Fu-Fang-Jin-Qian-Cao herbal granules protect against the calcium oxalate-induced renal EMT by inhibiting the TGF-ß/smad pathway.

CONTEXT: Nephrolithiasis is a major public health problem worldwide and Fu-Fang-Jin-Qian-Cao granules (FFJQC) is a traditional Chinese herbal formula that is used to treat nephrolithiasis. The main component of nephrolithiasis is calcium oxalate (CaOx) and the epithelial-mesenchymal transition (EMT) shown to play a crucial role in CaOx-induced kidney injury. However, the mechanism underlying the therapeutic effect of FFJQC on the CaOx-induced renal EMT is unknown. OBJECTIVE: This study explores the therapeutic benefits and mechanism of FFJQC in oxalate-induced kidney injury. MATERIALS AND METHODS: 60 male C57BL/6 mice were used in this experiment and divided into 6 groups. A mouse kidney stone model was created by intraperitoneal injection of glyoxylate at a dose of 100 mg/kg for 6 days. The standardized FFJQC was used to treat mouse crystal kidney injury by gavage at 1.35 and 2.7 g/kg, respectively. Western blotting and immunostaining for E-cadherin, cytokeratin 18 (CK18), vimentin, smooth muscle α-actin (α-SMA) and transforming growth factor ß (TGF-ß)/Smad pathway were conducted on renal tissues. RESULTS: Following CaOx-induced kidney injury, the levels of E-cadherin and CK18 in kidney decreased, while vimentin and α-SMA levels increased. The FFJQC treatment increased the levels of E-cadherin and CK18 and decreased vimentin and α-SMA levels in varying degrees. What's more, the FFJQC reduced the expression of CaOx-induced fibrosis marker collagen II. CONCLUSION: FFJQC alleviated the CaOx-induced renal EMT and fibrosis by regulating TGF-ß/smad pathway. Therefore, the FFJQC is an important traditional Chinese medicine for the treatment of CaOx-induced renal injury and fibrosis.

Clinical Evaluation of Coronary In-Stent Restenosis Using Dual-Source Computed Tomography.

OBJECTIVE: To explore the feasibility of dual-source computed tomography (DSCT) in the evaluation of coronary in-stent restenosis (ISR) by comparing the results of DSCT and selective coronary angiography (CAG). METHODS: In-stent restenosis examination results from DSCT were compared with those obtained using CAG. RESULTS: Among 173 stents studied, 156 yielded good quality images when evaluated with DSCT. CAG identified 38 ISR cases, while DSCT found 40. Among the 112 stents in the study with an inner diameter ≥3.0 mm, CAG identified 29 as having ISR, while DSCT reported the same finding in 30; among the 44 stents with inner diameter <3.0 mm, CAG identified ISR in 9, while DSCT found ISR in 10. CONCLUSIONS: Stent inner diameter is a key factor influencing the imaging of the stent lumen. DSCT demonstrated a higher negative predictive value in ISR assessment, suggesting that it could replace CAG for assessing the patency of stents with a larger inner diameter (≥3 mm).

Expression of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in renal cell carcinoma.

BACKGROUND: Matrix metalloproteinases (MMPs) are one of the major classes of proteolytic enzymes involved in tumor invasion and metastasis and are inhibited by naturally occurring tissue inhibitors of metalloproteinases (TIMPs). {AU Query: Please verify that corrections made to previous sentence did not alter intended meaning}. In this study, we examined the expression of MMP-2, MMP-9, membrane-type 1 (MT1)-MMP, TIMP-1, and TIMP-2 in renal tissue samples of renal cell cancer and examined the correlation between their expression and clinicopathological parameters. METHODS: Renal tissue samples from 76 patients with renal cell carcinoma were available for this study. To determine the expression of MMP-2, MMP-9, MT1-MMP, TIMP-1, and TIMP-2, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out on tumor and normal tissues. RESULTS: Mean MMP-2, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 mRNA expression in the renal cell carcinomas was significantly higher than in the normal renal tissue (P <0.05). The RT-PCR data of MMP-2, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 did not show any significant correlation with tumor type or pathologic grade of renal cell carcinoma. MMP-2, MMP-9 and MT1-MMP mRNA expression increased significantly with the TNM stage of the tumor. CONCLUSIONS: Mean MMP-2, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 mRNA expression in the renal cell carcinomas was significantly higher than in the normal renal tissue.

Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace.

OBJECTIVE: This study investigated trends in the study of phytochemical treatment of post-traumatic stress disorder (PTSD). METHODS: The Web of Science database (2007-2022) was searched using the search terms "phytochemicals" and "PTSD," and relevant literature was compiled. Network clustering co-occurrence analysis and qualitative narrative review were conducted. RESULTS: Three hundred and one articles were included in the analysis of published research, which has surged since 2015 with nearly half of all relevant articles coming from North America. The category is dominated by neuroscience and neurology, with two journals, Addictive Behaviors and Drug and Alcohol Dependence, publishing the greatest number of papers on these topics. Most studies focused on psychedelic intervention for PTSD. Three timelines show an "ebb and flow" phenomenon between "substance use/marijuana abuse" and "psychedelic medicine/medicinal cannabis." Other phytochemicals account for a small proportion of the research and focus on topics like neurosteroid turnover, serotonin levels, and brain-derived neurotrophic factor expression. CONCLUSION: Research on phytochemicals and PTSD is unevenly distributed across countries/regions, disciplines, and journals. Since 2015, the research paradigm shifted to constitute the mainstream of psychedelic research thus far, leading to the exploration of botanical active ingredients and molecular mechanisms. Other studies focus on anti-oxidative stress and anti-inflammation. Please cite this article as: Gao B, Qu YC, Cai MY, Zhang YY, Lu HT, Li HX, Tang YX, Shen H. Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace. J Integr Med. 2023; 21(4):385-396.

Corrigendum: Phyllanthus niruri L. exerts protective effects against the calcium oxalate-induced renal injury via ellgic acid.

[This corrects the article DOI: 10.3389/fphar.2022.891788.].

Influence of atherosclerosis on the molecular expression of the TRPC1/BK signal complex in the aortic smooth muscles of mice.

Atherosclerosis (AS) is one a disease that seriously endangers human health. Previous studies have demonstrated that transient receptor potential channel-1 (TRPC1)/large conductance Ca2+ activated K+ channel (BK) signal complex is widely distributed in arteries. Therefore, it was hypothesized that TRPC1-BK signal complex may be a new target for the treatment of AS-related diseases. Apolipoprotein E-/- (ApoE-/-) mice were used to establish an atherosclerotic animal model in the present study, and the association between AS and the TRPC1-BK signal complex was examined. The present study aimed to compare the differences in the expression levels of mRNAs and proteins of the TRPC1-BK signal complex expressed in the aortic vascular smooth muscle tissue, between mice with AS and control mice. There were 10 mice in each group. Reverse transcription PCR, western blotting and immunohistochemistry were used to detect the differences in the mRNA and protein expression levels of TRPC1, BKα (the α subunit of BK) and BKß1 (the ß1 subunit of BK). The mRNA expression level of TRPC1 in AS model mice was significantly higher compared with that in the control group (P<0.05). However, the mRNA expression levels of BKα and BKß1 were lower compared with those in the controls (both P<0.01). The mice in the ApoE-/- group successfully developed AS. In this group, the protein expression level of TRPC1 was significantly higher than that in the control group (P<0.01), while the protein expression levels of BKα and BKß1 were lower compared with those in the control group (P<0.01 and P<0.05, respectively). Collectively, it was identified that the protein and mRNA expression levels of the TRPC1/BK signal complex in the aortic vascular smooth muscle tissue could be influenced by the development of AS in mice. Hence, the TRPC1/BK signal complex may be a potential therapeutic target for the prevention and treatment of AS-related complications in the future.

Phyllanthus Niruri L. Exerts Protective Effects Against the Calcium Oxalate-Induced Renal Injury via Ellgic Acid.

Background: Urolithiasis or kidney stones is a common and frequently occurring renal disease; calcium oxalate (CaOx) crystals are responsible for 80% of urolithiasis cases. Phyllanthus niruri L. (PN) has been used to treat urolithiasis. This study aimed to determine the potential protective effects and molecular mechanism of PN on calcium oxalate-induced renal injury. Methods: Microarray data sets were generated from the calcium oxalate-induced renal injury model of HK-2 cells and potential disease-related targets were identified. Network pharmacology was employed to identify drug-related targets of PN and construct the active ingredient-target network. Finally, the putative therapeutic targets and active ingredients of PN were verified in vitro and in vivo. Results: A total of 20 active ingredients in PN, 2,428 drug-related targets, and 127 disease-related targets were identified. According to network pharmacology analysis, HMGCS1, SQLE, and SCD were identified as predicted therapeutic target and ellagic acid (EA) was identified as the active ingredient by molecular docking analysis. The increased expression of SQLE, SCD, and HMGCS1 due to calcium oxalate-induced renal injury in HK-2 cells was found to be significantly inhibited by EA. Immunohistochemical in mice also showed that the levels of SQLE, SCD, and HMGCS1 were remarkably restored after EA treatment. Conclusion: EA is the active ingredient in PN responsible for its protective effects against CaOx-induced renal injury. SQLE, SCD, and HMGCS1 are putative therapeutic targets of EA.

Lung macrophages are involved in lung injury secondary to repetitive diving.

This study aimed to establish an animal model of decompression-induced lung injury (DILI) secondary to repetitive diving in mice and explore the role of macrophages in DILI and the protective effects of high-concentration hydrogen (HCH) on DILI. Mice were divided into three groups: control group, DILI group, and HCH group. Mice were exposed to hyperbaric air at 600 kPa for 60 min once daily for consecutive 3 d and then experienced decompression. In HCH group, mice were administered with HCH (66.7% hydrogen and 33.3% oxygen) for 60 min after each hyperbaric exposure. Pulmonary function tests were done 6 h after decompression; the blood was harvested for cell counting; the lung tissues were harvested for the detection of inflammatory cytokines, hematoxylin and eosin (HE) staining, and immunohistochemistry; western blotting and polymerase chain reaction (PCR) were done for the detection of markers for M1 and M2 macrophages. Our results showed that bubbles formed after decompression and repeated hyperbaric exposures significantly reduced the total lung volume and functional residual volume. Moreover, repetitive diving dramatically increased proinflammatory factors and increased the markers of both M1 and M2 macrophages. HCH inhalation improved lung function to a certain extent, and significantly reduced the pro-inflammatory factors. These effects were related to the reduction of M1 macrophages as well as the increase in M2 macrophages. This study indicates that repetitive diving damages lung function and activates lung macrophages, resulting in lung inflammation. HCH inhalation after each diving may be a promising strategy for the prevention of DILI.

Highly efficient formal synthesis of cephalotaxine, using the Stevens rearrangement--acid lactonization sequence as a key transformation.

Cephalotaxine (1), the major alkaloid isolated from Cephalotaxus species, has attracted considerable attention due to the promising antitumor activity of several of its derivatives and its unique structural features. Herein we describe a highly efficient formal synthesis of 1 employing the [2,3]-Stevens rearrangement-acid lactonization sequence as a key transformation from readily available (3,4-dimethoxyphenyl)acetic acid, methyl prolinate, and allyl bromide.

Protective effects of methane-rich saline on mice with allergic asthma by inhibiting inflammatory response, oxidative stress and apoptosis.

BACKGROUND: Asthma is a common cause of breathing difficulty in children and adults, and is characterized by chronic airway inflammation that is poorly controlled by available treatments. This results in severe disability and applies a huge burden to the public health system. Methane has been demonstrated to function as a therapeutic agent in many diseases. The aim of the present study was to explore the effect of methane-rich saline (MRS) on the pathophysiology of a mouse model of asthma and its underlying mechanism. METHODS: A murine model of ovalbumin (OVA)-induced allergic asthma was applied in this study. Mice were divided into three groups: a control group, an OVA group, and OVA-induced asthmatic mice treated with MRS as the third group. Lung resistance index (RI) and dynamic compliance (Cdyn) were measured to determine airway hyper-responsiveness (AHR). Haematoxylin and eosin (H&E) staining was performed and scored to show histopathological changes. Cell counts of bronchoalveolar lavage fluid (BALF) were recorded. Cytokines interleukin (IL)-4, IL-5, IL-13, tumor necrosis factor α (TNF-α), and C-X-C motif chemokine ligand 15 (CXCL15) from BALF and serum were measured by enzyme-linked immunosorbent assay (ELISA). The oxidative stress indexes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), myeloperoxidase (MPO), and 8-hydroxydeoxyguanosine (8-OHdG), were determined using commercial kits. Apoptosis was evaluated by western blot, quantitative real-time polymerase chain reaction (qRT-PCR), and biochemical examination. RESULTS: MRS administration reversed the OVA-induced AHR, attenuated the pathological inflammatory infiltration, and decreased the cytokines IL-4, IL-5, IL-13, TNF-α, and CXCL15 in serum and BALF. Moreover, following MRS administration, the oxidative stress was alleviated as indicated by decreased MDA, MPO, and 8-OHdG, and elevated SOD and GSH. In addition, MRS exhibited an anti-apoptotic effect in this model, protecting epithelial cells from damage. CONCLUSIONS: Methane improves pulmonary function and decreases infiltrative inflammatory cells in the allergic asthmatic mouse model. This may be associated with its anti-inflammatory, antioxidative, and anti-apoptotic properties.

[Polymorphism of TPH gene T3792A locus in Han ethnic group of north China].

OBJECTIVE: To investigate the polymorphism of the TPH gene T3792A locus in Han ethnic group of north China and its application value in forensic science. METHODS: The polymorphism of T3792A locus of the TPH gene was analyzed by the ASPCR of blood samples from 173 unrelated individuals of north Chinese Han population. RESULTS: The distribution of the T3792A locus polymorphism of the TPH gene in Han ethnic group of north China followed the Hardy-Weinberg law, with the allele A and T gene frequency of 0.486 and 0.514, respectively. CONCLUSION: The TPH gene T3792A locus shows a very good genetic polymorphism, and may be applied to individual identification and paternity testing.

Effects of hydrogen on polarization of macrophages and microglia in a stroke model.

It has been confirmed that inflammation plays an important role in the pathogenesis of ischemic stroke. The polarization of microglia as an important participant in the inflammation following stroke is also found to be involved in stroke. This study aimed to investigate the effects of hydrogen gas on the polarization of macrophages/microglia in vitro. Raw264.7 cells were treated with lipopolysaccharides and then exposed to hydrogen. The microglia were treated with the supernatant from oxygen and glucose deprivation-treated neurons and then exposed to hydrogen. The phenotypes of Raw 264.7 cells and microglia were determined by flow cytometry, and cell morphology was observed. Results showed lipopolysaccharides significantly increased the M1 macrophages, and the supernatant from oxygen and glucose deprivation-treated neurons dramatically elevated the proportion of M1 microglia, but both treatments had little influence on the M2 cells. In addition, hydrogen treatment significantly inhibited the increase in M1 cells, but had no influence on M2 ones. Our findings suggest that the neuroprotection of hydrogen may be related to its regulation of microglia in the nervous system after stroke.

[Distribution of tryptophan hydroxylase gene-T457C locus polymorphism in Han ethnic group in northern China].

OBJECTIVE: To study the distribution of the tryptophan hydroxylase (TPH) gene-T457C locus polymorphism in Han ethnic group in northern China and to find its applicable value in forensic science. METHODS: Genomic DNA samples, extracted from 180 unrelated individuals in northern Chinese Han population, were analyzed by PCR-RFLP. RESULTS: The discrimination power (DP) value and the power of exclusion (PE) value of the TPH gene-T457C locus were 0.624 and 0.187, respectively. The allele frequency showed significant difference from that of French people (P=0.04). CONCLUSION: Polymorphism of the TPH gene-T457C locus could show ethnic and regional differences. It has a potential to be used in forensic science.

Tab2, a novel recombinant polypeptide tag offering sensitive and specific protein detection and reliable affinity purification.

The detection and purification of proteins are often time-consuming and frequently involve complicated protocols. The addition of a peptide tag to recombinant proteins can make this process more efficient. Many of the commonly used tags, such as Flagtrade mark, Myc, HA and V5 are recognized by specific monoclonal antibodies and therefore, allow immunoaffinity-based purification. Enhancing the current scope of flexibility in using diverse peptide tags, we report here the development of a novel, short polypeptide tag (Tab2) for detection and purification of recombinant proteins. The Tab2 epitope corresponds to the NH2-terminal seven amino acid residues of human TGFalpha. A monoclonal anti-Tab2 antibody was raised and characterized. To investigate the potential of this peptide sequence as a novel tag for recombinant proteins, we expressed several different recombinant proteins containing this tag in E. coli, baculovirus, and mammalian cells. The data presented demonstrates the Tab2 tag-anti-Tab2 antibody combination is a reliable tool enabling specific Western blot detection, FACS analysis, and immunoprecipitation as well as non-denaturing protein affinity purification.

Differential inhibition of inducible T cell cytokine secretion by potent iron chelators.

Effector functions and proliferation of T helper (Th) cells are influenced by cytokines in the environment. Th1 cells respond to a synergistic effect of interleukin-12 (IL-12) and interleukin-18 (IL-18) to secrete interferon-gamma (IFN-gamma). In contrast, Th2 cells respond to interleukin-4 (IL-4) to secrete IL-4, interleukin-13 (IL-13), interleukin-5 (IL-5), and interleukin-10 (IL-10). The authors were interested in identifying nonpeptide inhibitors of the Th1 response selective for the IL-12/IL-18-mediated secretion of IFN-gamma while leaving the IL-4-mediated Th2 cytokine secretion relatively intact. The authors established a screening protocol using human peripheral blood mononuclear cells (PBMCs) and identified the hydrazino anthranilate compound 1 as a potent inhibitor of IL-12/IL-18-mediated IFN-gamma secretion from CD3(+) cells with an IC(50) around 200 nM. The inhibitor was specific because it had virtually no effect on IL-4-mediated IL-13 release from the same population of cells. Further work established that compound 1 was a potent intracellular iron chelator that inhibited both IL-12/IL-18- and IL-4-mediated T cell proliferation. Iron chelation affects multiple cellular pathways in T cells. Thus, the IL-12/IL-18-mediated proliferation and IFN-gamma secretion are very sensitive to intracellular iron concentration. However, the IL-4-mediated IL-13 secretion does not correlate with proliferation and is partially resistant to potent iron chelation.

The biology and physiology of somatostatin receptors.

The biology and therapeutic application of somatostatin and its receptors are reviewed. The focus is on recent literature and patents, especially with regard to the specific function of each somatostatin receptor subtype. Detailed mechanisms mediating the effects of somatostatin and its analogues remain to be elucidated. Nevertheless, progress is being made towards a clear picture of the cellular signalling and physiological changes regulated by somatostatin and its receptors.