Traditional Chinese medicine treats ulcerative colitis by regulating gut microbiota, signaling pathway and cytokine: Future novel method option for pharmacotherapy.

Background: Ulcerative colitis (UC) is a chronic non-specific inflammatory disease with intestinal tract as the main site. The pathogenic of UC has not yet been clarified, and multiple mechanisms can lead to the pathogenesis of UC. Traditional Chinese medicine (TCM) offers an opportunity for UC treatment. TCM has become the preferred treatment for UC with characteristics of multiple targets, multiple pathways and high safety. This review attempted to summarize the characteristics of TCM (compound prescriptions, single Chinese herbs, and active ingredients) for UC treatment and discussed their pathogenesis based on analyzing the UC-related gut microbiota, signaling pathway and cytokine. In order to provide more systematic and diverse reference for TCM in the prevention and treatment of UC, and provide theoretical reference for clinical treatment of UC. Materials and methods: The information was acquired from different databases, including Web of Science, PubMed, CNKI, Wanfang, and VIP databases. We then focused on the recent research progress in UC treatment by TCM. Finally, the deficiencies and future perspectives are proposed. Results: Modern pharmacological studies have shown that the compound prescriptions (strengthening spleen, clearing heat and removing dampness, clearing heat and removing toxin), single Chinese herbs (replenishing Qi, clearing heat, tonifying blood, etc.), and active ingredients (alkaloids, polysaccharides, flavonoids, polyphenols, terpenes, etc.) have an efficiency in UC treatment by regulating gut microbiota, signaling pathway and cytokine. Conclusions: TCM can achieve its purpose of UC prevention and treatment by acting in multiple ways, and TCM deserves further research and development in this field.

Photoactivation Inducing Multifunctional Coupling of Fluorophore for Efficient Tumor Therapy In Situ.

Photoactivatable molecules, with high-precision spatialtemporal control, have largely promoted bioimaging and phototherapy applications of fluorescent dyes. Here, the first photoactivatable sensor (BI) is described that can be triggered by broad excitation light (405-660 nm), which further undergoes intersystem crossing and H-atom transfer processes to forming superoxide anion radicals (O2 -•) and carbon radicals. Particularly, the photoinduced gain of carbon-centered radicals (BI•) allows for radical-radical coupling to afford the combined crosslink product (BI─BI), which would be oxidized in the presence of O2 -• to produce an extended conjugate system with near infrared emission (820 nm). Besides, the photochemically generated product (Cy─BI) possesses ultra-high photothermal conversion efficiency up to 90.9%, which optimized phototherapy potential. What's more, Western Blot assay reveals that both BI and the photoproduct Cy─BI can efficiently inhibit the expression of CHK1, and the irradiation of BI and Cy─BI further induces apoptosis and ultimately enhances the phototherapeutic effects. Thus, the combination of cell cycle block inducing apoptosis, photodynamic therapy and photothermal therapy treatments significantly suppress solid tumor in vivo antitumor efficacy explorations. This is a novel finding in developing photoactivatable molecules, as well as the broad applicability of photoimaging and phototherapy in tumor-related areas.

Four new stilbenes and one new flavonoid with potential antibacterial and anti-SARS-CoV-2 activity from Cajanus cajan.

Four new stilbenes (1-4) and one new flavonoid (5), named cajanines D-H, together with three known stilbenes (6-8) were isolated from the leaves of Cajanus cajan (L.) Millsp. (pigeon pea). The structures of these compounds were elucidated unambiguously on the basis of IR, 1D, and 2D NMR, as well as HRESIMS data. Structurally, stilbenes 1-4 bore an isopentyl side chain, and further hydroxylation of compounds 1-3 generated a greater variety of structural forms. Compound 5 was a flavonoid owning an isopentyl side chain. Besides, antibacterial activity of the isolated compounds against Staphylococcus aureus, Bacillus cereus, and Escherichia coli was studied in vitro. Compounds 1-8 were endowed with profound antibacterial activity. Among them, the MIC values of compounds 4, 6, and 7 against S. aureus were 1.56, 0.78, and 0.78 µg/mL, respectively, among which 6 and 7 had better antibacterial activity than the positive control Vancomycin with the MIC values of 1.56 µg/mL. Additionally, the anti-SARS-CoV-2 main protease activity of all the isolated compounds was evaluated, and it was worth mentioning that the IC50 values of compounds 5-7 were 8.27, 4.65, and 8.30 µM, respectively, being comparable to the positive control Ebselen. Our findings may provide valuable guidance for the application of stilbenes as lead compounds in the future for the development of drugs with antibacterial or anti-COVID-19 activity.

Oridonin impedes breast cancer growth by blocking cells in S phase and inhibiting the PI3K/AKT/mTOR signaling pathway.

Breast cancer is one of the most common cancers. Oridonin, a traditional Chinese medicine, is believed to inhibit tumor growth, but its particular effects on breast cancer remain unknown. In this study, we examined oridonin's effects on 4T1, MCF-7, and MDAMB-231 cellular activity using CCK8. Scratch assays were used to detect oridonin's effects on cellular migration. Oridonin's effects on the breast cancer cell cycle were studied using flow cytometry, and expression of cell cycle related proteins p53, CDK2, and p21 was detected using Western blot assays. Metabolomics assays were used to detect changes in small molecule metabolites and metabolic pathways in breast cancer cells after treatment with oridonin. Oridonin's effects on breast cancer growth were also studied using xenograft mice. Metabolomics assays were used to detect changes in metabolites and metabolic pathways in xenograft mouse plasma in a control group, model group, and drug administration group. Experimental results showed that oridonin could significantly inhibit breast cancer growth both in vivo and in vitro. Scratch experiments showed that oridonin could inhibit breast cancer cell migration. Oridonin was also able to arrest cells in S phase by affecting several cell cycle-related proteins, including p53, CDK2, and p21. Metabolomic analysis of 4T1 cells identified a total of 33 differential metabolites, including multiple amino acids (such as l-Glutamic acid, l-Asparagine, l-Histidine, l-Valine, and l-Isoleucine). KEGG pathway enrichment analysis showed significant changes in aminoacyl-tRNA biosynthesis, and in multiple amino acid metabolic pathways. Plasma metabolomic analyses of xenograft mice revealed 28 differentially-expressed metabolites between the different animal model groups, including multiple amino acids. KEGG pathway analysis showed significant alterations in multiple amino acid metabolic pathways in oridonin-treated mice. Additionally, changes in the expression of PI3K, AKT and mTOR proteins, as well as in branched amino acids, suggest that oridonin affects the PI3K/AKT/mTOR signaling pathway by inhibiting the biosynthesis of valine, leucine and isoleucine. Taken together, our results suggest that oridonin has strong anti-tumor activity in vitro and in vivo, and has potential as an adjuvant to breast cancer treatment regimens.

Research on the Regulatory Mechanism of Ginseng on the Tumor Microenvironment of Colorectal Cancer based on Network Pharmacology and Bioinformatics Validation.

BACKGROUND: A network pharmacology study on the biological action of ginseng in the treatment of colorectal cancer (CRC) by regulating the tumor microenvironment (TME). OBJECTIVE: To investigate the potential mechanism of action of ginseng in the treatment of CRC by regulating TME. METHOD: This research employed network pharmacology, molecular docking techniques, and bioinformatics validation. Firstly, the active ingredients and the corresponding targets of ginseng were retrieved using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), the Traditional Chinese Medicine Integrated Database (TCMID), and the Traditional Chinese Medicine Database@Taiwan (TCM Database@Taiwan). Secondly, the targets related to CRC were retrieved using Genecards, Therapeutic Target Database (TTD), and Online Mendelian Inheritance in Man (OMIM). Tertiary, the targets related to TME were derived from screening the GeneCards and National Center for Biotechnology Information (NCBI)-Gene. Then the common targets of ginseng, CRC, and TME were obtained by Venn diagram. Afterward, the Protein-protein interaction (PPI) network was constructed in the STRING 11.5 database, intersecting targets identified by PPI analysis were introduced into Cytoscape 3.8.2 software cytoHubba plugin, and the final determination of core targets was based on degree value. The OmicShare Tools platform was used to analyze the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the core targets. Autodock and PyMOL were used for molecular docking verification and visual data analysis of docking results. Finally, we verified the core targets by Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) databases in bioinformatics. RESULTS: A total of 22 active ingredients and 202 targets were identified to be closely related to the TME of CRC. PPI network mapping identified SRC, STAT3, PIK3R1, HSP90AA1, and AKT1 as possible core targets. Go enrichment analysis showed that it was mainly involved in T cell co-stimulation, lymphocyte co-stimulation, growth hormone response, protein input, and other biological processes; KEGG pathway analysis found 123 related signal pathways, including EGFR tyrosine kinase inhibitor resistance, chemokine signaling pathway, VEGF signaling pathway, ErbB signaling pathway, PD-L1 expression and PD-1 checkpoint pathway in cancer, etc. The molecular docking results showed that the main chemical components of ginseng have a stable binding activity to the core targets. The results of the GEPIA database showed that the mRNA levels of PIK3R1 were significantly lowly expressed and HSP90AA1 was significantly highly expressed in CRC tissues. Analysis of the relationship between core target mRNA levels and the pathological stage of CRC showed that the levels of SRC changed significantly with the pathological stage. The HPA database results showed that the expression levels of SRC were increased in CRC tissues, while the expression of STAT3, PIK3R1, HSP90AA1, and AKT1 were decreased in CRC tissues. CONCLUSION: Ginseng may act on SRC, STAT3, PIK3R1, HSP90AA1, and AKT1 to regulate T cell costimulation, lymphocyte costimulation, growth hormone response, protein input as a molecular mechanism regulating TME for CRC. It reflects the multi-target and multi-pathway role of ginseng in modulating TME for CRC, which provides new ideas to further reveal its pharmacological basis, mechanism of action and new drug design and development.

Mechanism and Performance Analysis of Nanoparticle-Polymer Fluid for Enhanced Oil Recovery: A Review.

With the increasing energy demand, oil is still an important fuel source worldwide. The chemical flooding process is used in petroleum engineering to increase the recovery of residual oil. As a promising enhanced oil-recovery technology, polymer flooding still faces some challenges in achieving this goal. The stability of a polymer solution is easily affected by the harsh reservoir conditions of high temperature and high salt, and the influence of the external environment such as high salinity, high valence cations, pH value, temperature and its own structure is highlighted. This article also involves the introduction of commonly used nanoparticles, whose unique properties are used to improve the performance of polymers under harsh conditions. The mechanism of nanoparticle improvement on polymer properties is discussed, that is, how the interaction between them improves the viscosity, shear stability, heat-resistance and salt-tolerant performance of the polymer. Nanoparticle-polymer fluids exhibit properties that they cannot exhibit by themselves. The positive effects of nanoparticle-polymer fluids on reducing interfacial tension and improving the wettability of reservoir rock in tertiary oil recovery are introduced, and the stability of nanoparticle-polymer fluid is described. While analyzing and evaluating the research on nanoparticle-polymer fluid, indicating the obstacles and challenges that still exist at this stage, future research work on nanoparticle-polymer fluid is proposed.

Four new eudesmane-type and one new eremophilane-type sesquiterpenes from the whole plant of Carpesium abrotanoides L.

The extract of the whole plant of Carpesium abrotanoides L. yielded five new sesquiterpenes including four eudesmanes (1-4) and one eremophilane (5). The new compounds were characterized by spectroscopic analysis especially 1D and 2D NMR spectroscopy and HRESIMS data. Structurally, both compounds 1 and 2 were sesquiterpene epoxides and 2 owned an epoxy group at C-4/C-15 position to form a spiro skeleton. Compounds 4 and 5 were two sesquiterpenes without lactones and 5 possessed a carboxy group in the molecule. Additionally, all the isolated compounds were preliminarily evaluated for the inhibitory activity against SARS-CoV-2 main protease. As a result, compound 2 showed moderate activity with an IC50 value of 18.79 µM, while other compounds were devoid of noticeable activity (IC50 > 50 µM).

Clinical efficacy and complications of transurethral resection of the prostate versus plasmakinetic enucleation of the prostate.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease in elderly males, and many kinds of minimally invasive procedures can be used for the treatment of BPH. However, various procedures have caused some controversies regarding clinical outcomes, so more studies are needed to validate these controversial topics. AIMS: This study aimed to explore differences of clinical efficacy, surgical features, and complications between transurethral resection of the prostate (TURP) and plasmakinetic enucleation of the prostate (PKEP) for BPH. METHODS: A total of eligible 850 cases of BPH underwent TURP (the TURP group, 320 cases) or PKEP (the PKEP group, 530 cases) in the urology department of our hospital from March 2015 to 2018 were involved in this study. Then, the baseline data, surgical characteristics, IPSS, QoL, PVR, Qmax, IIEF-5, and documented complications were compared between the two groups. RESULTS: The operative time, intraoperative irrigation volume, postoperative hemoglobin, decrease in hemoglobin, postoperative irrigation time and volume, catheterization time, and hospital stay of the PKEP group were significantly less than those of the TURP group (all P < 0.05). At 3 months, 1, 2, and 3 years after operation, no significant differences were observed in IPSS, QoL, PVR, but the results of Qmax and IIEF-5 in the PKEP group were significantly higher than those parameters in the TURP group (all P < 0.05). The incidences of massive blood loss, postoperative secondary bleeding, blood transfusion, capsular perforation, urinary tract irritation, bladder spasm, clot retention, urinary tract infection, transient incontinence, erectile dysfunction, and the incidences of II, III grade of Clavien-Dindo classification in the PKEP group were significantly lower than those of the TURP group (all P < 0.05). CONCLUSION: The clinical efficacy of PKEP is compared favorably with TURP during midterm follow-up. Given the merits such as less blood loss and hospital stay, lower complications, PKEP should be given a priority for BPH.

Euryachincoside, a Novel Phenolic Glycoside with Anti-Hepatic Fibrosis Activity from Eurya chinensis.

Eurya chinensis has been recorded as a folk medicine traditionally used for treatment of a variety of symptoms. However, the phytochemical and pharmacological investigations of this plant are still scarce. A novel phenolic glycoside named Euryachincoside (ECS) was isolated by chromatographic separation from E. chinensis, and its chemical structure was identified by analysis of HRMS and NMR data. Its anti-hepatic fibrosis effects were evaluated in both HSC-T6 (rat hepatic stellate cells) and carbon tetrachloride (CCl4)-induced mice with Silybin (SLB) as the positive control. In an in vitro study, ECS showed little cytotoxicity and inhibited transforming growth factor-beta (TGF-ß)-induced Collagen I (Col1) along with alpha-smooth muscle actin (α-SMA) expressions in HSC-T6. An in vivo study suggested ECS significantly ameliorated hepatic injury, secretions of inflammatory cytokines, and collagen depositions. Moreover, ECS markedly mediated Smad2/3, nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways both in vitro and vivo. These present findings confirmed that ECS is a novel phenolic glycoside from E. chinensis with promising curative effects on hepatic fibrosis, and its mechanisms may include decreasing extracellular matrix accumulation, reducing inflammation and attenuating free radicals via Smad2/3, NF-κB and Nrf2 signaling pathways, which may shed light on the exploration of more effective phenolic glycoside-based anti-fibrotic agents.

Two new withanolides from the whole plants of Physalis peruviana.

Two new withaphysalin-type withanolides (18-O-ethylwithaphysalin R and 5-O-ethylphysaminimin C, 1 and 2), along with twelve known withanolides (3-14), were purified and identified from Physalis peruviana L. The chemical structures of these new isolates were elucidated through analyzing spectroscopic and HRESIMS data. All the obtained metabolites were appraised for their potential antiproliferative activity against the human breast cancer cell line MCF-7. Compound 7 was discovered to exhibit potent activity with an IC50 value of 3.51 µM and compounds 2, 6 and 14 showed weak cytotoxic effect.

Preparation and Characterization of Polysaccharide-Based Hydrogels for Cutaneous Wound Healing.

Natural hydrogels are growing in interest as a priority for wound healing. Plant polysaccharides have a variety of biological pharmacological activities, and chitosan hydrogels have proven strong antimicrobial effects, but hydrogels prepared with polysaccharides alone have certain deficiencies. Polysaccharides from flowers of Lonicera japonica Thunb. (LP) and the aerial parts of Mentha canadensis L. (MP) were extracted and oxidized by sodium periodate (NaIO4) and then cross-linked with oxidized-carboxymethylated chitosan (O-CCS) to develop oxidized plant- polysaccharides-chitosan hydrogels (OPHs). SEM observation showed that OPHs had porous interior structures with interconnecting pores. The OPHs showed good swelling, water-retention ability, blood coagulation, cytocompatibility properties, and low cytotoxicity (classed as grade 1 according to United States Pharmacopoeia), which met the requirements for wound dressings. Then the cutaneous wound-healing effect was evaluated in BALB/C mice model, after 7 days treatment, the wound-closure rate of OPHs groups were all greater than 50%, and after 14 days, all were greater than 90%, while the value of the control group was only 72.6%. Of them, OPH-2 and OPH-3 were more favorable to the wound-healing process, as the promotion was more significant. The plant polysaccharides and CS-based hydrogel should be a candidate for cutaneous wound dressings.

Arsenic retention in erythrocytes and excessive erythrophagocytosis is related to low selenium status by impaired redox homeostasis.

Arsenic (As) contamination in drinking water is a global public health problem. Epidemiological studies have shown that selenium (Se) deficiency is associated with an increasing risk of arsenism. However, the association between Se status and As retention in erythrocytes and mechanisms underlying this association have not been fully investigated. In the present study, a total of 165 eligible subjects were recruited and As was found to accumulate in blood mainly by retention in erythrocytes. Retention of As in erythrocytes was negatively correlated with Se status, antioxidant parameters related to Se and As methylation capacity, but positively correlated with the protein-binding capacity of As. Additionally, erythrocytes isolated from subjects with low Se status exhibited cellular damage along with lower protein levels of CD47, which could be aggravated by hydrogen peroxide treatment. Consistent with the human study, the erythrocytes from mice with sub-chronic As exposure exhibited similar cellular damage and shown to be phagocytosed by splenic macrophages, and these effects were mitigated by dietary Se supplementation. Furthermore, hydrogen peroxide treatment induced excessive phagocytosis of erythrocytes with As exposure by splenic macrophages, while co-treating erythrocytes with the reducing agent, N-Acetyl-l-cysteine, mitigated this excessive erythrophagocytosis. Hyperactivation of the NFκB pathway was also detected in splenic macrophages after excessive erythrophagocytosis. In conclusion, this study found that low Se status involving impaired redox homeostasis increased As retention in erythrocytes, which were subsequently phagocytosed by splenic macrophages and led to an increased inflammatory status of splenic macrophages. These findings provide insight into physiological features of arsenism related to Se status and redox homeostasis.

Photo-Enhanced Chemotherapy Performance in Bladder Cancer Treatment via Albumin Coated AIE Aggregates.

The implementation of cisplatin-based neoadjuvant chemotherapy (NAC) plays a key role in conjunction with surgical resection in preventing bladder cancer progression and recurrence. However, the significant dose-dependent toxic side effects of NAC are still a major challenge. To solve this problem, we developed a photoenhanced cancer chemotherapy (PECC) strategy based on AIEgen ((E)-3-(2-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-1,1-dimethyl-1H-3λ4-benzo[e]indol-3-yl)propane-1-sulfonate), which is abbreviated as BITT. Multifunctional BITT@BSA-DSP nanoparticles (NPs) were employed with an albumin-based nanocarrier decorated with the cisplatin(IV) prodrug and loaded to produce strong near-infrared fluorescence imaging (NIR FLI), and they exhibited good photoenhancement performance via photodynamic therapy (PDT) and photothermal therapy (PTT). In vitro results demonstrated that BITT@BSA-DSP NPs could be efficiently taken up by bladder cancer cells and reduced to release Pt (II) under reductase, ensuring the chemotherapy effect. Furthermore, both in vitro and in vivo evaluation verified that the integration of NIR FL imaging-guided PECC efficiently promoted the sensitivity of bladder cancer to cisplatin chemotherapy with negligible side effects. This work provides a promising strategy to enhance the sensitivity of multiple cancers to chemotherapy drugs and even achieve effective treatments for drug-resistant cancers.

Solar-assisted high-efficient cleanup of viscous crude oil spill using an ink-modified plant fiber sponge.

Rapid and efficient clean-up of viscous crude oil spills is still a global challenge due to its high viscous and poor flowability at room temperature. The hydrophobic/oleophilic absorbents with three-dimensional porous structure have been considered as a promising candidate to handle oil spills. However, they still have limited application in recovering the high viscous oil. Inspired by the viscosity of crude oil depended on the temperature, a solar-heated ink modified plant fiber sponge (PFS@GC) is fabricated via a simple and environmentally friendly physical foaming strategy combined with in-situ ink coating treatment. After wrapping by the polydimethylsiloxane (PDMS), the modified PFS@GC (PFS@GC@PDMS) exhibits excellent compressibility, high hydrophobic (141° in water contact angle), solar absorption (> 96.0%), and oil absorptive capacity (12.0-27.8 g/g). Benefiting from the favorable mechanical property and photothermal conversion capacity, PFS@GC@PDMS is demonstrated as a high-performance absorbent for crude oil clean-up and recovery. In addition, PFS@GC@PDMS can also be applied in a continuous absorption system for uninterrupted recovering of oil spills on the water surface. The proposed solar-heated absorbent design provides a new opportunity for exploring biomass in addressing large-scale oil spill disasters.

Rosavin suppresses osteoclastogenesis in vivo and in vitro by blocking the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways.

BACKGROUND: Bone homeostasis is mediated by osteoblast-related bone formation and osteoclast-related resorption. The imbalance of bone homeostasis due to excessive osteoclastogenesis or reduced osteogenesis can result in various disorders, such as postmenopausal osteoporosis (PMOP). The receptor activator of nuclear factor-κB ligand (RANKL)-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) pathways are essential in osteoclastogenesis. In this study, we aimed to investigate the effects of rosavin, an alkylbenzene diglycoside compound from the traditional Chinese medicine Rhodiola Rosea L, on RANKL-induced osteoclastogenesis in vitro and in vivo. METHODS: The effects of rosavin on osteoclastogenesis were assessed by TRAP staining of bone marrow monocyte cells (BMMCs) and RAW 264.7 cells. The effects of rosavin on osteogenesis were determined using alkaline phosphatase (ALP) and alizarin red staining, as well as real-time quantitative reverse transcription polymerase chain reaction. Actin ring formation and bone formation experiments were performed to evaluate osteoclast function. Western blotting was carried out to determine the expression of osteoclastogenesis-related genes, and the activation of the NF-κB and MAPK pathways was evaluated by performing western blotting and immunofluorescence staining. Ovariectomized mice were used to explore the effect of rosavin on bone loss. RESULTS: Rosavin could inhibit osteoclastogenesis, suppress the function of osteoclasts, and decrease the expression of osteoclast differentiation-related genes, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, matrix metalloproteinase-9 (MMP-9), calcitonin receptor (CTR), TNF receptor-associated factor 6 (TRAF-6), receptor activator of nuclear factor-κB (RANK), and colony-stimulating factor-1 receptor (c-fms). Rosavin inhibited RANKL-induced phosphorylation of p65 and inhibitory subunit of NF-κB alpha (IκBα), and suppressed p65 nuclear translocation. Rosavin was also found to inhibit the phosphorylation of extracellular-signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). Furthermore, rosavin promoted osteogenesis in bone marrow mesenchymal stem cells (BMSCs). In vivo experiments showed that treatment with rosavin could alleviate ovariectomy-induced osteoporosis in mice. CONCLUSIONS: Our results indicated that rosavin suppressed RANKL-induced osteoclastogenesis in vivo and in vitro by blocking the NF-κB and MAPK pathways. Rosavin treatment is a potential therapy for the clinical treatment of osteoclastogenesis-related disorders.

Withdrawing mycophenolate mofetil in treating a young kidney transplant recipient with COVID-19: A case report.

RATIONALE: Coronavirus disease 2019 (COVID-19) is a novel infectious disease and became a global issue. Treatment of COVID-19 especially in solid organ transplant recipients is empirical and controversial, especially the adjustment of the immunosuppressants. PATIENT CONCERNS: A 29-year-old kidney transplant recipient with the symptoms of COVID-19 pneumonia. DIAGNOSES: COVID-19 pneumonia after kidney transplantation. INTERVENTIONS: He was treated with modified immunosuppressants (unchanged dose of tacrolimus and oral corticosteroids while discontinuing mycophenolate mofetil (MMF)), antibiotics, interferon α-2b inhalation and traditional Chinese medicine. OUTCOMES: He recovered from COVID-19 pneumonia after 29 days of hospitalization. And the renal function (measured as blood urea nitrogen, serum creatinine, and urine protein) returned to normal. LESSONS: In certain group of COVID-19 (e.g., mild to moderate cases, young patients without comorbidities), a reduction instead of an overall withdrawal of immunosuppressant in kidney transplant recipients is feasible.

Highly efficient electrocatalytic hydrogen evolution promoted by O-Mo-C interfaces of ultrafine ß-Mo2C nanostructures.

Optimizing interfacial contacts and thus electron transfer phenomena in heterogeneous electrocatalysts is an effective approach for enhancing electrocatalytic performance. Herein, we successfully synthesized ultrafine ß-Mo2C nanoparticles confined within hollow capsules of nitrogen-doped porous carbon (ß-Mo2C@NPCC) and found that the surface layer of molybdenum atoms was further oxidized to a single Mo-O surface layer, thus producing intimate O-Mo-C interfaces. An arsenal of complementary technologies, including XPS, atomic-resolution HAADF-STEM, and XAS analysis clearly reveals the existence of O-Mo-C interfaces for these surface-engineered ultrafine nanostructures. The ß-Mo2C@NPCC electrocatalyst exhibited excellent electrocatalytic activity for the hydrogen evolution reaction (HER) in water. Theoretical studies indicate that the highly accessible ultrathin O-Mo-C interfaces serving as the active sites are crucial to the HER performance and underpinned the outstanding electrocatalytic performance of ß-Mo2C@NPCC. This proof-of-concept study opens a new avenue for the fabrication of highly efficient catalysts for HER and other applications, whilst further demonstrating the importance of exposed interfaces and interfacial contacts in efficient electrocatalysis.

Impact of traditional Chinese medicine treatment on chronic unpredictable mild stress-induced depression-like behaviors: intestinal microbiota and gut microbiome function.

Gut microbiota dysbiosis is a recognized contributing factor to many noncommunicable diseases, but more evidence is still needed to illustrate its causative impact on mental and brain health disorders and mechanism(s) for targeted mitigation. Traditional Chinese Medicine (TCM) has been used in the management of neuropsychiatric diseases for many years in China. In this study, a randomized, controlled trial was conducted to examine the impact of stress on gut microbiota dysbiosis and depression, and TCM in alleviating the damage using Chronic Unpredictable Mild Stress (CUMS) rats, a well-established rodent model for depression. The behaviors of rats and the profiles of the fecal microbiota were assessed by an array of behavioral tests and 16S rRNA gene sequencing, and the intestinal microbial function was assessed by shotgun sequencing-based metagenomic analysis of microbial DNA from fecal samples. Data on brain targeted metabolites by liquid chromatography-mass spectrometry (LC-MS) were also discussed. Depressive and anxiety-like behaviors and changes in the fecal microbiota profile were observed in CUMS rats, which were then significantly reversed in CUMS rats that received TCM. Specifically, TCM treatment reduced the levels of Firmicutes, and Ruminococcus, and increased the abundance of Bacteroidetes and Roseburia, reportedly being associated with relieving psychiatric disorders. Furthermore, the levels of brain metabolites perturbed by CUMS were reversed by TCM treatment, and Spearman's correlation analysis illustrated strong correlation between brain metabolites and perturbed fecal microbiota genera. Finally, the fecal microbiome of CUMS rats was characterized by alterations in amino acid metabolism and evaluation of bile acid biosynthesis, and TCM-treated rats showed elevation of cysteine and methionine metabolism. Overall, these results indicated that administration of the TCM may mitigate CUMS-induced depression-behaviors, and it is correlated with reversing CUMS-induced intestinal microbiota dysbiosis; evidence also supported related changes in brain metabolites. These findings set up the foundation to further reveal the exact causal relationship among the TCM formula, host responses, gut microbiota dysbiosis and the levels of brain metabolites, and enabled scientific interpretation of the therapeutic function of the TCM.

Protective effect of curcumin against irinotecan­induced intestinal mucosal injury via attenuation of NF­κB activation, oxidative stress and endoplasmic reticulum stress.

Irinotecan (CPT­11) is a DNA topoisomerase I inhibitor which is widely used in clinical chemotherapy, particularly for colorectal cancer treatment. However, late­onset diarrhea is one of the severe side­effects of this drug and this restricts its clinical application. The present study aimed to investigate the protective effects of curcumin treatment on CPT­11­induced intestinal mucosal injury both in vitro and in vivo and to elucidate the related mechanisms involved in these effects. For this purpose, mice were intraperitoneally injected with CPT­11 (75 mg/kg) for 4 days to establish a model of late­onset diarrhea. Curcumin (100 mg/kg) was intragastrically administered 8 days before the injection of CPT­11. Injury to small intestinal tissues was examined by H&E staining. The protein expression of prolyl 4­hydroxylase subunit beta (P4HB) and peroxiredoxin 4 (PRDX4) was detected by immunohistochemistry, as well as western blot analysis. IEC­6 cell viability was detected by MTT assay. Flow cytometry was performed to examine the cell apoptotic rate, mitochondrial membrane potential and reactive oxygen species (ROS) generation. Immunofluorescence was used to observe the localization of nuclear factor (NF)­κB. The levels of cleaved caspase­3, glucose­regulated protein, 78 kDa (GRP78), P4HB, PRDX4 and CHOP were detected by western blot analysis. The results revealed that in vivo, curcumin effectively attenuated the symptoms of diarrhea and abnormal intestinal mucosa structure induced by CPT­11 in nude mice. Treatment with curcumin also increased the expression of P4HB and PRDX4 in the tissue of the small intestine. In vitro, curcumin, exhibited little cytotoxicity when used at concentrations <2.5 µg/ml for 24 h in IEC­6 cells. At this concentration, curcumin also improved cell morphology, inhibited apoptosis, maintained mitochondrial membrane potential and reduced the elevated levels of ROS induced by CPT­11 (20 µg/ml). Furthermore, curcumin abolished NF­κB signal transduction and protected the cells from CPT­11­induced apoptosis by upregulating the expression of molecular chaperones, such as GRP78, P4HB and PRDX4, and suppressing the levels of the apoptosis­related proteins, CHOP and cleaved caspase­3. On the whole, our data indicate that curcumin exerted protective effects against CPT­11­induced intestinal mucosa injury. The protective effects of curcumin are mediated by inhibiting the activation of NF­κB, and suppressing oxidative stress and endoplasmic reticulum stress.

Influence of Chronic Toxicity, Lipid Metabolism, Learning and Memory Ability, and Related Enzyme in Sprague-Dawley Rats by Long-Term Chromium Malate Supplementation.

In our previous study, chromium malate is beneficial for type 2 diabetic rats in control glycometabolism and lipid metabolism. The present study was designed to observe the chronic toxicity, lipid metabolism, learning and memory ability, and related enzymes of chromium malate in rats during the year. The results showed that pathological, toxic, feces, and urine of chromium malate (at daily doses of 10.0, 15.0, and 20.0 µg Cr/kg bm) did not change measurably. Chromium malate (at daily doses of 15.0 and 20.0 µg Cr/kg bm) could significantly reduce the levels of total cholesterol (TC), LDL, and triglyceride (TG), and increase the level of HDL in male rats compared to control group and chromium picolinate group. Significant escalating trends of the escape latency and swimming speed (Morris water maze test), and the original platform quadrant stops, residence time, and swimming speed (Space exploration test) in male rats of chromium malate groups were obtained. The SOD, GSH-Px, and TChE activities of chromium malate (at daily doses of 15.0 and 20.0 µg Cr/kg bm) were enhanced significantly in male rats compared with those of the normal control group and chromium picolinate group. Glycometabolism and related enzymes had no significant changes compared to normal control group and chromium picolinate group. These results indicated that long-term chromium malate supplementation did not cause measurable toxicity at daily doses of 10.0, 15.0, and 20.0 µg Cr/kg bm and could improve dyslipidemia and learning and memory deficits.