Andrographolide promotes lymphangiogenesis and lymphatic vessel remodeling to alleviate secondary lymphedema.

Lymphedema, a prevalent, multifaceted, and chronic ailment, is mainly managed through physical manipulation and suffers from a lack of specific pharmacological treatments. Secondary lymphedema is mainly caused by impaired lymphatic drainage. Therapeutic lymphangiogenesis is a promising strategy in the treatment of lymphedema. Andrographolide, a natural product from Andrographis paniculata, is unknown whether andrographolide promotes lymphangiogenesis to improve secondary lymphedema. By using the murine tail lymphedema model, we demonstrated that andrographolide can reduce the thickness of subcutaneous tissue in the mice's tail and enhance lymphatic drainage. Moreover, immunofluorescence staining showed that the number of capillary lymphatic vessels in the ANDRO25 group was significantly more than that in the ANDRO50 and Model groups. Near-infrared lymphography images showed that highlighted sciatic lymph nodes could be seen in the ANDRO25 and ANDRO50 groups. In vitro, andrographolide could promote the proliferation and migration of LEC. In conclusion, andrographolide enhanced the recovery of lymphatic vessels, and promoted lymphatic drainage in the murine tail lymphedema model by promoting the proliferation of lymphatic endothelial cells, thereby reducing the symptoms of lymphedema. This suggested andrographolide may be used as a potential therapeutic drug or medical food ingredient to help patients with secondary lymphedema.

Hepatorenal pathologies in TNF-transgenic mouse model of rheumatoid arthritis are alleviated by anti-TNF treatment.

OBJECTIVE: To examine and quantify liver and kidney lesions and their response to anti-tumor necrosis factor (TNF) therapy in a TNF-Tg mouse model of rheumatoid arthritis (RA). METHODS: Female TNF-Tg (Tg3647) mice were used as the animal model for chronic RA. Ultrasound, immunofluorescence, histological staining, serology tests, and real-time RT-PCR were used to examine the pathological changes in the liver and kidney. RESULTS: TNF-Tg mice showed a significant decrease in the body weight and a dramatic increase in the volumes of the gallbladder, knee cavity, and popliteal lymph nodes. The liver and kidneys of TNF-Tg mice showed increased chronic inflammation and accumulation of immune cells and fibrosis, compared to wild-type (WT) mice. Moreover, upregulation of inflammatory factors and impaired normal function were observed in the liver and kidneys of TNF-Tg mice. Inflammatory infiltration and fibrosis of the liver and kidneys of female TNF-Tg mice were improved after anti-TNF treatment, and better treatment effects were achieved at 4.5-month-old mice when they were received 8 weeks of intervention. CONCLUSIONS: We found that TNF drives the development of liver and kidney pathology in female TNF-Tg mice and that there are limitations to the loss of utility of anti-TNF for the prolonged treatment of RA-associated hepatic and renal injury. This study provides a reliable and clinically relevant animal model for further studies exploring the molecular mechanisms and drug discovery for hepatorenal pathologies in RA.

Network pharmacology, a promising approach to reveal the pharmacology mechanism of Chinese medicine formula.

ETHNOPHARMACOLOGICAL RELEVANCE: Network pharmacology is a new discipline based on systems biology theory, biological system network analysis, and multi-target drug molecule design specific signal node selection. The mechanism of action of TCM formula has the characteristics of multiple targets and levels. The mechanism is similar to the integrity, systematization and comprehensiveness of network pharmacology, so network pharmacology is suitable for the study of the pharmacological mechanism of Chinese medicine compounds. AIM OF THE STUDY: The paper summarizes the present application status and existing problems of network pharmacology in the field of Chinese medicine formula, and formulates the research ideas, up-to-date key technology and application method and strategy of network pharmacology. Its purpose is to provide guidance and reference for using network pharmacology to reveal the modern scientific connotation of Chinese medicine. MATERIALS AND METHODS: Literatures in this review were searched in PubMed, China National Knowledge Infrastructure (CNKI), Web of Science, ScienceDirect and Google Scholar using the keywords "traditional Chinese medicine", "Chinese herb medicine" and "network pharmacology". The literature cited in this review dates from 2002 to 2022. RESULTS: Using network pharmacology methods to predict the basis and mechanism of pharmacodynamic substances of traditional Chinese medicines has become a trend. CONCLUSION: Network pharmacology is a promising approach to reveal the pharmacology mechanism of Chinese medicine formula.

Theoretical study on ferroelectric nitrides with super-wurtzite structures for solar energy conversion applications.

Polarized structured nitride semiconductors are attractive due to their unique and environment-friendly electronic properties. The stability, ferroelectricity and photocatalytic and photovoltaic properties of super-wurtzite Mg2XN3 (X = Bi, Mo, Nb, Sb, Ta, Tc and W) were determined based on first principles calculations in this study. The calculated results indicate that Mg2XN3 (X = Sb, Ta, Bi and Nb) are stable polar nitrides by phonon frequencies, elastic coefficients and ferroelectric analysis. Mg2XN3 (X = Sb, Ta and Nb) with large ferroelectric polarization strength could absorb ultraviolet light to promote photocatalytic water splitting for hydrogen production. Mg2BiN3 is a new excellent photovoltaic candidate due to its ideal energy band, high electron mobility, high absorption coefficient and large ferroelectric polarization strength.

The lymphatic drainage system of the CNS plays a role in lymphatic drainage, immunity, and neuroinflammation in stroke.

The lymphatic drainage system of the central nervous system (CNS) plays an important role in maintaining interstitial fluid balance and regulating immune responses and immune surveillance. The impaired lymphatic drainage system of the CNS might be involved in the onset and progression of various neurodegenerative diseases, neuroinflammation, and cerebrovascular diseases. A significant immune response and brain edema are observed after stroke, resulting from disrupted homeostasis in the brain. Thus, understanding the lymphatic drainage system of the CNS in stroke may lead to the development of new approaches for therapeutic interventions in the future. Here, we review recent evidence implicating the lymphatic drainage system of the CNS in stroke.

Metformin inhibits cervical cancer cell proliferation by modulating PI3K/Akt-induced major histocompatibility complex class I-related chain A gene expression.

BACKGROUND: Recent studies have shown that the classic hypoglycemic drug metformin inhibits tumor growth; however, the underlying mechanism remains unclear. We previously showed that metformin disrupts the sponge effect of long non-coding RNA MALAT1/miR-142-3p to inhibit cervical cancer cell proliferation. In this study, we interrogated the ability of metformin to modulate the anti-tumor immune response in cervical cancer. METHODS: The cell counting kit-8 assay was used to detect the viability of cervical cancer cells. Flow cytometry assays were performed to measure cell apoptosis and cell cycle. Lactate dehydrogenase (LDH) cytotoxicity assay was used to detect NK Cell Cytotoxicity. Relative protein levels were determined by immunoblotting and relative gene levels were determined by quantitative real-time PCR. Tumor Xenograft Modeling was used to evaluate the effect of metformin in vivo. RESULTS: Metformin inhibited cervical cancer cell proliferation, cervical cancer xenograft growth, expression of PCNA, p-PI3K and p-Akt. Moreover metformin induced cervical cancer cell apoptosis and caused cancer cell cycle arrest. In addition, metformin upregulated the expression of DDR-1 and p53 in human cervical cancer cells. Furthermore, metformin also regulated the mRNA and protein expression of MICA and HSP70 on the surface of human cervical cancer cells via the PI3K/Akt pathway, enhancing NK cell cytotoxicity. CONCLUSIONS: In conclusion, our results suggest that metformin may be used as immunopotentiator to inhibit cervical cancer progression and may be considered a viable candidate for combination therapy with immunotherapy.

Meningeal lymphatics clear erythrocytes that arise from subarachnoid hemorrhage.

Extravasated erythrocytes in cerebrospinal fluid (CSF) critically contribute to the pathogenesis of subarachnoid hemorrhage (SAH). Meningeal lymphatics have been reported to drain macromolecules and immune cells from CSF into cervical lymph nodes (CLNs). However, whether meningeal lymphatics are involved in clearing extravasated erythrocytes in CSF after SAH remains unclear. Here we show that a markedly higher number of erythrocytes are accumulated in the lymphatics of CLNs and meningeal lymphatics after SAH. When the meningeal lymphatics are depleted in a mouse model of SAH, the degree of erythrocyte aggregation in CLNs is significantly lower, while the associated neuroinflammation and the neurologic deficits are dramatically exacerbated. In addition, during SAH lymph flow is increased but without significant lymphangiogenesis and lymphangiectasia. Taken together, this work demonstrates that the meningeal lymphatics drain extravasated erythrocytes from CSF into CLNs after SAH, while suggesting that modulating this draining may offer therapeutic approaches to alleviate SAH severity.

Bioremediation of tetracycline antibiotics-contaminated soil by bioaugmentation.

Bioaugmentation using specific microbial strains or consortia was deemed to be a useful bioremediation technology for increasing bioremediation efficiency. The present study confirmed the effectiveness and feasibility of bioaugmentation capability of the bacterium BC immobilized on sugarcane bagasse (SCB) for degradation of tetracycline antibiotics (TCAs) in soil. It was found that an inoculation dose of 15% (v/w), 28-43 °C, slightly acidic pH (4.5-6.5), and the addition of oxytetracycline (OTC, from 80 mg kg-1 to 160 mg kg-1) favored the bioaugmentation capability of the bacterium BC, indicating its strong tolerance to high temperature, pH, and high substrate concentrations. Moreover, SCB-immobilized bacterium BC system exhibited strong tolerance to heavy metal ions, such as Pb2+ and Cd2+, and could fit into the simulated soil environment very well. In addition, the bioaugmentation and metabolism of the co-culture with various microbes was a complicated process, and was closely related to various species of bacteria. Finally, in the dual-substrate co-biodegradation system, the presence of TC at low concentrations contributed to substantial biomass growth but simultaneously led to a decline in OTC biodegradation efficiency by the SCB-immobilized bacterium BC. As the total antibiotic concentration was increased, the OTC degradation efficiency decreased gradually, while the TC degradation efficiency still exhibited a slow rise tendency. Moreover, the TC was preferentially consumed and degraded by continuous introduction of OTC into the system during the bioremediation treatment. Therefore, we propose that the SCB-immobilized bacterium BC exhibits great potential in the bioremediation of TCAs-contaminated environments.

Bone mesenchymal stem cell therapy for ovariectomized osteoporotic rats: a systematic review and meta-analysis.

BACKGROUND: Previous studies have found that bone mesenchymal stem cells (BMSCs) were capable of self-replication, multi-differentiation, and regeneration. The aim of this study was to carry out a systematic review and meta-analysis of the efficacy of BMSC therapy for ovariectomized rats. METHODS: The PubMed, Embase, Web of Science, China National Knowledge Infrastructure, VIP, and Chinese Sinomed databases were searched systematically from their initiation date to October 5, 2018. Two researchers independently screened the literatures, which used the bone mineral density (BMD), total bone volume by total tissue volume (BV/TV) (%), and trabecular thickness/spacing (Tb/Sp) as the outcome measures. RESULTS: Five eligible studies were selected. In the BMSC treatment groups, the BMD values and normalized BV/TV values remarkably increased. In addition, in the BMSCs plus other treatment groups, the BMD and Tb/Sp values significantly increased. CONCLUSION: This study showed that BMSCs could accelerate callus maturity, ossification and restore mechanical properties of bones in osteoporotic fractures.

Therapeutic effects of whole-body vibration on fracture healing in ovariectomized rats: a systematic review and meta-analysis.

OBJECTIVE: Whole-body vibration (WBV), providing cyclic mechanical stimulation, has been used to accelerate fracture healing in preclinical studies. This study aimed to summarize and evaluate the effects of WBV on bone healing in ovariectomized rat models and then analyze its potential effects on fractures in human postmenopausal osteoporosis. METHODS: PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, VIP, SinoMed, and WanFang databases were searched from their inception date to September 2017, and an updated search was conducted in January 2018. Studies that evaluated the effects of WBV on bone healing compared with control groups in ovariectomized rats were included. Two authors selected studies, extracted data, and assessed the methodological quality. Meta-analyses were performed when the same outcomes were reported in two or more studies. RESULTS: Nine eligible studies were selected. In treatment groups, callus areas were significantly improved in the first 3 weeks, normalized total bone volume and total tissue volume values increased dramatically at 8 weeks, and the mechanical tests showed a significant difference at the end point of the study. CONCLUSIONS: This study suggested that WBV could accelerate callus formation in the early phase of bone healing, promote callus mineralization and maturity in the later phase, and restore mechanical properties of bones.

Metformin, a first-line drug for type 2 diabetes mellitus, disrupts the MALAT1/miR-142-3p sponge to decrease invasion and migration in cervical cancer cells.

The molecular mechanisms underlying the anti-neoplastic properties of metformin, a first-line drug for type 2 diabetes, remain elusive. To explore the novel anti-neoplastic mechanisms of metformin, the transwell chamber and wound-healing assays were used to evaluate its effects on the migration and invasion of human cervical cancer cells. Real-time PCR and Western blotting were used to measure the gene and protein expression, respectively, of microRNA (miRNA) miR-142-3p, long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript-1 (MALAT1), and high-mobility group AT-hook 2 (HMGA2). The dual-luciferase reporter assay system was used to examine the direct interaction between miR-142-3p and lncRNA MALAT1 and HMGA2. Immunofluorescence was used to detect the protein expression of HMGA2. In addition, tumor xenografts in a nude mouse model were developed to evaluate the anti-tumor efficacy of metformin. We found that metformin could suppress cervical cancer migration and invasion. During the process of tumor metastasis, miR-142-3p was significantly upregulated, whereas lncRNA MATAL1 and HMGA2 were suppressed by metformin. The binding site that allow the direct interaction between miR-142-3p and MALAT1 were located in the 3' untranslated region (3' UTR) of lncRNA MATAL1 and HMGA2 at base pairs (bp) 4452-5255, while that between miR-142-3p and HMGA2 was located at bp 1562-2521 of HMGA2. Metformin markedly inhibited the growth and angiogenesis of SiHa xenografts in nude mice. In conclusion, this study provides evidence that metformin can prevent the MALAT1/miR-142-3p sponge from developing anti-neoplastic properties in human cervical cancer cells and cervical cancer cell xenografts in nude mice. Thus, our findings demonstrate the novel anti-tumor effects of metformin in cervical cancer.

Combining metformin and nelfinavir exhibits synergistic effects against the growth of human cervical cancer cells and xenograft in nude mice.

Human cervical cancer is the fourth most common carcinoma in women worldwide. However, the emergence of drug resistance calls for continuously developing new anticancer drugs and combination chemotherapy regimens. The present study aimed to investigate the anti-cervical cancer effects of metformin, a first-line therapeutic drug for type 2 diabetes mellitus, and nelfinavir, an HIV protease inhibitor, when used alone or in combination. We found that both metformin and nelfinavir, when used alone, were moderately effective in inhibiting proliferation, inducing apoptosis and suppressing migration and invasion of human cervical cell lines HeLa, SiHa and CaSki. When used in combination, these two drugs acted synergistically to inhibit the growth of human cervical cancer cells in vitro and cervical cancer cell xenograft in vivo in nude mice, and suppress cervical cancer cell migration and invasion. The protein expression of phosphoinositide 3-kinase catalytic subunit PI3K(p110α), which can promote tumor growth, was remarkably downregulated, while the tumor suppressor proteins p53 and p21 were substantially upregulated following the combinational treatment in vitro and in vivo. These results suggest that clinical use of metformin and nelfinavir in combination is expected to have synergistic antitumor efficacy and significant potential for the treatment of human cervical cancer.

A flavonoid 8-C-glycoside and a triterpenoid cinnamate from Nervilia fordii.

One new flavonoid glycoside (1) and one new triterpenoid cinnamate (2) were isolated from Nervilia fordii. The structures of 1 and 2 were determined by extensive NMR and HRESIMS to be 7-O-ß-d-glucopyranosylapigenin-8-C-ß-d-glucopyranosyl-(1 â†’ 2)-ß-d-glucopyranoside and 24(S/ß)-dihydrocycloeucalenol-3-(Z)-p-hydroxycinnamate, respectively.

[Chemical constituents contained in roots of Pterospermum heterophyllum].

OBJECTIVE: To study chemical constituents of contained in roots of Pterospermum heterophyllum. METHOD: The chemical constituents of P. heterophyllum were separated and purified by silica gel, sephadex LH-20, ODS column chromatography and preparative HPLC. Their structures were identified by spectroscopic techniques. RESULT: Ten compounds were separated and identified as asperglaucide (1), 2-methoxy4-hydroxyphenol-1-O-beta-D-apiofuranosyl (1-->6)-O-beta-D-glucopyranoside (2), 5, 5'-dimethoxy-9-beta-D-xylopyranosyl-(-) -isolariciresinol(3), (-)-epicatechin (4), eriodictyol (5), taxifolin (6), 3beta-hydroxy-12-en-28-ursolic acid (7), 2beta, 3beta-dihydroxy-12-en-28-oleanolic acid (8), quercetin (9), cholest-4-en-3-one (10). CONCLUSION: Compounds 1-10 were separated from this plant for the first time.

Three new cycloartane glycosides from Nervilia fordii.

From the water-soluble extract of the aerial part of herbal plant Nervilia fordii, three new cycloartane glycosides, named as nervisides A (1), B (2), and C (3), were isolated. Their structures were elucidated through a combination of spectroscopic analysis and hydrolysis. At the same time, the new compounds were tested for their cytotoxicities in vitro against human tumor cell lines (CNE, Hep-2, and HepG2) using MTT method.