Protective effects of Zizyphus oxyphyla on liver and kidney related serum biomarkers in (CCl4) intoxicate rabbits

The study was aimed to evaluate the therapeutic effects of Zizyphus oxyphyla leaves methanolic (ZOX-LME), on serum liver, kidney and hematology along with other serum parameters in Carbon tetrachloride (CCl4) intoxicated rabbits. Experimental animals were divided into five groups, six rabbits in each. These were: group NC (normal control), group, TC (toxic control) and group ST i.e. silymarine administered group at dose rate (50) mg/kg body weight (BW). Group ET1 and group ET2 treated with (ZOX-LME) at dose 200 mg/kg BW and 400 mg/kg BW. CCl4 administration caused significant (P> 0.05) impairment in serum liver enzymes, blood factors and other serum indices. Treatment with (ZOX-LME) significantly (P<0.05) reduced and normalized the levels of serum alanine transaminase (ALT) aspartate transaminase (AST) and alkaline phosphatase (ALP) and hematological indices. Also significant (P< 0.05) reduction was observed in creatinine, urea, uric acid, blood urea nitrogen (BUN), and albumin and glucose concentrations. The altered levels of lipid profile and serum electrolytes (Ca, Mg, Cl, Na, K, and P) were significantly (P<0.05) change toward normal levels with (ZOX-LME) feeding. In addition (ZOX-LME) ingestion caused significant improvement in GSH, GST and CAT levels, while reducing the TBARS levels, exhibited antioxidant capacity. Also (ZOX-LME) showed increase inhibition against percent scavenging of 2, 2-diphenile-1-picrylehydrazyle (DPPH) free radical. Significant (P<0.05) normalizing effects were observed with high dose 400 mg/kg BW of (ZOX-LME and were equivalent to silymarine administered groups. The histological study of liver supported the hepatoprotective and renal curative activity of (ZOX-LME).

Toxicity evaluation of Dolichandrone serrulata flower extract on vital and reproductive organs in adult male rats

Although Dolichandrone serrulata flower (DSF) aqueous extract has been shown to possess pharmacological properties, its systemic toxicity has still to be evaluated. The present study aimed to investigate the sub-chronic toxicity effect of DSF extract on biochemical parameters and histological structures of liver, kidney, testis, and epididymis plus vas deferens. Adult male rats were administered DSF at 100, 300, and 600 mg/kgBW via oral gavage for 48 consecutive days while control rats received distilled water. At the end of the experiment, blood, liver, kidney, testis, and epididymis plus vas deferens samples were collected to determine any changes to serum biochemical components including ALT, ALP, and creatinine levels and histological structures. The results revealed no significant difference in body weight and food or water consumption between control and the DSF-treated groups. It was found that DSF significantly increases the weight of epididymis plus vas deferens, while the kidney and liver showed a decrease in the high dose group (P value < 0.05). Histological changes in these vital and reproductive tissues including fibrosis were not observed after administration but ALT, ALP, and creatinine levels were significantly altered in the treated groups (P value < 0.05). These altered levels, however, were still within normal ranges. In conclusion, these findings demonstrated that D. serrulata flower extract had no sub-chronic toxicity on vital and reproductive structures but slightly altered some liver and kidney functions.

Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse

The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Effects of Lycium barbarum polysaccharide on the photoinduced autophagy of retinal pigment epithelium cells

AIM: To investigate the relationship between autophagy and apoptosis in photoinduced injuries in retinal pigment epithelium (RPE) cells and how Lycium barbarum polysaccharide (LBP) contributes to the increased of RPE cells to photoinduced autophagy. METHODS: In vitro cultures of human RPE strains (ARPE-19) were prepared and randomly divided into the blank control, model, low-dose LBP, middle-dose LBP, high-dose LBP, and 3-methyladenine (3MA) groups. The viability of the RPE cells and apoptosis levels in each group were tested through cell counting kit-8 (CCK8) method with a flow cytometer (Annexin V/PI double staining technique). The expression levels of LC3II, LC3I, and P62 proteins were detected with the immunofluorescence method. The expression levels of beclin1, LC3, P62, PI3K, P-mTOR, mTOR, P-Akt, and Akt proteins were tested through Western blot. RESULTS: LBP considerably strengthens cell viability and inhibits the apoptosis of RPE cells after photoinduction. The PI3K/Akt/mTOR signal pathway is activated because of the upregulation of the phosphorylation levels of Akt and mTOR proteins, and thus autophagy is inhibited. CONCLUSION: LBP can inhibit the excessive autophagy in RPE cells by activating the PI3K/Akt/mTOR signaling pathways and thereby protect RPE cells from photoinduced injuries.

Efficacy and Safety of GHX02 in the Treatment of Acute Bronchitis and Acute Exacerbation of Chronic Bronchitis: A Phase Ⅱ, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

Acute bronchitis and acute exacerbations of chronic bronchitis (AECB) have cough and sputum as the main symptoms with a high prevalence and substantial economic burden. Although the demand for bronchitis treatment increases due to causes, such as air pollution, the appropriateness of antibiotic prescriptions and the effects of current symptomatic treatments for bronchitis are unclear. GHX02, which is a combined formulation containing four herbs, and has been clinically used for bronchitis in South Korea. We conducted a phase II, randomized, double-blind, and placebo-controlled, multicenter trial to evaluate its efficacy and safety. Patients with acute bronchitis or AECB were recruited and randomized to receive high-dose GHX02 (1920 mg/day), standard-dose GHX02 (960 mg/day), or placebo for 7 days. The primary outcome measure was the change in Bronchitis Severity Score (BSS) from baseline to Day 7. The secondary outcomes were the frequency of coughing fits, Questionnaire of Clinical Symptoms of Cough and Sputum (QCSCS), Leicester Cough Questionnaire (LCQ), Integrative Medicine Outcome Scale (IMOS), and Integrative Medicine Patient Satisfaction Scale (IMPSS). A total of 117 patients were randomized to parallel groups (38 in the high-dose GHX02, 41 in the standard-dose GHX02 group, and 38 in the placebo group). The mean differences in BSS from baseline to Day 7 in the treatment groups (4.2 ± 2.0 and 4.5 ± 1.8 in the high-dose GHX02 and standard-dose GHX02 groups, respectively) were higher than the placebo group (3.8 ± 2.1), p = 0.028. The mean differences in the frequency of coughing fits from baseline to Day 7 and IMPSS were better in the GHX02 treatment group than in the placebo group (standard-dose GHX02 group vs placebo group, p = 0.036). The QCSCS, LCQ, IMOS, and GHX02 of the treatment groups also showed more improvement than the placebo group, but there were no statistically significant differences between the groups. There were no severe adverse effects during the trial. This study supports that GHX02 is effective and safe for patients with bronchitis and provides the basis for progression to a phase III study.Clinical Trial Registration: [https://cris.nih.go.kr] WHO International Clinical Trials Registry Platform, Clinical Research Information Service [KCT0003665].

Paraneoplastic Neuromyelitis Optica Spectrum Disorder Associated With Lung Adenocarcinoma: A Case Report

Neuromyelitis Optica spectrum disorder is an inflammatory demyelinating disease affecting the central nervous system (CNS), characterized by triad optic neuritis, transverse myelitis, and area postrema syndrome. Antibodies directed against aquaporin-4 (AQP-4), a water channel expressed on the astrocytic membrane, are supposed to play a pathogenic role and are detected in ~80% of cases. Clinical signs of Neuromyelitis Optica spectrum disorder (NMOSD) in elderly patients should arouse the suspicion of paraneoplastic etiology. In this article, we discussed a case of a 76-year-old woman with a 2-month history of confusion, dysarthria, and progressive bilateral leg weakness. A whole-body CT scan showed a neoformation of 5 cm in diameter in the median lobe infiltrating the mediastinal pleura. The tumor had already spread to both the upper and lower right lobes, parietal pleura, and multiple lymph nodes. Pleural cytology revealed adenocarcinoma cells. The brain MRI documented hyperintense alteration in fluid-attenuated inversion recovery (FLAIR) images, involving the anterior portion of the corpus callosum and the periependymal white matter surrounding the lateral ventricles, with mild contrast enhancement on the same areas and meningeal tissue. T2-weighted spinal cord MRI sequences showed extended signal hyperintensity from bulbo-cervical junction to D7 metamer, mainly interesting the central component and the gray matter. Cerebrospinal fluid analysis revealed no neoplastic cells. Serum AQP-4 immunoglobulin (IgG) antibodies were found. Meanwhile, the patient rapidly developed progressive paraparesis and decreased level of consciousness. High-dose intravenous methylprednisolone therapy was started but her conditions rapidly deteriorated. No other treatment was possible.

Different Doses of Calcium Supplementation to Prevent Gestational Hypertension and Pre-Eclampsia: A Systematic Review and Network Meta-Analysis

ObjectiveCalcium supplementation can prevent gestational hypertension and pre-eclampsia. However, besides the non-consensus of existing studies, there is a lack of evidence regarding the optimal dosing of calcium.MethodEight electronic databases, namely, the Cochrane Library, PUBMED, Web of Science, EMBASE, WANGFANG, VIP, CBM, and CNKI, were searched. The studies were retrieved from inception to July 13, 2021. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality based on the inclusion criteria. In particular, the calcium supplementation doses were divided into three groups, namely, the high-dose (≥1.5 g), medium-dose (1.0–1.49 g), and the low-dose group (&lt;1.0 g). The participants were also divided into high-risk and low-risk groups, according to the risk of developing gestational hypertension and pre-eclampsia.Results and DiscussionA total of 48 studies were incorporated into the final analyses. All doses of calcium supplementation reduced the incidence of gestational hypertension in the low-risk population (low dose - three studies; medium dose- 11 studies; high dose- 28 studies), whereas the medium-dose (three studies) reduced the incidence of gestational hypertension in high-risk groups. Moreover, a medium dose of calcium supplementation had the maximum effect in reducing gestational hypertension in low-risk and high-risk populations. The medium (three studies) and high doses (13 studies) of calcium supplementation reduced the incidence of pre-eclampsia in the low-risk groups. However, a medium-dose calcium supplementation maximally prevented pre-eclampsia in the low-risk population. The authenticity and reliability of the results were reduced due to the limitations of contemporary studies in terms of experimental design, result measurement, statistics, and evidence quality. Therefore, high-quality studies with larger sample size are required to evaluate further the effect of calcium supplementation in preventing gestational hypertension and pre-eclampsia.