A comprehensive review of ethnomedicinal approaches, phytochemical analysis, and pharmacological potential of Vitex trifolia L.

Plants, renowned for their rich reservoir of metabolites, play a pivotal role in addressing health-related issues. The Verbenaceae family stands out, showcasing immense potential in preventing and treating chronic diseases. Vitex trifolia L. (V. trifolia), a shrub with a rich history in traditional medicine, particularly in Eastern Asia, has garnered attention for its diverse therapeutic applications. This comprehensive review aims to bridge traditional knowledge and contemporary insights by investigating ethnopharmacology, phytochemistry, and pharmacological effects of V. trifolia. The keyword "V. trifolia" and its synonyms were searched within the main scientific databases including PubMed, Web of Science, ScienceDirect, Google Scholar, and Baidu Scholar (from 1974 to 2022, last search: 21.10.2023). Phytochemical analyses reveal a spectrum of secondary metabolites in V. trifolia, including terpenoids, flavonoids, lignans, phytosterols, anthraquinones, and fatty acids. Notably, terpenoids and flavonoids emerge as the main bioactive metabolites. Pharmacological studies validate its therapeutic potential, demonstrating significant antioxidant, anti-inflammatory, hepatoprotective, anticancer, anti-amnesic, antimicrobial, antiviral, anti-malaria, antispasmodic activities, and reported insecticidal effects. Despite existing literature exploring pharmacological attributes and secondary metabolites of related species, a conspicuous gap exists, specifically focusing on the pharmacological activities and novel methods of purification of pure metabolites from V. trifolia. This review aimed to fill this gap by delving into traditional medicinal applications, exploring secondary metabolites comprehensively, and providing an in-depth analysis of pharmacological effects of pure metabolites. Combining traditional uses with contemporary pharmacological insights, this article sought to serve as a crucial reference for future research and practical application of V. trifolia. This approach contributes substantially to understanding the plant, fostering scientific inquiry, and facilitating its broader application in healthcare.

Melatonin and metformin co-loaded nanoliposomes efficiently attenuate liver damage induced by bile duct ligation in rats.

In the current study, the therapeutic effectiveness of the metformin (Met) and melatonin (Mel) co-loaded liposomes was investigated on cholestasis induced by bile duct ligation (BDL) in male rats. Histopathological analysis, biochemical analysis, and oxidative stress markers were assayed to determine the therapeutic effect of Met and Mel co-loaded liposomes on cholestasis. Histopathological analysis revealed that the simultaneous administration of Met and Mel, whether in the free (C-Mel-Met) or liposomal (C-Lipo-Mel-Met) forms, reduced inflammation as well as proliferation of bile ducts; however, results were more prominent in the liposomal form of Mel and Met. Additionaly, serum levels of aspartate aminotransferase (AST) were significantly (p < 0.001) higher in (C-Mel-Met) treated rats compared with (BDL) rats; however, (C-Lipo-Mel-Met) treated rats exhibited significant (p < 0.05) lower AST rates in comparison to (BDL) rats. Moreover, a significant (p < 0.0001) drop in bilirubin levels was detected in (C-Lipo-Mel-Met) treated rats in comparison to (BDL) rats; it is noteworthy mentioning that bilirubin levels in (C-Lipo-Mel-Met) treated rats were insignificant in comparison to sham-control (SC) rats. Furthermore, rats concomitantly administered Met and Mel, exhibited significant downregulation in the expression levels of inflammatory cytokine genes such as TNF-α and IL-1 gene expression, where the downregulation was more prominent in the liposomal from. Our findings demonestrate that the concomitant administration of metformin and melatonin in the liposomal form had more therapeutic effect on liver injury than their free forms through improving histological changes, reducing biochemical markers and favoring oxidant- antioxidant balance.

The Alleviating Impacts of Quercetin on Inflammation and Oxidant-antioxidant Imbalance in Rats with Allergic Asthma.

Asthma is an inflammatory disease of the airways. We assessed the anti-inflammatory and antioxidative impacts of quercetin, a plant derivative, on inflammatory and oxidative indices in lung tissue and serum of rats with asthma.Asth ma was induced by ovalbumin. Rats were divided into 4 groups: control, asthma+vehicle (Receieved normal saline), asthma+dexamethasone, and asthma+quercetin. After asthma induction, quercetin (50 mg/kg) and dexamethasone (2.5 mg/kg) were injected intraperitoneally once daily for 1 week. On day 50, lung histopathology indices; inflammatory factors; tissue gene expression, including GATA Binding Protein 3 (Gata-3), Tbx21 (T-bet), Transforming growth factor-ß (TGF-ß), Il10 (IL-10), Il1b (IL-1ß), Il6 (IL-6), Acta2 (α-SMA), and Tnf (TNF-α); and oxidative stress indices (malondialdehyde [MDA], catalase [CAT], glutathione peroxidase [GPX], superoxide dismutase [SOD], and total antioxidant capacity [TAC]) in tissue and serum, were evaluated. The results showed that quercetin reduced Gata3, Tnf, Tgfb1, Il1b, and Acta2 gene expression and increased Tbx21 gene expression following asthma. Quercetin also improved oxidative stress by decreasing MDA levels and increasing TAC, CAT, SOD, and GPX levels in serum and lung tissue. Furthermore, quercetin decreased IL6 and TNFα levels and increased IL10 levels in lung tissue after asthma was treated with quercetin. Quercetin ameliorates oxidative stress and inflammation caused by asthma, especially at the tissue level. Therefore, quercetin can be considered a potent antiasthmatic agent.

Melatonin-Attenuated Oxidative Stress in High-Risk Pregnant Women Receiving Enoxaparin and Aspirin.

Objective: In pregnancy, reducing inflammation and oxidative stress is important. Administration of melatonin during pregnancy can improve reproductive performance by improving the placental antioxidant system and inflammatory response. This investigation was carried out to evaluate the beneficial impact of melatonin on the oxidative stress state among high-risk pregnant women receiving enoxaparin and aspirin. Methods: In this double-blind, placebo-controlled trial, 40 pregnant women, aged 15-45 years at 6 weeks of pregnancy, were randomly selected and divided into intervention and control groups. The control group received prophylaxis enoxaparin and aspirin once daily between 6 and 16 weeks of pregnancy. The intervention group was taken enoxaparin and aspirin for 9 weeks and melatonin once daily from the sixth week of pregnancy to delivery time. Blood samples were taken to measure some oxidative stress biomarkers including total antioxidant capacity (TAC), malondialdehyde (MDA), total thiol (T-SH), protein carbonyl (PCO), and nitric oxide (NO). The level of high-sensitivity C-reactive protein (hs-CRP) was also determined. Results: TAC and T-SH levels increased significantly in the intervention group in comparison with the control group. Melatonin administration compared to the control group led to a significantly decreased level of NO and an insignificant hs-CRP level. Conclusion: Melatonin supplementation in high-risk pregnancy had favorable effects on TAC, T-SH, NO, and hs-CRP levels, improved antioxidant activity, and reduced inflammation. More studies are needed in different pregnancy conditions along with the measurement of different biomarkers.

Renoprotective effects of zinc sulfate against transient liver ischemia/reperfusion injury in rats.

Objectives: Liver ischemia/reperfusion damage frequently occurs in setting of hepatic resection and liver transplantation. It leads to disturbance in remote organs such as heart, lung and kidneys. This study explored the consequences of hepatic ischemia/reperfusion on the oxidative stress parameters, biochemical factors, and histopathological alterations in the kidney's rats, as well as evaluated the role of zinc sulfate on above-mentioned parameters. Materials and methods: Twenty-eight male Wistar rats were accidently assigned into four groups (n = 7). They were Sham, ischemia/reperfusion, zinc sulfate pretreatment, and zinc sulfate pretreatment + ischemia/reperfusion groups. Sham group: obtained normal saline (2 ml/day, seven consecutive days), intraperitoneally, zinc sulfate pretreatment group: obtained zinc sulfate (5 mg/kg, seven consecutive days, intraperitoneally). Ischemia/reperfusion group: obtained normal saline as mentioned previous, then rats experienced the partial ischemia (%70) for 45 min followed by 60 min reperfusion. Zinc sulfate pretreatment group: obtained zinc sulfate as mentioned previous, then rats experience the partial ischemia/reperfusion as presented earlier. At the end of investigation, blood was withdrawn, liver and renal tissues were removed. Then, biochemical and oxidative stress parameters, and histological changes were evaluated in the mentioned tissues. Results: The findings of this experiment indicated that zinc sulfate markedly reduced the serum levels of liver and kidney function tests in relative to ischemia/reperfusion group. Also, antioxidant enzymes activity, ferric reducing antioxidant power, and nitric oxide significantly increased, while malondialdehyde level declined in the renal tissue of zinc sulfate + ischemia/reperfusion group compared to ischemia/reperfusion rats. Furthermore, zinc sulfate alleviated the liver and kidneys histopathological alterations following ischemia/reperfusion. Conclusion: Zinc sulfate ameliorated liver and kidney function, and improved oxidant-antioxidant balance in favor of antioxidants. It is suggested that zinc sulfate may be beneficial effects on hepato-renal injury after ischemia/reperfusion.

Combined treatment with Alhagi maurorum and docetaxel inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vivo.

Breast cancer is a challenging disease and leading cause of cancer death in women. There is no effective agent for metastatic breast cancer after surgery and chemotherapy. Alhagi maurorum (A.m) has been reported to exhibit an anticancer effect on various types of cancer cells in vitro. This study aimed to examine the suppressive effect of A.m alone and combined with docetaxel (DTX) on the breast cancer growth in mice models and the possible underlying mechanisms. In the present study, the mice were inoculated subcutaneously with the injections of 4T1 cells. Then, A.m, DTX, and their combination were administered intraperitoneally. The expressions of ß-catenin (ß-cat), FZD7, MMP2, HIF1-α, and VEGF A (vascular endothelial growth factor A) were investigated using RT-PCR method. Also, plasma alkaline phosphatase (ALP), alanine aminotransferase (GPT or ALT), aspartate transaminase (GOT or AST), serum creatinine, and urea were examined, and histological analyses of the tissues were conducted. The results demonstrated that A.m (500 mg/kg) combined with DTX significantly decreased the expression of ß-cat, MMP2, and FZD7 as compared with the negative control group and monotherapies. Also, the mRNA levels of HIF1-α and VEGF A were suppressed significantly by DTX + A.m (500 mg/kg). Tumor weights and sizes were significantly lower and tumor inhibition rate was significantly higher in the DTX + A.m group. The A.m 500 mg/kg + DTX also suppressed the serum GPT level in tumor-bearing mice and decreased the serum urea level. Taken together, our findings suggest that DTX combined with A.m at an optimal dose of 500 mg/kg as the optimal dose can inhibit ß-cat, FZD7, MMP2, and breast cancer growth via interrupting HIF-1α/VEGF signaling and might be used as a promising antiangiogenic agent for breast cancer treatment.

In vitro and Molecular Docking Analysis of Quercetin as an Anti-inflammatory and Antioxidant.

INTRODUCTION: Quercetin (3,3',4',5,7-pentahydroxyflavone) is a dietary flavonoid with good antioxidant and anti-inflammatory properties. AIMS: The present study aims to determine these effects in peripheral blood mononuclear cells (PBMCs) evoked by lipopolysaccharides (LPS). METHODS: The mRNA expression and protein secretion of inflammatory mediators were evaluated by enzyme- linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (PCR), respectively. Western blotting was utilized for assessing p65-NF-κB phosphorylation. Ransod kits evaluated the glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity in the cell lysates. Ultimately, the molecular docking approach was performed to investigate the biological activity of Quercetin against NF-κB pathway proteins and antioxidant enzymes. RESULTS: The findings revealed that quercetin significantly attenuated the expression and secretion of inflammatory mediators and p65-NF-κB phosphorylation in LPS-induced PBMCs. Additionally, quercetin dose-dependently improved the activities of SOD and GPx enzymes and decreased LPS-mediated oxidative stress in PBMCs. Moreover, quercetin has a considerable binding affinity to IκKb, the core element of the NF-κB pathway and the antioxidant enzyme SOD. CONCLUSION: The data show that quercetin plays a vital role in ameliorating inflammation and oxidative stress caused by LPS in PBMCs.

Effect of metformin on the long non-coding RNA expression levels in type 2 diabetes: an in vitro and clinical trial study.

BACKGROUND: It has been suggested that the anti-hyperglycemic effect of metformin could be associated with its impact on long non-coding RNA (lncRNA) expression levels. Accordingly, in the current study, we evaluated the effect of metformin on the expression of H19, MEG3, MALAT1, and GAS5 in in vitro and in vivo situations. METHODS: The effect of hyperglycemia and metformin treatment on the lncRNAs expression level was evaluated in HepG2 cells. A total of 179 age- and sex-matched subjects, including 88 newly diagnosed patients with type 2 diabetes (T2D) and 91 healthy volunteers, were included in the case-control phase of the study. Moreover, 40 newly diagnosed patients participated in the study's open-labeled non-controlled clinical trial phase. The expression levels of lncRNA in HepG2 cells and whole blood samples were determined using QRT-PCR. RESULTS: In vitro results showed that hyperglycemia induced H19 and MALAT1 and decreased GAS5 expression levels. Moreover, metformin decreased H19 and increased GAS5 expression in high glucose-treated cells. Case-control study findings revealed that the circulating levels of H19, MALAT1, and MEG3 were significantly elevated in T2D patients compared to the control subjects. Finally, results showed that the level of circulating H19 levels decreased while GAS5 increased in T2D patients after taking metformin for 2 months. CONCLUSION: The results of the current study provided evidence that metformin could exert its effect in the treatment of T2D by altering the expression levels of H19 and GAS5.

Empagliflozin Exhibits Hepatoprotective Effects Against Bile Duct Ligation-induced Liver Injury in Rats: A Combined Molecular Docking Approach to In Vivo Studies.

BACKGROUND: Cholestatic liver damage is a chronic disease caused by dysfunction of the hepaticbiliary system. Oxidative stress and inflammation are essential factors in the pathogenesis of cholestasis. Thus, the current study was designed to examine the effect of empagliflozin on bile duct ligation-induced liver damage in rats. METHODS: This study was done on male Wistar rats, which were randomly assigned to the four experimental groups: sham control (SC), bile duct ligation (BDL), SC plus empagliflozin (SC+EMPA) (receiving 10 mg of EMPA orally for 7 days), BDL plus empagliflozin 10 mg/kg (BDL+ EMPA). At the end of the study, the rats were sacrificed, and serum and tissue samples were collected to analyze biochemical parameters, biomarkers of oxidative stress, inflammatory markers, and histopathological changes. The molecular docking technique was performed to elucidate the interaction of EMPA and Cu/Zn-superoxide dismutase (SOD1). RESULTS: The results showed that BDL elevated the serum activity of ALT, AST, ALP, and levels of TBIL and TPro. BDL also intensifies the oxidative stress state in rats, which was confirmed by augmenting lipid peroxidation (MDA), protein oxidation (PCO), and altering antioxidant defense parameters through decreased SOD, catalase (CAT), and glutathione peroxidase (GPX) levels. Furthermore, the histopathological changes in the liver demonstrated the aggravation of inflammation and oxidative stress. In contrast, treatment with EMPA has shown anti-inflammatory and anti-oxidant effects by reducing TNF-α and IL-6 pro-inflammatory marker proteins, restoring the antioxidant status (increased SOD and GPX), reducing ALT, AST, ALP, TBIL levels, and protein oxidation, and improving the histopathological alterations through reducing bile duct proliferation, fibrosis, focal and portal inflammation. According to the attained findings, the SOD1 activity can be regulated by the EMPA. Our documentation presents direct evidence at the molecular level related to the ability of EMPA to exert its antioxidant performance through certain measures in a particular molecular route. CONCLUSION: The results showed EMPA to have hepatic protective effects in rats against cholestatic liver injury, an effect mediated by its antioxidant and anti-inflammatory properties.

The Hydroalcoholic Extract of Nasturtium officinale Reduces Lung Inflammation and Oxidative Stress in an Ovalbumin-Induced Rat Model of Asthma.

Background: Asthma is known as a disease that causes breathing problems in children and adults and is also associated with chronic inflammation and oxidative stress of the airways. Nasturtium officinale (NO) possesses a wide range of pharmacological properties, particularly anti-inflammation and antioxidant potentials. Thus, this study for the first time was aimed to investigate anti-inflammatory and antioxidative activities of NO extract (NOE) in an ovalbumin-induced rat model of asthma. Materials and Methods: Forty-four male Wistar rats were sensitized with ovalbumin (OVA) to induce asthma symptoms. The animals were allocated into five groups: control (C), asthmatic (A), A + NOE (500 mg/kg), NOE (500 mg/kg), and A + dexamethasone (DX, 2.5 mg/kg). After 7 days, blood and tissue samples were taken from the rats. Then, the level of inflammatory markers, oxidative stress parameters, and antioxidant enzymes activity were measured. Results: The obtained results showed that OVA-sensitive rats significantly increased the levels of pro-inflammatory cytokines IL-1B, TGF-ß, and SMA-α compared to the control group (p < 0.05), while treatment with NOE remarkably reduced the SMA-α gene expression compared to the asthma group (p < 0.05). Furthermore, it decreased the expression of IL-1B and TNF-α genes, although it was not statistically significant. The level of glutathione peroxidase (GPX) significantly reduced in A group compared to the C group (p < 0.05), whereas NOE administration significantly increased this marker (p < 0.05). Moreover, NOE attenuated inflammation and alveolar injury in the lungs of OVA-sensitive rat compared to the nontreated A group. Conclusions: Overall, our findings demonstrated that NOE somewhat is able to reduce airway inflammation by reducing inflammatory and increasing GPX activity. Indeed, further experiments investigating the impact of different extract doses are needed to confirm the antioxidant and anti-inflammatory effects of NOE.

Stachys pilifera Benth: A Review of Its Botany, Phytochemistry, Therapeutic Potential, and Toxicology.

Background: Stachys L. (Lamiaceae) includes more than 300 annual or perennial species growing in temperate regions of Southern Africa, the Mediterranean, America, and Asia. Stachys pilifera Benth (S. pilifera), also known as Marzeh Kuhi, is an endemic species from Iran. It is found in the mountainous habitats of the Zagros area. It has various traditional uses, and the phytochemical ingredients and some biological activities of this species have been examined in previous studies. Methods: PubMed, Science Direct, Google Scholar, Scopus, and Science Web databases were used to gather the data. The purpose of this review is to consolidate the scattered knowledge reported in the literature about botany, traditional uses, phytochemistry, pharmacological properties, and safety of S. pilifera and suggest its potential medicinal properties. Key Findings. In traditional Iranian medicine, S. pilifera manages various illnesses, such as rheumatoid arthritis, common cold, infections, asthma, and tussive. More than 30 compounds have been identified in S. pilifera essential oil. The compounds found in S. pilifera are phenolic compounds, monoterpenes, sesquiterpenes, flavonoids, alkaloids, and terpenoids, which have various properties such as antioxidant, nephroprotective, anti-inflammatory, antimicrobial, hepatoprotective, and anticancer properties. Conclusions: The literature reveals that S. pilifera is an essential source of bioactive phytochemicals and illustrates the unknown area of this plant for new investigations. Moreover, we recommend that future research focus on toxicology and quality control studies for S. pilifera to fill the knowledge gap and provide theoretical support for the plant's possible functional and clinical uses.

A comparative study on the effect of blood collection tubes on stress oxidative markers.

Oxidative stress has a major role in disease pathogenesis. However, limited studies have investigated the effect of various sample collection tubes on oxidative biomarkers. The present study aimed to evaluate the effect of different collection tubes on the variation of malondialdehyde (MDA), nitric oxide (NO), total thiol (t-SH), and ferric reducing ability of plasma (FRAP) levels. A total of 35 individuals participated in this study and each collected sample was separated into three different tubes: glass tubes (GTs), plain plastic tubes (PTs), and gel separator tubes (GSTs). The results of PTs and GSTs were compared to those of GTs as the reference tube. The comparison between the means of biomarkers in various tubes indicated that there was no significant difference in MDA results between tubes. In contrast, t-SH and NO content were significantly decreased in GSTs and PTs compared to GTs. However, the Bland-Altman analysis showed an acceptable concordance for the mentioned analytes and the statistically significant differences were not clinically significant for NO, MDA, and t-SH antioxidant parameters. Moreover, the FRAP level was considerably lower in GSTs compared to GTs. Nevertheless, the Bland-Altman analysis showed a high bias percentage for the FRAP assay when using PTs and GSTs. According to the present results, it can be concluded that switching to plastic blood collection tubes or serum separation tubes could influence the FRAP results. However, there was no interference for the interpretation of other antioxidant assays in different types of collection tubes. Hence, it is suggested to use GTs for total antioxidant capacity evaluations, especially the FRAP assay.

Evaluation of the Antioxidant and Anticancer Activities of Hydroalcoholic Extracts of Thymus daenensis Celak and Stachys pilifera Benth.

Herein, the effects of hydroalcoholic extracts of Thymus daenensis Celak (TDC) and Stachys pilifera Benth (SPB) plants on HepG2 cell line were investigated by using different analyses. Cytotoxicity and apoptosis of extracts were investigated by MTT method, AnnV/PI apoptosis assay, and their antioxidant capacity was evaluated by total thiol and glutathione peroxidase (GPX) assay. The results revealed that the SBP extract was more cytotoxic compared with the TDC extract and increased over time (128.49 µg/mL vs 107.11 µg/mL IC50 values for 24 and 72 h, respectively). Although, AnnV/PI apoptosis assay showed apoptosis induction for both extracts, but the caspase-3 activity assay revealed that TDC extract significantly increased caspase-3 activity compared with the control and SPB extract. Increasing the activity of GPX by SPB extract revealed that it has high antioxidant capacity. In conclusion, the TDC and SPB with high antioxidant capacity have high cytotoxicity against HepG2 cancer cells and have high capability as a medicinal plant.

The Promising Therapeutic and Preventive Properties of Anthocyanidins/Anthocyanins on Prostate Cancer.

As water-soluble flavonoid derivatives, anthocyanidins and anthocyanins are the plants pigments mostly rich in berries, pomegranate, grapes, and dark color fruits. Many bioactivity properties of these advantageous phytochemicals have been reported; among them, their significant abilities in the suppression of tumor cells are of the promising therapeutic features, which have recently attracted great attention. The prostate malignancy, is considered the 2nd fatal and the most distributed cancer type in men worldwide. The present study was designated to gather the preclinical and clinical studies evaluating potencies of anthocyanidins/anthocyanins for the treatment and prevention of this cancer type for the first time. In general, findings confirm that the anthocyanins (especifically cyanidin-3-O-glucoside) indicated higher activity against prostatic neoplasms compared to their correlated anthocyanidins (e.g., delphinidin); in which potent anti-inflammatory, apoptosis, and anti-proliferative activities were analyzed. Complementary anti-prostate cancer assessment of diverse naturally occurred anthocyanidins/anthocyanins and their synthetically optimized derivatives through preclinical experiments and eventually confirmed by clinical trials can promisingly lead to discover natural-based chemotherapeutic drug options.

The Protective Effects of Securigera securidaca Seed Extract on Liver Injury Induced by Bile Duct Ligation in Rats.

This study is aimed at evaluating the effects of Securigera securidaca (SS) seed extract on cholestatic liver injury induced by bile duct ligation (BDL) in rats. Total polyphenols and flavonoids in SS seed extract were determined using a colorimetric assay, and their components were quantified using HPLC. Rats in four groups underwent BDL at the common bile duct and were treated for 21 days with either oral distilled water as vehicle, vitamin C, 100 mg/kg SS seed extract, or 200 mg/kg SS seed extract. Rats in the fifth group underwent abdominal incision without BDL and were treated with distilled water, and rats in the sixth group were healthy and received nothing. Finally, rats were sacrificed, blood samples were analyzed through biochemical methods, liver tissues were histologically assessed, and the expression of the TGFß-1, iNOS, caspase-3, and α-SMA genes in the liver was assessed through real-time PCR. BDL significantly increased, and SS seed extract significantly decreased the serum levels of bilirubin and liver function enzymes. Moreover, SS seed extract suppressed the expression of the TGFß-1, iNOS, caspase-3, and α-SMA genes, reduced the levels of nitric oxide, malondialdehyde, and protein carbonyl, and increased the levels of glutathione, total antioxidant capacity, and SOD and catalase enzyme activity in the serum and liver. Extract at a dose of 100 mg/kg had significant positive effects on liver morphology and parenchyma structure in a dose-dependent manner.

Prevalence of Proteinuria and Hematuria in a Rural Population in the Southwest of Iran.

Acute and chronic kidney diseases are common and are associated with the risk of kidney failure. Early detection of these disorders prevents their progression to kidney damage in later stages. The aim of this study was to investigate the prevalence of proteinuria and hematuria in a rural population in Yasuj, Iran. In this cross-sectional study, 676 people (350 females and 326 males) participated. People with positive dipstick test results entered the second screening and the urinary protein-to-creatinine ratio (UPCR) was measured. People with UPCR ≥150 mg/g were evaluated for demographic and biochemical indicators. In the initial screening, 72 subjects (10.6%) tested positive by the dipstick test with trace proteinuria or higher. The UPCR results showed that this ratio was above 150 mg/g in 42 patients (6.2%), which was approximately equivalent to more than 150 mg of protein excreted per day. There was no significant relationship between the prevalence of proteinuria and the demographic and biochemical markers. Briefly, it seems that the prevalence of proteinuria found by the dipstick test was similar to that in other parts of the world. However, according to the UPCR index, the percentage of proteinuria was significantly higher than in other studies. Because of the unknown mechanism of proteinuria, more studies based on genetic tests and kidney biopsies are needed to determine the causes of proteinuria.

Association between circulating visfatin and pre-eclampsia: a systematic review and meta-analysis.

OBJECTIVE: Pre-eclampsia (PE) is a serious pregnancy status characterized by high blood pressure. Although visfatin is usually associated with PE. Observational studies evaluating the relationship between circulating visfatin and pre-eclampsia have reported inconsistent results. We conducted this systematic review and meta-analysis to summarize published data on the association between visfatin and pre-eclampsia. METHODS: Electronic databases PubMed, ISI web of science, EMBASE, Scopus and the Cochrane library were comprehensively searched for selection of eligible studies until January 5, 2020. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. The assessment of study quality was performed using the e Newcastle-Ottawa scale and the Agency for Healthcare Research and Quality. Sensitivity analyses and prespecified subgroup were conducted to evaluate potential heterogeneity. Random-effects meta-regression was conducted to assess the impact of potential confounders on the estimated effect sizes. The protocol for this study was registered in PROSPERO (No. CRD42018105861) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Thirteen studies comprising a total of 536 subjects were included in this meta-analysis. We observed that the pre-eclampsia risk is associated with a statistically significant elevation of visfatin level [SMD (1.33 µg/l) (95% CI 0.37, 2.2) p = .007]. No significant publication bias was observed in the meta-analysis. Subgroup and sensitivity analyses indicated that the pooled effects size were affected by systolic blood pressure [SMD (1.82 µg/l) 95% CI (0.94, 2.7), p < .05], gestational age [SMD (2.01 µg/l) 95% CI (0.57, 3.4), p = .006], body mass index [SMD (1.6 µg/l) 95% CI (0.37, 3), p < .05] and pregnancy trimesters[SMD (2.3 µg/l) 95% CI (0.95, 3.7), p = .001]. Random-effects meta-regression showed a significant association of visfatin level with potential confounders including systolic blood pressure, gestational age and birth weight at delivery of pre-eclampsia patients. CONCLUSIONS: Collectively, our data revealed that the increase of visfatin level can be associated with the risk of pre-eclampsia. However, further studies on pre-eclampsia populations are warranted for corroboration of our findings.

Fluvoxamine ameliorates oxidative stress and inflammation induced by bile-duct ligation in male rats.

Introduction: Cholestasis is a disorder that the bile ducts were narrowed and bile acids are not released simply. Bile acids-induced liver damage is exacerbated by inflammation and oxidative stress. The goal of the current study was to investigate the protective impacts of fluvoxamine (Flu) on oxidant-antioxidant balance and inflammatory cytokines in the bile duct ligated (BDL) rats. Methods: Thirty-two male rats were arbitrarily allocated in 4 groups; sham-control (SC), SC+ 150 mg/kg Flu (SCF), bile duct ligation (BDL), and BDL+ 150 mg/kg Flu (BDLF). The rats received distilled water and Flu orally for one week. Biochemical analysis, hematoxylin and eosin staining, as well as oxidant/antioxidant status were evaluated. Also, the mRNA expression of TGF-ß1, IL-1, TNF-α, and α-SMA were determined. Results: The findings indicated serum values of ALT, total bilirubin, and ALP slightly declined in the BDL + Flu group in contrast to BDL rats. The plasma protein carbonyl and inflammatory markers were markedly increased in the BDL group in contrast with SC group (P ≤ 0.05). Treatment with Flu in BDL rats markedly reduced the values of hepatic nitric oxide metabolite and malondialdehyde, plasma protein carbonyl, as well as TNF-α mRNA level (P ≤ 0.05). Histological parameters were improved in the BDL + Flu group in comparison to BDL merely rats. Conclusion: It seems that Flu declined oxidative stress probably by inhibiting lipid peroxidation, protein oxidation, and nitric oxide formation. Also, it reduced inflammation by decreasing TNF-α mRNA expression.

Trehalose and N-Acetyl Cysteine Alleviate Inflammatory Cytokine Production and Oxidative Stress in LPS-Stimulated Human Peripheral Blood Mononuclear Cells.

BACKGROUND: Evidence has shown that inflammation and oxidative stress are implicated in the development of a great number of human diseases. Trehalose possesses various biological effects including antioxidant and anti-inflammatory activities. However, there is little data on the effects of trehalose on human cells including peripheral blood mononuclear cells (PBMCs). Here, we aimed to investigate whether trehalose could attenuate oxidative stress and inflammation induced by lipopolysaccharides (LPS) in PBMCs. METHODS: The enzyme-linked immunosorbent assay (ELISA) and RT-PCR were used to assess the levels of inflammatory cytokines. To investigate the phosphorylation of c-Jun N-terminal kinase (JNK) and NF-κB, western blot analysis was utilized. Oxidant-antioxidant markers were assessed using ELISA and colorimetric procedures. RESULTS: The results revealed that trehalose significantly mitigated the effect of LPS on the phosphorylation of JNK and NF-κB-P65 (p < .00). This mitigation was associated with significantly reduced levels of inflammatory cytokines IL-6, TNF-α, and IL-1ß and increased levels of anti-inflammatory cytokine IL-10 (P < .05). The antioxidant N-acetyl cysteine (NAC) also showed similar effects on JNK and NF-κB-P65 phosphorylation and inflammatory cytokines (p < .00). Furthermore, trehalose alleviated oxidative stress in LPS-stimulated PBMCs as it reversed the altered levels of malondialdehyde and total thiols (p ≤ .05) and restored the activity of antioxidant enzymes glutathione peroxidase and manganese superoxide dismutase (p < .001). CONCLUSION: The results of this study indicated that trehalose prevented inflammation and oxidative stress in the LPS-stimulated PBMCs, providing evidence for the benefits of trehalose as a potential therapeutic agent in inflammatory conditions. ABBREVIATIONS: LPS: Lipopolysaccharide; NAC: N-Acetyl cysteine; ROS: Reactive oxygen species; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha; SOD: Superoxide dismutase; GPx: Glutathione peroxidase; MDA: Malondialdehyde; MAPK: Mitogen-activated protein kinases; JNK: c-Jun N-terminal kinase; NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B cells.

Acute Secondary Adrenal Insufficiency Misdiagnosed as Acute Cholecystitis.

Hypopituitarism refers to insufficient secretion of the pituitary hormones. Patients with acute adrenocorticotropic hormone (ACTH) deficiency may be presented with fatigue, dizziness, orthostatic hypotension, hypoglycemia, nausea, vomiting, or nonspecific abdominal pain. This study described an unusual case of hypopituitarism in a patient who presented with general abdominal pain, abdominal tenderness, nausea, vomiting, hypotension, and hypoglycemia. At first, the patient was admitted with the diagnosis of acute cholecystitis, but after treatment of hypopituitarism and adrenal insufficiency, his symptoms resolved completely, without the need for surgery. Hypopituitarism and secondary adrenal insufficiency should be considered in the differential diagnosis of the patients who present with acute abdomen, hypotension, or hypoglycemia.