OBJECTIVES: To observe the evolution of intrahepatic macrophage polarization in mice with liver fibrosis induced by iron overload. METHODS: Thirty-two C57BL/6 mice (6-8 weeks) were randomized into control group (n=8) and liver fibrosis model group (n=24) induced by aidly intraperitoneal injection of iron dextran. At the 3rd, 5th, and 7th weeks of modeling, 8 mice in the model group were sacrificed for observing liver fibrosis using Masson, Sirius Red and immunohistochemical staining and detecting serum levels of ALT, AST and the levels of serum iron, ferritin, liver total Fe and ferrous Fe. iNOS⁺/F4/80⁺ cells and CD206⁺/F4/80⁺ cells were detected by double immunofluorescence assay to observe the proportion and distribution of M1 and M2 macrophages. The hepatic expressions of Arg-1, iNOS, IL-6, IL-10, and TNF‑α proteins were detected using Western blotting or ELISA, and the expression of CD206 mRNA was detected using RT-PCR. RESULTS: The mice in the model group showed gradual increase of fibrous tissue hyperplasia in the portal area over time, structural destruction of the hepatic lobules and formation of pseudolobules. With the passage of time during modeling, the rat models showed significantly increased hepatic expressions of α-SMA and COL-1, elevated serum levels of ALT, AST, Fe, ferritin, and increased liver total Fe and ferrous Fe levels. The expressions of M1 polarization markers IL-6, TNF‑α, and iNOS all increased with time and reached their peak levels at the 3rd week; The expressions of M2 polarization markers (IL-10 and Arg-1 proteins and CD206 mRNA) significantly increased in the 3rd week and but decreased in the 5th and 7th weeks. CONCLUSIONS Iron overload promotes M1 polarization of macrophages in mice. Liver fibrosis in the early stage promotes M2 polarization of macrophages but negatively regulate M2 polarization at later stages.
Animals ; Mice ; Mice, Inbred C57BL ; Iron Overload/pathology* ; Macrophages/metabolism* ; Male ; Liver Cirrhosis/etiology* ; Nitric Oxide Synthase Type II/metabolism* ; Interleukin-10/metabolism* ; Liver/pathology* ; Interleukin-6/metabolism* ; Mannose Receptor ; Tumor Necrosis Factor-alpha/metabolism* ; Mannose-Binding Lectins/metabolism* ; Arginase

AIM To analyze the component composition of Xeriga-4 Powder,and to determine the contents of phellodendrine,chlorogenic acid,gardenoside,berberine,rutin and curcumin.METHODS The high performance liquid chromatography-Q-exactive orbitrap mass spectrometry(HPLC-Q-Exactive-MS)qualitative analysis was performed on a 35℃thermostatic Agilent ZORBAX SB-Aq column(4.6 mm×150 mm,5 μm),with the mobile phase comprising of methanol-0.1%formic acid flowing at 0.35 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning.High performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS)quantitative analysis was performed on a 35℃thermostatic Shim-pack GIST-HP C18 column(2.1 mm×100 mm,3 μm),with the mobile phase comprising of methanol-0.1%formic acid flowing at 0.25 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS Total 65 constituents were identified,containing 19 alkaloids,13 organic acids,13 flavonoids,7 curcumins,6 iridoids,4 fatty acids,2 aldehydes,and 1 amino acid.Six constituents showed good linear relationships within their own ranges(r≥0.999 1),whose average recoveries were 96.44%-102.37%with the RSDs of 2.05%-3.74%.CONCLUSION This study can provide a reference for the quality control for Xieriga-4 Powder.

Humans ; Vascular Stiffness ; Coal Mining ; Occupational Diseases/epidemiology* ; Risk Factors ; Coal ; Miners

Aim To express and purify recombinant hCGH-CTP fusion protein in high-density suspension culture of Chinese hamster ovary cells (CHO-S), and to verify the lipid accumulation effect of rhCGH-CTP on 3T3-L1 mature adipocytes. Methods The recombinant protein expression vector (pcDNA3. 1-rhCGH-CTP) was constructed, achieved by fusing the human glycoprotein hormone beta 5/alpha 2 cDNA with CTP Linker. The expression plasmid was transiently transfected into the suspended CHO-S to express rhCGH-CTP protein and then purified, and the protein biological activity was verified. Intervention with 3T3-L1 mature adipocyte cells for 24 h was performed to detect the changes of intracellular triglyceride (TG) level. Results Western blot results showed that rhCGH-CTP protein was successfully expressed in CHO-S cells, and the yield was up to 715. 4 mg • L~ . The secreted protein was purified by AKTA pure system with higher purity that was up to 90% as identified by SDS-PAGE. In addition, the intracellular cAMP content of mature adipocytes with high expression of TSHR gene significantly increased after intervention with different concentrations of rhCGH-CTP protein by ELISA kit, indicating that rhCGH-CTP protein had biological activity. Oil red 0 staining showed that compared with the control group, the lipid content of mature adipocytes in the intervention groups with different concentrations of rhCGH-CTP protein significantly decreased (P < 0. 05) . Conclusions The rhCGH-CTP protein has been successfully expressed and purified with biological activity, and effectively reduce TG. This research provides an important theoretical basis for further revealing the physiological role of CGH protein and its potential application in clinical practice.

Decoction is the most commonly used dosage form in the clinical treatment of traditional Chinese medicine (TCM). During boiling, the violent movement of various active ingredients in TCM creates molecular forces such as hydrogen bonding, π-π stacking, hydrophobic interactions and electrostatic interactions, which results in the formation of self-assembled aggregates in decoction (SADs), including particles, gels, fibers, etc. It was found that SADs widely existed in decoction with biological activities superior to both effective monomers and their physical mixtures, providing a new idea to reveal the pharmacodynamic material basis of Chinese herbal medicine from the perspective of component interactions-phase structure. Recently, SADs have become a novel focus of research in TCM. This paper reviewed their relevant studies in recent years and found some issues to be concerned in the research, such as the polydispersity of decoction system, instability of active ingredient interactions during boiling, uncertainty of the aggregates self-assembly rules, and stability, purity, yield of the products. In this regard, some solutions and new ideas were presented for the integrated development and clinical application of SADs.

Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.

Objective To evaluate the effect of photo-activated disinfection(PAD)as a kind of adjuvant treatment on moderate to severe chronic periodontitis.Methods 21 patients with the chronic periodontitis(totally 218 selected sites)were randomly enrolled and divided into group A(minocycline hydrochloride),group B(PAD),group C(PAD + minocycline hydrochloride),and group D(no adjunctive therapy)for the adjunctive treatment after receiving the scaling and root planing(SRP).Periodontal indexs as probing depth(PD),bleeding on probing(BOP)and clinical attachment loss(CAL)were examined at the baseline,6 and 12 weeks after the treatment.Meanwhile,periodontal pathogens as Porphyromonas gingivalis(Pg)and Tannerella forsythia(Tf)from subgingival plaque of group A,B and C were detected by Real-time PCR.Results Compared with the baseline,the periodontal inflammations of all groups were improved signiffcantly at 6 and 12 weeks after the treatment(P<0.001),and group A,group B and group C were better than group D(P<0.001),group C was better than group A(P<0.001);Furthermore,the concentration of Pg and Tf was decreased significantly(P<0.001),and there was no difference among the three groups with adjunctive therapy.Conclussion As the adjunctive treatment of SRP,PAD could achieve the same and even better effect than minocycline hydrochloride ointment.

Ion mobility spectroscopy(IMS)has many advantages such as fast detection speed,high sensitivity,and portability,and thus plays an important role in on-site detection of chemical agents,explosives,drugs,environmental pollutants,and other pollutants.As a key component of IMS,the ion number density and temporal width of the injected ion packets directly determine the IMS detection sensitivity and resolution.In yhis study,the dual-parallel-grid structure of Tyndall-Powell gate(TPG),which could effectively isolate the electric fields within the ionization region,gate region,and drift region,was utilized to develop a dual effect TPG gating method for simultaneously enhancing the mobility discrimination reduction and ion packet temporal width compression,thereby improving the IMS performance.A TPG-IMS platform was thus built up and the effects of parameters such as gate opening pulsed width,gate penetration voltage,and ion injection voltage on the sensitivity and resolving power of IMS were systematically investigated using the dual-effect TPG gating method.The results demonstrated that,when detecting diethyl phosphate(DEP)and diethyl methylphosphate(DEMP)mixture using the dual effect TPG gating method,the peak currents of(DEP)2H+and(DEP·DEMP)H+ions with low K0 values were increased by 18 and 45 times respectively,while maintaining a high resolution of about 90.The limits of detection for DEP and DEMP were decreased from 4 ppb(10-9)to 235 ppt(10-12)and from 5 ppb to 156 ppt,respectively.This gating method only regulated the potential of the TPG grid adjacent to the drift region,without changing the structure of the ion mobility tube,making it convenient to apply on existing commercial instruments.

Combined with clinical practice,it is found that the clinical manifestations of multiple system atrophy are complex and diverse,but the pathogenesis of traditional Chinese medicine can be summarized as kidney deficiency and empty marrow as the core,and yang deficiency as an important factor.Tongyuan therapy can communicate with the brain and kidney by unblocking and regulating the governor vessel,so that the kidney essence can nourish the brain marrow,stimulate the yang qi of the whole body,nourish the original spirit and the spirit of the zang-fu organs,and nourish the muscles of the limbs.Make much of use conception vessels and abdominal front Mu point to tonify the kidney and cultivate the vital qi,strengthen the spleen and replenish qi,so that the prenatal and postnatal essence can be regulated simultaneously.Clinically,it can be based on the combination of acupuncture and Chinese medicine,which has guiding significance for the treatment of multiple system atrophy.