Amelioration of histological changes and associated metabolic abnormalities by a combination of Morinda lucida and metformin in diabetic rats

This work investigates the ability of Morinda lucida and co-administration of Morinda lucida/metformin in the control of biochemical and histological changes in alloxan-induced diabetic rats. Alloxan diabetic rats were treated with 200 mg/Kg body weight of Morinda lucida leaves extract, 1 mg/Kg BW of metformin or a combination of the two treatments for 28 days. Results of the studies revealed that Morinda lucida leaves extract significantly improved lipid profile and kidney function in diabetic rats. These positive outcomes were enhanced by combined treated with Morinda lucida leaves extract and metformin. Furthermore, the calculated atherogenic index of treated animals were close to those of normal rats as opposed to diabetic rats. Similarly, histological studies showed that Morinda lucida leaves extract and metformin administered together or singly, ameliorated damages in pancreas and kidneys from alloxan diabetic rats. It can therefore be inferred that combined treatment with Morinda lucida leaves extract and merformin could improve the potency of Morinda lucida leaves used in the management of diabetic complications

Exosomal miRNA-455 from Bone Marrow Stromal Cells (BMSCs) Promotes Macrophage Phagocytosis and Restrains Progression of Gastric Cancer (GC)

Multiple miRNAs are differentially expressed in gastric cancer (GC). Herein, this study aims to investigate miR-455’s role in GC and its mechanism. Exosomes (exo) separated from BMSCs after transfection were co-cultured with either phagocytes, GC cells (NCI-N87 cell), or macrophages combined with NCI-N87cells (mixed group) followed by analysis of the expression of PTEN, N-cadherin, E-cadherin, and PI3K, and AKT by RT-qPCR and Western blot. Increased miR-455 expression was observed in GC cells upon transfection. GC cells in the mixed group relative to NCI-N87 group exhibited a lower cell migration and invasion and impaired proliferative capacity (p < 0.05), accompanied with higher expressions of N-cadherin, E-cadherin, PI3K, and AKT, and decreased level of PTEN (p < 0.05). The combined treatment resulted in a higher phagocytic rate (12.38±0.21%) and phagocytic index (14.29±2.11%) compared to treatment with only phagocytes (p < 0.05). In conclusion, BMSC-derived exosomal miR-455 inhibits the growth of GC cells and promotes the phagocytosis through inactivating PI3K/AKT signaling pathway.

Physiological, Pathological and Pharmacological Interactions of Hydrogen Sulphide and Nitric Oxide in the Myocardium of Rats with Left Ventricular Hypertrophy

Left ventricular hypertrophy (LVH) is characterized by increased myocardium thickness due to increased oxidative stress and downregulation of cystathione γ lyase (CSE) endothelial nitric oxide synthase (eNOS). Upregulation of CSE by hydrogen sulphide (H2S) and ENOS by L-arginine can arrest the progression of LVH individually. The present study explored the combined treatment of H2S and NO in the progression of LVH, and demonstrated that the response is due to H2S, NO or formation of either new molecule in physiological, pathological, and pharmacological in vivo settings of LVH. Exogenous administration H2S+NO in LVH significantly reduced (all p < 0.05) systolic blood pressure (SBP) and mean arterial pressure (MAP), LV index, heart index and oxidative stress when compared to the LVH group. There was downregulation of CSE mRNA and eNOS in the heart, and exogenous administration of H2S+NO groups upregulated eNOS MRNA while CSE MRNA remained downregulated in the hearts of the LVH group. Similar trends were observed with concentrations of H2S and NO in the plasma and tissue. It can be concluded that combined treatment of LVH with H2S and NO significantly ameliorate the progression of LVH by attenuating systemic hemodynamic and physical indices, and by decreasing oxidative stress. Molecular expression data in the myocardium of LVH depicts that combined treatment upregulated eNOS/NO while it downregulated CSE/H2S pathways in in vivo settings, and it is always eNOS/NO pathways which play a major role.

Combination of Anlotinib and Celecoxib for the Treatment of Abdominal Desmoid Tumor: A Case Report and Literature Review

Desmoid tumor is a rare disease, which is histologically characterized by local invasion, monoclonality, and fibroblast proliferation; and clinically characterized by a variable and often unpredictable course. The treatment of desmoid tumor is mainly surgical resection, but the recurrence rate is high. In recent years, a variety of treatment methods, including endocrine therapy, surgery, radiotherapy, chemotherapy, non-steroidal anti-inflammatory drugs, targeted drugs, interferon and more, have been used and achieved certain curative effects. In addition, in view of the inertia characteristics of desmoid tumor, observation is also a first-line scheme recommended by multiple guidelines. In the past, the research progress of targeted therapy for desmoid tumor is relatively slow and the curative effect is limited. Thus, targeted therapy is usually used as a remedial treatment after the failure of other conventional treatment methods. However, in recent years, with the rapid progress in the basic research of targeted therapy, some new targeted drugs are increasingly used for the clinical treatment of desmoid tumor and have achieved good results. Herein, we described a patient with aggressive fibromatosis in the abdominal cavity. Following a combined treatment using anlotinib and celecoxib, the patient achieved a partial response with mild toxicity. Simultaneously, the patient’s pain symptoms completely disappeared. This case indicates that the combination of anlotinib and NSAIDs could be an effective treatment for desmoid tumor.

Intensity-Modulated Radiotherapy with Regional Hyperthermia for High-Risk Localized Prostate Carcinoma

Background: The purpose of this study was to evaluate the efficacy and toxicity of adding regional hyperthermia to intensity-modulated radiotherapy (IMRT) plus neoadjuvant androgen deprivation therapy (ADT) for high-risk localized prostate carcinoma. Methods: Data from 121 consecutive patients with high-risk prostate carcinoma who were treated with IMRT were retrospectively analyzed. The total planned dose of IMRT was 76 Gy in 38 fractions for all patients; hyperthermia was used in 70 of 121 patients. Intra-rectal temperatures at the prostate level were measured to evaluate thermal dose. Results: Median number of heating sessions was five and the median total thermal dose of CEM43T90 was 7.5 min. Median follow-up duration was 64 months. Addition of hyperthermia to IMRT predicted better clinical relapse-free survival. Higher thermal dose with CEM43T90 (>7 min) predicted improved biochemical disease-free survival. The occurrence of acute and delayed toxicity ≥Grade 2 was not significantly different between patients with or without hyperthermia. Conclusions: IMRT plus regional hyperthermia represents a promising approach with acceptable toxicity for high-risk localized prostate carcinoma. Further studies are needed to verify the efficacy of this combined treatment.

CO2, Environmental Emergencies, and Industrial Pollution Assessment in China from the Perspective of the Circular Economy

The rise of energy consumption has also increased emissions of the “three wastes” (wastewater, waste gas, and industrial solid waste), and environmental emergencies caused by pollutants, natural disasters, and production safety accidents have aroused social concerns. As few scholars have combined treatment efficiency of the three wastes with environmental emergencies to explore their relationships, this research thus uses a two-stage undesirable Data Envelopment Analysis (DEA) method to explore the situations of 4 regions and 30 provinces in China from 2013 to 2017 based on such interactive perspectives. The study finds that the overall regional environmental efficiency in China is generally low, and in terms of regional differences, the eastern and northeastern regions are better than the central and western regions. The efficiency values of the three wastes in China have also fluctuated greatly from 0.7 down to 0.2 in recent years. The efficiency of environmental emergencies in China is greatly impacted by the efficiency of environmental governance inputs. Based on the results, the study proposes that the eastern provinces can be an example for promoting balanced regional development and offers policy recommendations such as taking precautions against environmental emergencies.

Treatment Combining Focused Ultrasound with Gastrodin Alleviates Memory Deficit and Neuropathology in an Alzheimer’s Disease-Like Experimental Mouse Model

Alzheimer’s disease (AD) is the most common type of dementia but lacks effective treatment at present. Gastrodin (GAS) is a phenolic glycoside extracted from the traditional Chinese herb—Gastrodia elata—and has been reported as a potential therapeutic agent for AD. However, its efficiency is reduced for AD patients due to its limited BBB permeability. Studies have demonstrated the feasibility of opening the blood-brain barrier (BBB) via focused ultrasound (FUS) to overcome the obstacles preventing medicines from blood flow into the brain tissue. We explored the therapeutic potential of FUS-mediated BBB opening combined with GAS in an AD-like mouse model induced by unilateral intracerebroventricular (ICV) injection of Aβ1-42. Mice were divided into 5 groups: control, untreated, GAS, FUS and FUS+GAS. Combined treatment (FUS+GAS) rather than single intervention (GAS or FUS) alleviated memory deficit and neuropathology of AD-like mice. The time that mice spent in the novel arm was prolonged in the Y-maze test after 15-day intervention, and the waste-cleaning effect was remarkably increased. Contents of Aβ, tau, and P-tau in the observed (also the targeted) hippocampus were reduced. BDNF, synaptophysin (SYN), and PSD-95 were upregulated in the combined group. Overall, our results demonstrate that FUS-mediated BBB opening combined with GAS injection exerts the potential to alleviate memory deficit and neuropathology in the AD-like experimental mouse model, which may be a novel strategy for AD treatment.