as a pelleting agent, mixer torque rheometry (MTR) was used to guide the optimal dosage of the wetting agent, and TCM extracts (drug loadings of 20% to 40%) were selected as model drugs to prepare the extrudates and pellets under the same extrusion spheronization process conditions. The surface roughness and texture parameters of extrudates were analyzed via a microscope and texture analyzer, respectively, and the quality of pellets was evaluated. The extrudate roughness of the pure MCC prescription decreased and then increased with increasing water addition, while the extrudate roughness of the prescription containing TCM extracts tended to increase and then decrease. The addition of water affected the extrudate properties, with TCM extract molecules filling gaps in the MCC structure, leading to rough surfaces. The extrudate roughness of the TCM prescriptions was significantly greater than that of the pure MCC prescriptions at optimal water addition levels, resulting in ideal pellets.

[Characteristics of Cadmium Concentration and Transport of Pueraria thornsonii in Farmland with Different Cadmium Pollution Degrees].

This study aimed to elucidate the cadmium (Cd) concentration and transport characteristics of Pueraria thornsonii in farmland with different Cd pollution degrees, so as to provide a reference basis for phytoremediation of Cd-contaminated farmland. The multi-point experiments in farmland with different Cd pollution degrees[ω(Cd) 0.32-38.08 mg·kg-1] were conducted, and the biomass (dry weight), Cd content, accumulation, concentration, and transport of Cd in P. thornsonii tissues under the main growing period were assessed. According to the results, for P. thornsonii, the tuber dry weight ranged from 5.04 to 11.98 t·hm-2, biomass ranged from 13.21 to 29.07 t·hm-2, and Cd accumulation ranged from 15.74 to 106.03 g·hm-2in the study area. The pattern of Cd uptake by P. thornsonii showed that the main vine>leaf>lateral branches>basal part of sti>tuber. The Cd content in P. thornsonii tissues considerably increased with soil Cd content (P<0.05), whereas the biomass decreased significantly (P<0.05). The Cd concentration and transport factor of aboveground parts in P. thornsonii showed a trend of initially falling, then increasing and decreasing again, whereas the Cd enrichment and transport coefficient of tubers gradually decreased. Correlation analysis revealed that the amount of Cd in the soil was a major predictor of Cd accumulation in P. thornsonii. Under light to moderate Cd contamination, the commercial portion of P. thornsonii (arrowroot)[ω(Cd) 0.03-0.22 mg·kg-1] was less than the standard limit for medicinal plants (≤ 0.30 mg·kg-1). In P. thornsonii from moderately contaminated areas, the Cd concentration and transport factor of aboveground parts were 2.43-7.97 and 3.02-9.81, respectively. This indicates that P. thornsonii is a prospective plant ideal for remediating Cd-contaminated soil because of its high capacity to transfer and enrich Cd.

PD-1 blockade and radiotherapy combination for advanced Epstein-Barr virus-associated intrahepatic cholangiocarcinoma: a case report and literature review.

Advanced intrahepatic cholangiocarcinoma (ICC) is a rare malignant tumor of biliary epithelial cells, known for its extremely unfavorable prognosis. In the absence of intervention, patients typically survive for less than 5 months. Current guidelines from the Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN), and European Society for Medical Oncology (ESMO) recommend chemotherapy-based systemic therapy as the standard treatment for advanced ICC. However, the first-line regimen, consisting of gemcitabine in combination with cisplatin, generally results in a median survival of approximately one year, which is considered suboptimal. Significant progress has been made in radiotherapy techniques, molecular diagnostics, and tumor immune microenvironments. The integration of immune and radiation therapies has revolutionized treatment strategies for cholangiocarcinoma. Moreover, combined therapeutic regimens have shown promising results in improving survival rates among patients with advanced ICC. In this study, we present a case report of a 70-year-old male patient diagnosed with stage IV ICC, featuring metastases to the retroperitoneal, left adrenal, and left supraclavicular lymph nodes. The patient exhibited a high tumor mutational load, significant microsatellite instability, and hyper-expression of PD-L1 (90%), along with positive Epstein-Barr virus-encoded RNA (EBER). Pembrolizumab, a programmed cell death 1 (PD-1) inhibitor, was administered in conjunction with radiotherapy. As a result, considerable shrinkage and inactivation of the primary foci were observed, accompanied by the disappearance of metastases. Ultimately, the patient achieved complete remission and maintained progression-free survival for 41 months following the initial treatment. To the best of our knowledge, this represents the longest case of complete remission using a combination of immunotherapy and radiotherapy as a first-line regimen for the high tumor mutational load, microsatellite instability, and PD-L1 expression (90%) subtype of Epstein-Barr virus-associated ICC (EBVaICC). These findings suggest that the combination of PD-1 inhibitors with radiotherapy may serve as a promising therapeutic strategy for treating this particular cancer subtype.

Vascular wall microenvironment: exosomes secreted by adventitial fibroblasts induced vascular calcification.

Vascular calcification often occurs in patients with chronic renal failure (CRF), which significantly increases the incidence of cardiovascular events in CRF patients. Our previous studies identified the crosstalk between the endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and the paracrine effect of VSMCs, which regulate the calcification of VSMCs. Herein, we aim to investigate the effects of exosomes secreted by high phosphorus (HPi) -induced adventitial fibroblasts (AFs) on the calcification of VSMCs and the underlying mechanism, which will further elucidate the important role of AFs in high phosphorus vascular wall microenvironment. The conditioned medium of HPi-induced AFs promotes the calcification of VSMCs, which is partially abrogated by GW4869, a blocker of exosomes biogenesis or release. Exosomes secreted by high phosphorus-induced AFs (AFsHPi-Exos) show similar effects on VSMCs. miR-21-5p is enriched in AFsHPi-Exos, and miR-21-5p enhances osteoblast-like differentiation of VSMCs by downregulating cysteine-rich motor neuron 1 (Crim1) expression. AFsHPi-Exos and exosomes secreted by AFs with overexpression of miR-21-5p (AFsmiR21M-Exos) significantly accelerate vascular calcification in CRF mice. In general, AFsHPi-Exos promote the calcification of VSMCs and vascular calcification by delivering miR-21-5p to VSMCs and subsequently inhibiting the expression of Crim1. Combined with our previous studies, the present experiment supports the theory of vascular wall microenvironment.

Solanum americanum genome-assisted discovery of immune receptors that detect potato late blight pathogen effectors.

Potato (Solanum tuberosum) and tomato (Solanum lycopersicon) crops suffer severe losses to late blight caused by the oomycete pathogen Phytophthora infestans. Solanum americanum, a relative of potato and tomato, is globally distributed and most accessions are highly blight resistant. We generated high-quality reference genomes of four S. americanum accessions, resequenced 52 accessions, and defined a pan-NLRome of S. americanum immune receptor genes. We further screened for variation in recognition of 315P. infestans RXLR effectors in 52 S. americanum accessions. Using these genomic and phenotypic data, we cloned three NLR-encoding genes, Rpi-amr4, R02860 and R04373, that recognize cognate P. infestans RXLR effectors PITG_22825 (AVRamr4), PITG_02860 and PITG_04373. These genomic resources and methodologies will support efforts to engineer potatoes with durable late blight resistance and can be applied to diseases of other crops.

Functional diversification of a wild potato immune receptor at its center of origin.

Plant cell surface pattern recognition receptors (PRRs) and intracellular immune receptors cooperate to provide immunity to microbial infection. Both receptor families have coevolved at an accelerated rate, but the evolution and diversification of PRRs is poorly understood. We have isolated potato surface receptor Pep-13 receptor unit (PERU) that senses Pep-13, a conserved immunogenic peptide pattern from plant pathogenic Phytophthora species. PERU, a leucine-rich repeat receptor kinase, is a bona fide PRR that binds Pep-13 and enhances immunity to Phytophthora infestans infection. Diversification in ligand binding specificities of PERU can be traced to sympatric wild tuber-bearing Solanum populations in the Central Andes. Our study reveals the evolution of cell surface immune receptor alleles in wild potato populations that recognize ligand variants not recognized by others.

Correlation between Polyphenol Contents and Antioxidant Activities in Different Echinacea Purpurea Varieties.

OBJECTIVE: Polyphenols are complex compounds containing multiple phenolic hydroxyl groups. They are widely distributed in plants and have antioxidant activities. Whether the antioxidant activities of the cultivated varieties of Echinacea are similar to or better than those of the wild ones and the relationship between the accumulation of polyphenols and their antioxidant activities are still not clear. METHODS: Folin-Ciocalteu method, high performance liquid chromatography (HPLC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, ferric ion reducing antioxidant power (FRAP) assay, 2,2'-azino-bis(3-ethylbenzothiazoline-6)-sulfonic acid (ABTS) radical scavenging assay, and Fe2+ chelating ability assay were used, respectively, to detect the total polyphenols and 5 kinds of caffeic acid derivatives (chicoric acid, caffeic acid, caftaric acid, chlorogenic acid, and 1,5-dicaffeoylquinic acid) in the roots, stems, leaves, and flowers, and the antioxidant activities of 3 varieties of Echinacea: E. purpurea L., cultivar E. purpurea 'Aloha', and E. purpurea 'White Swan'. RESULTS: E. purpurea L. had the highest contents of total polyphenols, 5 caffeic acid derivatives and antioxidant activities, followed by E. purpurea 'White Swan' and E. purpurea 'Aloha', respectively. E. purpurea 'White Swan' had the strongest ability to remove the DPPH, ABTS•+ and free radicals, and to chelate Fe2+; E. purpurea L. had the strongest ability to reduce FRAP. The correlation analyses revealed that the contents of total polyphenols and caffeic acid derivatives of E. purpurea L. and E. purpurea 'White Swan' were correlated with their antioxidant activities. CONCLUSION: E. purpurea L. was the most appropriate material for the development of medicinal plants. E. purpurea 'White Swan' could be used as a substitute for E. purpurea L. in terms of its antioxidant activity.

Co-exposure to iron, copper, zinc, selenium and titanium is associated with the prevention of gastric precancerous lesions.

Gastric cancer is the third leading cause of cancer death, and gastric precancerous lesions (GPLs) are an important stage in the transformation of normal gastric mucosa to gastric cancer. Matched for age and sex, a total of 316 subjects were eventually included from our prospective observation population (including 1007 patients with GPLs and 762 normal controls), and a questionnaire survey was conducted. In total, 10 plasma elements (iron, copper, zinc, selenium, rubidium, strontium, titanium, aluminum, vanadium and arsenic) were measured by applying inductively coupled plasma‒mass spectrometry (ICP‒MS). A multivariate conditional logistic regression model and Bayesian kernel logistic regression model (BKMR) were used to analyze the association between plasma element concentrations and GPLs. In the multimetal model, plasma titanium concentrations were significantly and positively associated with the prevalence of GPLs, with a fourth-quartile OR of 11.56 ([95% CI]: [2.78-48.13]). Plasma selenium and copper were negatively correlated with GPLs, with the highest quartiles of selenium and copper having an OR of 0.03 ([95% CI]: [0.01-0.15]; P < 0.001) and 0.24 ([95% CI]: [0.07-0.82]), respectively. In the BKMR model, there was a significant negative combined correlation of five metals on GPLs: iron, copper, zinc, selenium, and titanium. The results of this study showed that plasma concentrations of selenium and copper were negatively correlated with GPLs, while plasma concentrations of titanium were positively correlated with GPLs, and the combined action of the five elements was negatively correlated with GPLs.

[Comparison of catalytic functions and expression patterns of two pinene synthases from Wurfbainia villosa].

Wurfbainia villosa fruit is rich in volatile terpenoids, among which pinene is one of the main components and has anti-inflammatory, antibacterial, anti-tumor, and other pharmacological activities. This research group found that W. villosa fruits were rich in α-pinene by GC-MS, and terpene synthase(WvTPS63, formerly known as AvTPS1) with ß-pinene as the main product was cloned and identified, but α-pinene synthase had not been identified. In this study, based on the genome data of W. villosa, we screened and found WvTPS66 with highly similar sequences to WvTPS63, identified enzyme functions of WvTPS66 in vitro, and performed a comparative analysis of sequence, catalytic function, expression pattern, and promoter with WvTPS63. Multiple sequence alignment showed that the amino acid sequences of WvTPS63 and WvTPS66 were highly similar and the conservative motif of terpene synthase was almost identical. In vitro enzymatic experiments on catalytic functions showed that both could produce pinene, and the main product of WvTPS63 was ß-pinene, while that of WvTPS66 was α-pinene. Expression pattern analysis showed that WvTS63 was highly expressed in flowers, WvTPS66 was expressed in the whole plant, and the highest expression level was found in the pericarp, which indicated that it might be mainly responsible for the synthesis of α-pinene in fruits. In addition, promoter analysis revealed the presence of multiple regulatory elements related to stress response in the promoter regions of both genes. The findings of this study can provide a reference for the functional study of terpene synthase genes and new genetic elements for pinene biosynthesis.

Antitumor mechanism of kangliu pill on gliomas in mice through PI3K-Akt signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Gliomas are common malignant intracranial tumors that have worse prognosis and pose a serious threat to human health. The Kangliu pill (KLP) is an innovative herbal compound from Xuanwu Hospital of Capital Medical University that has been clinically used for the treatment of gliomas for more than 40 years, and is one of the few drugs for primary treatment of this disorder. But the fundamental molecular mechanisms and pathways of KLP are not clear. AIM OF THE STUDY: To investigate the therapeutic mechanism of KLP in the treatment of gliomas. MATERIALS AND METHODS: An in situ xenograft model of red fluorescent protein-labeled human glioma cell line (U87-RFP) in BALB/c-nu mouse was established, and the therapeutic effect of KLP on gliomas was assessed by tumor weights and fluorescence areas. A quantitative proteomics approach using tandem mass tags combined with liquid chromatography-tandem mass spectrometry was performed to explore differentially expressed proteins (DEPs) in glioma tissues, and bioinformatics analyses including Gene Ontology analysis, pathway analysis, and network analysis were performed to analyze the proteins involved in the network therapeutic mechanisms responsible for key metabolic pathways. Cytological experiments corroborated the above analysis results. RESULTS: Network pharmacology approach screened 246 bioactive compounds contained in KLP, targeting 724 proteins and 173 potential targets of KLP for glioma treatment. The important targets obtained after visualizing the PPI network were AKT1, INS, GAPDH, SRC, TP53, etc. The KEGG enrichment results showed that 9 proteins were related to cancer, including Pathways in cancer, PI3K/AKT signaling pathway, etc. KLP had antitumor activity in gliomas, which reduced tumor weights and fluorescence areas. A number of DEPs possibly associated with gliomas were identified through quantitative proteomic techniques. Among these DEPs, 50 (25 upregulated and 25 downregulated) were identified that might be associated with KLP action. Bioinformatics showed that these 50 DEPs were mainly focused on focal adhesion, extracellular matrix (ECM)-receptor interactions, and the PI3K-Akt signaling pathway. Cytological experiments revealed that KLP significantly inhibited the proliferation and promoted apoptosis of U87-MG human glioma cells, and its mechanism was through the inhibition of PI3K/AKT signaling pathway. CONCLUSION: Therapeutic effect of KLP was regulation of multiple pathways in the treatment of gliomas. In specific, it interacts through the PI3K-Akt signaling pathway. This work may contribute proteomic insights for further research on the medical treatment of glioma using KLP.

Efficacy confirmation of Scutellaria baicalensis Georgi in the treatment of periodontitis via topical administration and active ingredients screening.

ETHNOPHARMACOLOGICAL RELEVANCE: Periodontal disease is a complex inflammatory disease that seriously affects peoples' lives. Scutellaria radix (SR) is traditionally used as a folk medicine to clear away heat and dampness, purge fire and detoxification. Although it has been extensively used as a medicinal plant to treat a variety of inflammatory illnesses, the efficacy and active ingredient for topical administration in the treatment of periodontitis is unknown. AIM OF STUDY: The aim of this study was to screen and validate the active ingredients in SR for the prevention and treatment of periodontitis. MATERIALS AND METHODS: A ligature-induced periodontitis in rats was used to investigate the efficacy of topical administration of SR for the treatment of periodontitis, and the active fraction was screened after separation of the aqueous extract of SR into fractions of different polarities using a lipopolysaccharide (LPS)-induced cell model. Chromatographic fingerprints were established for 18 batches of SR by high performance liquid chromatography. The potential active components were screened using spectral effect relationship analysis and the target cell extraction method. RESULTS: SR has good efficacy in the topical treatment of periodontitis, according to animal experiments. Five active ingredients were screened out and their anti-inflammatory activity was confirmed in vitro. CONCLUSION: The main active compounds in the treatment of periodontitis via topical administration of SR were found and this provides an experimental basis for further studies on the pharmacodynamic material basis of SR, as well as reference for the comprehensive evaluation of SR quality and the development of substitute resources.

Research strategies and applications of functional metabolomics in anti-depressive mechanisms of traditional Chinese medicine / 药学学报

Depression is a common emotional disorder that seriously affects people's life and health all over the world. The pathogenesis of depression is complex, and traditional Chinese medicine (TCM) for antidepressants has a good therapeutic effect because of its multi-component, multi-pathway, and multi-target action mode. At present, the anti-depressive mechanism of TCM has not been fully clarified, but it is clear that depression is closely related to metabolic health. Therefore, in order to further explore the anti-depressive mechanism of TCM, this paper proposes research strategies on the anti-depressive mechanism of TCM based on functional metabolomics from the perspective of metabolism, the potential biomarkers of depression are analyzed with the help of multi-omics combined analysis technology, and the functional molecules of TCM for antidepressant are studied. Molecular biology techniques are used to accurately capture the molecular interactions between biomarkers of depression and functional compounds, which identify effective drug targets and further elucidate the biochemical functions and related mechanisms involved in depression metabolic disorders. This paper systematically reviews the research strategies and applications of functional metabolomics in the anti-depressive mechanisms of TCM, expounds on the core value of functional metabolomics, and summarizes the current research status and hot issues of TCM for antidepressants in recent years, providing new methods and new ideas for the study of mechanisms of TCM with the help of functional metabolomics.