Interplay between proteasome inhibitors and NF-κB pathway in leukemia and lymphoma: a comprehensive review on challenges ahead of proteasome inhibitors.

The current scientific literature has extensively explored the potential role of proteasome inhibitors (PIs) in the NF-κB pathway of leukemia and lymphoma. The ubiquitin-proteasome system (UPS) is a critical component in regulating protein degradation in eukaryotic cells. PIs, such as BTZ, are used to target the 26S proteasome in hematologic malignancies, resulting in the prevention of the degradation of tumor suppressor proteins, the activation of intrinsic mitochondrial-dependent cell death, and the inhibition of the NF-κB signaling pathway. NF-κB is a transcription factor that plays a critical role in the regulation of apoptosis, cell proliferation, differentiation, inflammation, angiogenesis, and tumor migration. Despite the successful use of PIs in various hematologic malignancies, there are limitations such as resistant to these inhibitors. Some reports suggest that PIs can induce NF-κB activation, which increases the survival of malignant cells. This article discusses the various aspects of PIs' effects on the NF-κB pathway and their limitations. Video Abstract.

The effect of curcumin on hypoxia in the tumour microenvironment as a regulatory factor in cancer.

Hypoxia can lead to different responses from cancer cells, including cell death or survival, partially depending on how long it is exposed. Patients with cancer and under hypoxic tumour conditions have a poorer prognosis and are at greater risk of metastasis. Physiological response to low oxygen levels is controlled by hypoxia-inducible factor (HIF)-1. Curcumin, the major component of the rhizomes of Curcuma longa L., reduces HIF-1 levels and function, inhibiting the production of vascular endothelial growth factor (VEGF). In addition, curcumin efficiently inhibits the angiogenesis of vascular endothelial cells triggered by hypoxia. One of the most compelling features that drive continued interest in curcumin is the molecules' modulation of initiation, promotion, and progression stages of cancer while concomitantly acting as a radiosensitizer and chemosensitizer for tumours. In this review, we discuss the role of curcumin in modulating hypoxia and investigate the mechanisms and regulatory factors of hypoxia in tumour tissues.

Higher Risk of Chronic Hepatitis E Virus Infection in Patients with Human Immunodeficiency Virus-1: An Iranian Cross-sectional Study.

Background & Objective: Occurrence of Hepatitis E Virus (HEV) infection may be common in Human Immunodeficiency Virus (HIV-1) patients and may lead to chronic infection as well as cirrhosis. We intended to determine the incidence of HEV infection among HIV-1 patients compared to individuals without HIV-1 infection. Methods: In our cross-sectional study, 87 HIV-1-positive patients were compared to 93 healthy individuals in Kerman, Iran. Plasma and peripheral blood mononuclear cells (PBMCs) were obtained from all the participants. Plasma samples were evaluated for HEV IgM and IgG using the ELISA kit. Then, reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) was used in RNA extractions from PBMCs to check for the presence of HEV RNA. Results: Among the subjects examined in our study, 61 (70.1%) and 71 (77.4%) out of patients with HIV-1 infection and healthy individuals were male, respectively. The average ages of patients with HIV-1 and the control group were 40.2 years and 39.9 years, respectively. No discernible differences were found between the two groups based on IgM and IgG seropositivity against the HEV. However, HEV-RNA was found in 8% of patients with HIV-1 and 1.1% of HIV-1-negative individuals (P=0.03). There was also an association between the HEV genome and anti-HEV and anti-HCV antibodies in HIV-1-positive patients (P=0.02 and P=0.014, respectively). Conclusion: HEV infection may be more common in HIV-1 patients and may develop a chronic infection in immunocompromised individuals. Molecular-based HEV diagnostic tests, including RT-PCR assays, should be performed in HIV-1 patients with unknown impaired liver function tests.

Lipid-Based Delivery Systems for Flavonoids and Flavonolignans: Liposomes, Nanoemulsions, and Solid Lipid Nanoparticles.

Herbal chemicals with a long history in medicine have attracted a lot of attention. Flavonolignans and flavonoids are considered as two classes of the above-mentioned compounds with different functional groups which exhibit several therapeutic capabilities such as antimicrobial, anti-inflammatory, antioxidant, antidiabetic, and anticancer activities. Based on the studies, high hydrophobic properties of the aforementioned compounds limit their bioavailability inside the human body and restrict their wide application. Nanoscale formulations such as solid lipid nanoparticles, liposomes, and other types of lipid-based delivery systems have been introduced to overcome the above-mentioned challenges. This approach allows the aforementioned hydrophobic therapeutic compounds to be encapsulated between hydrophobic structures, resulting in improving their bioavailability. The above-mentioned enhanced delivery system improves delivery to the targeted sites and reduces the daily required dosage. Lowering the required daily dose improves the performance of the drug by diminishing its side effects on non-targeted tissues. The present study aims to highlight the recent improvements in implementing lipid-based nanocarriers to deliver flavonolignans and flavonoids.

Tissue factor (coagulation factor III): a potential double-edge molecule to be targeted and re-targeted toward cancer.

Tissue factor (TF) is a protein that plays a critical role in blood clotting, but recent research has also shown its involvement in cancer development and progression. Herein, we provide an overview of the structure of TF and its involvement in signaling pathways that promote cancer cell proliferation and survival, such as the PI3K/AKT and MAPK pathways. TF overexpression is associated with increased tumor aggressiveness and poor prognosis in various cancers. The review also explores TF's role in promoting cancer cell metastasis, angiogenesis, and venous thromboembolism (VTE). Of note, various TF-targeted therapies, including monoclonal antibodies, small molecule inhibitors, and immunotherapies have been developed, and preclinical and clinical studies demonstrating the efficacy of these therapies in various cancer types are now being evaluated. The potential for re-targeting TF toward cancer cells using TF-conjugated nanoparticles, which have shown promising results in preclinical studies is another intriguing approach in the path of cancer treatment. Although there are still many challenges, TF could possibly be a potential molecule to be used for further cancer therapy as some TF-targeted therapies like Seagen and Genmab's tisotumab vedotin have gained FDA approval for treatment of cervical cancer. Overall, based on the overviewed studies, this review article provides an in-depth overview of the crucial role that TF plays in cancer development and progression, and emphasizes the potential of TF-targeted and re-targeted therapies as potential approaches for the treatment of cancer.

Efficacy and Safety of a Persian Medicine Formula on Functional Dyspepsia Symptoms: A Randomized Double-Blind Active-Control Clinical Trial.

INTRODUCTION: Functional dyspepsia (FD) is one of the most frequent gastrointestinal disorders with a high burden. Although FD is a heterogeneous disorder without any standard therapy (treatment/treatment - repetition), there is a wide history of using herbal remedies for its treatment. Two of these herbal remedies quoted in various Persian medicine resources are celery and ajwain. Their effects have been investigated in recent clinical trials in FD patients. We aimed to compare the effect of celery and ajwain to that of domperidone in patients with postprandial distress syndrome. METHODS: This is a randomized double-blind active-control clinical trial, conducted at Kerman, Iran in 2020. Participants of this study were 100 patients suffering from FD (postprandial distress syndrome subtype). The intervention group received 1 g of the combination of celery and ajwain (Apium graveolens L. and Trachyspermum copticum [L.] Link), while the control group received 30 mg of domperidone per day for 4 consecutive weeks. Primary outcomes were symptom severity and frequency, and secondary outcomes were quality of life (QoL) and safety. All outcomes were assessed at the end of the trial and also 4 weeks after the trial was finished. RESULTS: No significant differences in symptom frequency were found between groups. However, differences in symptom severity were found at the end of the follow-up (week 8) (p = 0.001). The intragroup analysis showed a significant decrease in the symptoms severity and frequency at the end of week 4 in both groups (p < 0.001). QoL in the intervention group was higher compared to the control group at the end of the study (p < 0.001) and at the point of the follow-up (week 8; p < 0.001). No serious adverse events occurred in either group. CONCLUSION: The herbal mixture of celery and ajwain could be considered a safe and effective remedy, decreasing the severity of symptoms and increasing QoL in patients with postprandial distress syndrome. It is further suggested to confirm these findings in high-quality multi-center clinical trials.

Dexamethasone as an anti-cancer or hepatotoxic.

The linkage between inflammation and oxidative stress in liver damage has been proven and is undeniable; dexamethasone with some antioxidants can reduce the toxicity of liver tissue. Due to the importance of cancer treatment, glucocorticoids' synergistic effect in inhibiting cancer cell growth is also investigated. Dexamethasone alone and combined with etoposide were tested at concentrations of 1, 5, and 10 µM to evaluate the potency of dexamethasone in inhibiting the growth of A549 cells using oxidative stress factors and DNA damage. Also, intraperitoneal injection of dexamethasone in rats was used to induce liver toxicity. Coenzyme Q10 at different concentrations (1, 10, and 50 mg/kg) was used as an antioxidant to assess the oxidative stress factors and measure Caspase-3 activity. The results showed that dexamethasone combined with etoposide could significantly inhibit the growth of cancer cells and induce apoptosis. Treatment of A549 cells using dexamethasone also inhibits cancer cells' growth by inducing oxidative stress and DNA damage. Dexamethasone also, by inducing oxidative stress and activation of caspase 3, ultimately causes hepatotoxicity. Treatment with different concentrations of CoQ10 showed improved mitochondrial function, antioxidant defense, and liver enzyme. The best effect of coenzyme Q10 on dexamethasone-induced hepatotoxicity is 50 mg/kg. As a result, dexamethasone (alone and combined with etoposide) has an anti-cancer effect by damaging DNA and inducing oxidative stress. Also, CoQ10 has antioxidant effects against dexamethasone-induced hepatotoxicity by improving mitochondrial function and reducing caspase-3 activity.

Opium Use and the Risk of Liver Cancer: A Case-Control Study.

Limited evidence is available to acknowledge the association between opium use and liver cancer. In a case-control study, we recruited 117 cases of primary liver cancer (PLC) and 234 age and sex-matched neighborhood controls from 2016 to 2018. We calculated odds ratios (OR) for opium use and 95% confidence intervals (95% CI), using conditional logistic regressions. Compared with non-users the adjusted OR (AOR, 95% CI) for opium use was 6.5 (95% CI, 2.87-13.44). Compared with people who had no history of use, a strong dose-response effect of opium use was observed by amount of use (AOR, 10.70; 95% CI, 3.92-28.70). Cumulative use of opium also indicated that using over 30 gr-year could increase the PLC risk dramatically (AOR, 11.0; 95% CI, 3.83-31.58). Those who used opium for more than 21 years were highly at risk of PLC (AOR, 11.66; 95% CI, 4.43-30.67). The observed associations were significant even among never tobacco smokers (including cigarette and water-pipe smoking). PREVENTION RELEVANCE: The results of this study indicate that opium use dramatically increased the risk of liver cancer. Because opioids are increasing for medical and non-medical use globally; accordingly, severe health consequences such as liver cancer have to be investigated widely.

Detecting diseases in medical prescriptions using data mining methods.

Every year, the health of millions of people around the world is compromised by misdiagnosis, which sometimes could even lead to death. In addition, it entails huge financial costs for patients, insurance companies, and governments. Furthermore, many physicians' professional life is adversely affected by unintended errors in prescribing medication or misdiagnosing a disease. Our aim in this paper is to use data mining methods to find knowledge in a dataset of medical prescriptions that can be effective in improving the diagnostic process. In this study, using 4 single classification algorithms including decision tree, random forest, simple Bayes, and K-nearest neighbors, the disease and its category were predicted. Then, in order to improve the performance of these algorithms, we used an Ensemble Learning methodology to present our proposed model. In the final step, a number of experiments were performed to compare the performance of different data mining techniques. The final model proposed in this study has an accuracy and kappa score of 62.86% and 0.620 for disease prediction and 74.39% and 0.720 for prediction of the disease category, respectively, which has better performance than other studies in this field.In general, the results of this study can be used to help maintain the health of patients, and prevent the wastage of the financial resources of patients, insurance companies, and governments. In addition, it can aid physicians and help their careers by providing timely information on diagnostic errors. Finally, these results can be used as a basis for future research in this field.

The effect of combining basil seeds and gum Arabic on the healing process of experimental acetic acid-induced ulcerative colitis in rats.

Background & aim: Ulcerative colitis (UC) is a chronic recurrent inflammatory disease of the large intestine and rectum that oxidative stress and severe inflammation are the main features of this disease. Previous studies have shown that separate consumption of basil and gum arabic can reduce inflammation and oxidative stress. The aim of the study was evaluating the effect of treatment with basil seeds given together with gum arabic on healing, inflammation and oxidative stress in the course of experimental colitis in rats. Experimental procedure: A total number of 50 male rats were used, randomly assigned to five groups of 10 rats each. Colitis was induced in rats by enemas with 4% solution od acetic acid. Four days after induction of colitis, rats were treated for next 4 days with saline or combination of basil seeds plus gum arabic (1 mg/kg) or sulfasalazine (100 mg/g) rectally. The experiment was terminated after last dose of treatment. Rats without induction of colitis were used as a sham group. Results: Acetic acid-induced colitis increased the macroscopic and histopathological damage scores of the colon as well as colon levels of MDA(Malondialdehyde), MPO(Myeloperoxidase), TNFα(Tissue necrosis factor α), IL6 (Interleukin 6)and IL17(Interleukin 17) and decreased SOD(Superoxide Dismutase), GPx (Glutathione Peroxidase) and IL10 (Interleukin 10) levels compared with the control group(P < 0.001). Treatment with basil and gum arabic reduced macroscopic and histopathological damage scores (P < 0.01) of the colon, MDA, MPO, TNFα, IL6(P < 0.001) and IL17 (P < 0.01) levels of the colon and increased SOD, GPx and IL10 levels compared to the colitis group (P < 0.01). Conclusion: Rectal administration of combination of basil seeds plus gum arabic after induction of colitis, exhibits antioxidant and anti-inflammatory effects, and accelerates the healing of the colon in experimental colitis evoked by acetic acid.

Amlodipine: Can act as an antioxidant in patients with transfusion-dependent ß-thalassemia? A double-blind, controlled, crossover trial.

BACKGROUND AND AIM: This study aimed to assess the antioxidant effects of amlodipine in transfusion-dependent ß-thalassemia (TDT) patients. METHODS: This crossover trial consisted of two sequences (AP and PA). In the AP sequence, nine cases received amlodipine 5 mg daily (phase I) and then were switched to placebo (phase II). In PA sequence, 10 patients took the placebo (phase I) and were shifted to amlodipine (phase II). The washout period was 2 weeks. The length of each phase was 6 months. Serum malondialdehyde (MDA, µmol/L), carbonyl (protein CO, µM/L), glutathione (GSH, nM/L), and total antioxidant capacity (TAC, µmol FeSO4/L) were measured in the beginning and at the end of phases I and II. The clinical significance was viewed as a minimum change difference of 5% for each outcome between amlodipine and placebo. RESULTS: Seventeen cases completed the study. According to the baseline MDA values, the adjusted Hedges's g for MDA was -0.59, 95% confidence interval [CI] -1.26 to 0.08. After controlling the baseline protein CO values, Hedges's g computed for protein CO was -0.11, 95% CI -0.76 to 0.55. The estimated values of the adjusted Hedges's g for GSH and TAC were also 0.26, 95% CI -0.40 to 0.91, and 0.42, 95% CI -0.24 to 1.09, respectively. The change difference for MDA was 8.3% (protein CO 2.2%, GSH 3.1%, and TAC 12.9%). CONCLUSION: Clinically, amlodipine therapy is an efficacious adjuvant treatment with conventional iron chelators for improving the levels of MDA and TAC in patients with TDT.

Ferritin thresholds for cardiac and liver hemosiderosis in ß-thalassemia patients: a diagnostic accuracy study.

Ferritin is frequently used to screen some dire consequences of iron overload in ß-thalassemia patients. The study aimed to define the best cutoff point of ferritin to screen for cardiac and liver hemosiderosis in these cases. This was a registry-based study on ß-thalassemia patients living throughout Mazandaran province, Iran (n = 1959). In this diagnostic research, the index test was ferritin levels measured by a chemiluminescent immunoassay. As a reference test, T2*-weighted magnetic resonance imaging (T2*-weighted MRI) was applied to determine cardiac and liver hemosiderosis. A cutoff point of 2027 ng/mL for ferritin showed a sensitivity of 50%, specificity 77.4%, PPV 42.1%, and NPV 82.5% for cardiac hemosiderosis (area under curve [AUC] 0.66, 95% CI 0.60-0.71, adjusted odds ratio [OR] 2.05, 95% CI 1.05-4.01). At an optimum cutoff point of 1090 ng/mL, sensitivity 66.7%, specificity 68%, PPV 82.9%, and NPV 46.8% for liver hemosiderosis were estimated (AUC 0.68, 95% CI 0.63-0.73, adjusted OR 3.93, 95% CI 2.02-7.64. The likelihood of cardiac hemosiderosis serum ferritin levels below 2027 ng/mL is 17.5%. Moreover, 82.9% of ß-thalassemia patients with serum ferritin levels above 1090 ng/mL may suffer from liver hemosiderosis, regardless of the grades.

Tuning the polymer thermal conductivity through structural modification induced by MoS2 bilayers.

The present work refers to a physical and structural study of nanoconfined polymers in polymer-MoS2 nanocomposites as a function of MoS2-MoS2 interlayer distance. We applied reverse nonequilibrium molecular dynamics (RNEMD) simulations to investigate the thermal conductivity (λ) of polyamide oligomers confined by MoS2 bilayers. The results of this study indicate that thermal conductivity of polymer can be considerably enhanced when polymer chains are confined by MoS2 sheets, this behavior is more pronounced by charged surfaces. The presence of MoS2 surfaces leads to elongation as well as preferential alignment of polymer chains parallel to the MoS2 surfaces, which in turn results in higher order and denser packing of polymer content and hence larger thermal conductivity in comparison to the bulk polymer. Additionally, the analysis of the number of hydrogen bonds (HBs) in confined polymer chains suggests that a combined effect of the mentioned structural modification and enlarged values of HBs may cooperatively contribute to high polymer thermal conductivity, facilitating phonon transport. The results reported here suggest a significant way to design confined polymer-MoS2 composites for significantly improving thermal conductivity for a wide variety of applications.

Mortality Trends of Gastrointestinal, Liver, and Pancreaticobiliary Diseases: A Hospital-Based Prospective Study in the Southeast of Iran.

Background: Gastrointestinal (GI), liver, and pancreaticobiliary diseases, in addition to the high health care utilization, account for a significant proportion of disability and death in Iran. We aimed to assess the incidence of in-hospital mortality for the total GI, liver, and pancreaticobiliary diseases in all hospitals in Kerman, Iran. Methods: In a cross-sectional study from May 2017 to April 2018, we collected the data of in-hospital death records due to GI, liver, and pancreaticobiliary diseases in all hospitals in Kerman city. GI and liver diseases were classified into three main categories: 1. Non-malignant GI diseases, 2. Non-malignant liver and pancreaticobiliary diseases, and 3. GI, liver, and pancreaticobiliary malignancies. All data were analyzed using SPSS software, version 22 (IBM). Results: Of 3427 in-hospital mortality, 269 (7.84%) deaths were due to GI, liver, and pancreaticobiliary diseases, of which 82 (30.48%) were related to non-malignant GI disorders, 92 (34.20%) to the non-malignant liver and pancreaticobiliary diseases, and 95 (35.31%) were associated with GI, liver and pancreaticobiliary malignancies. Most patients were male (62.08%), and the most common age was between 60-80 years (40.5%). GI bleeding occurred in 158 (58.73%) patients, and variceal bleeding was the most common cause (28.48%). Additionally, cirrhosis was reported in 41 out of 92 (44.56%), and hepatitis B virus (HBV) was the most common cause of cirrhosis among 17 out of 41 (41.46%). Conclusion: Our results show that gastric, colorectal, and pancreatic cancers and cirrhosis due to HBV were the most common causes of mortality associated with GI, liver, and pancreaticobiliary diseases in the hospitals of Kerman.

Opium use as an independent risk factor for pancreatic cancer: A case-control study.

BACKGROUND: Pancreatic cancer (PC) is ranked as the seventh leading cause of cancer deaths worldwide. The current study was conducted to explore the correlation between the use of opium and its derivatives (opium) and PC in Iran. METHODS: In this case-control study which was conducted in Kerman province, south east part of Iran; 176 patients with PC, and 352 healthy individuals as the control group were matched in terms of age, sex, and place of residence. A structured questionnaire including questions of opium usage, alcohol usage, cigarette smoking, and diet was used to collect the data. The relation between the use of opium and PC was adjusted for tobacco smoking, education, daily intake of fruit, vegetables, red meat, and hydrogenated fats and analyzed using the conditional logistic regression. RESULTS: There was a positive relationship between the opium use and the increased risk of PC (Adjusted Odds Ratio (AOR) = 4.33, 95 % CI: 2.09-8.95), which was even stronger than its association with cigarette smoking (AOR = 1.67, 95 % CI: 0.86-3.24), although their difference was not statistically significant. A significant dose-response relation was detected between the use of opium; as the relation was stronger in heavy users (AOR low users = 4.93, 95 % CI: 1.79-13.54 and AOR heavy users = 5.10, 95 % CI: 2.10-12.35). Moreover, PC was higher among participants starting the use of opium at a younger age than those who started opium at an older age (AOR = 8.03, 95 % CI: 3.19-20.23). CONCLUSION: This study demonstrated that opium use is associated with a high and strong risk of PC as an independent risk factor. Further studies should be done to reduce the use of opium in Iran and other world countries.

Coadministration of silymarin with iron chelators in transfusion-dependent ß-thalassemia patients: a systematic review and meta-analysis for effect on iron overload.

Background and aim: We conducted a systematic review to apprise the efficacy of silymarin in conjunction with standard iron chelators on iron overload for transfusion-dependent ß-thalassemia (TDT) patients.Methods: We searched PubMed, Web of Science, Scopus, Sciencedirect, the Cochrane Library (the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials (CENTRAL) to 1 May 2020. All randomized controlled trials (RCTs) studies comparing the effect of iron chelators alone versus silymarin plus standard routine treatment on iron burden amid TDT were included in this review. Primary outcomes comprised serum ferritin level (ng/mL), liver iron concentration (LIC Fe/kg dry weight), and total iron binding capacity (TIBC mcg/dL)Results: Combination therapy of silymarin and iron chelators showed a significant improvement in serum ferritin level in TDT patients, compared to nonsilymarin users [eight studies, n = 477]; weighted mean difference (WMD) -1.79, 95% confidence interval [CI] -2.86 to -0.72, I2 96.1%; P = 0.001. Concurrent treatment with silymarin failed to significantly decrease LIC in TDT patients [two studies, n = 106]; WMD 0.74, 95% CI -1.62 to 3.10, I2 96.6%; P = 0.54.Conclusion: There is no evidence of the effectiveness of adding silymarin to standard iron chelators to reduce iron load in TDT.

The Interrelationship between Liver Function Test and the Coronavirus Disease 2019: A Systematic Review and Meta-Analysis.

Background: The outbreak of the coronavirus disease-2019 (COVID-19) has become a global public health challenge. Assessing the effect of COVID-19 on liver injury is of great importance. A systematic review and meta-analysis were conducted to establish the characteristics of liver function tests in COVID-19 patients. Methods: A systematic search of publications from December 2019 up to April 2020 in Web of Science, Scopus, and Medline (via PubMed) databases was performed. Both cross-sectional and case series studies reporting an association between liver injury and COVID-19 infection were included. The data were analyzed using the STATA software (version 11.0) and the random-effects model for I2>50% was used to pool the results. Results: In this meta-analysis, 42 articles comprising a total of 6,557 COVID-19 patients were studied. The prevalence of increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was 30% and 21% in non-severe patients and 38% and 48% in severe patients, respectively. Patients with severe COVID-19 infection were 4.22, 4.96, and 4.13 times more likely to have elevated AST, ALT, and lactate dehydrogenase (LDH) levels, respectively. Conclusion: Elevation in liver function tests was higher in patients with severe than non-severe COVID-19 infection. Given the widespread use of drugs that increases the risk of hepatotoxicity, healthcare providers should be aware of changes in liver enzymes in COVID-19 patients. The inclusion of other studies from outside China could confirm the pattern of elevation in liver function tests in COVID-19 patients across the globe. Preprint of this article is available on medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.20.20108357v1.

Persian Herbal Medicine in Functional Dyspepsia: A Systematic Review.

INTRODUCTION: According to Rome IV, functional dyspepsia is diagnosed with the presence of dyspepsia in the absence of organic or metabolic causes. FD caused by several factors, such as impaired gastric accommodation and hypersensitivity to gastric distention. Several studies have reported the effectiveness of herbal medicine on FD. This article, thus, reviews Persian herbal medicine in FD. METHODS: Electronic databases, including Pubmed, Scopus, Cochrane, Embase, Web of science and Ovid, were searched so as to find clinical articles related to dyspepsia and herbal medicine by July 2019. Our search strategies were traditional medicine, complementary and alternative medicine, herb, plant, and dyspepsia. We excluded all articles except Persian clinical trials. RESULTS: We found 34 clinical trials with 15 herbs and 4 compound herbal remedies like Asparagus racemosus, Brassica oleracea, Cynara scolymus, Ocimum basilicum, Mentha longifolia, Mentha pulegium, Mentha piperata, Pimpinella anisum, Nigella sativa, Mastic gum, Curcuma longa, Pistatio Atlantica, Glycyrrhiza glabra, Solanum tuberosum and Zingiber officinale and compound remedies of Rosa damascene & Crocus sativus, Trachyspermum copticom & Apium graveolence, Carum carvi & Mentha pipperata, Gingiber officinalis & Cynara scolymus are effective in functional dyspepsia. CONCLUSION: Many people use herbal and traditional remedies for the treatment of disorders such as gastrointestinal disorders, especially in Asian countries. Several studies reported the efficacy of herbal medicine in functional dyspepsia. Although their mechanisms are not fully understood, it seems they can modulate GI motility and improve symptoms of FD.

Moderate to severe liver siderosis and raised AST are independent risk factors for vitamin D insufficiency in ß-thalassemia patients.

Numerous problematic disorders such as vitamin D (Vit-D) deficiency subsequent to large iron loading can be developed in patients with ß-thalassemia. The study aimed to estimate Vit-D insufficiency and its risk factors in patients with ß-thalassemia. In this multicenter and observational study, all ß-thalassemia patients, who referred to 14 hospital-based thalassemia divisions or clinics in Mazandaran province, Iran were included in the study. The data belong to December 2015 until December 2019. The study population was made of transfusion dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) patients. Serum levels of 25-OHD3 have been measured by high performance liquid chromatography (HPLC) method as ng/mL. Demographic and clinical information along with some biological tests, as well as the results of T2*-weighted magnetic resonance imaging were analyzed. Of 1959 registered patients, 487 (24.9%) patients had Vit-D-related data. The prevalence of Vit-D insufficiency (< 30 ng/mL) was 41.9, 95% CI 37.5-46.3. The adjusted risks of moderate to severe liver siderosis and raised AST (aspartate aminotransferase) for Vit-D insufficiency (< 30 ng/mL) were 2.31, 95% CI 1.38-3.89 and 2.62, 95% CI 1.43-4.79, respectively. The receiver operating characteristic (ROC) curve analysis showed that the predictive accuracy of ferritin for Vit-D insufficiency status was 0.61, 95% CI 0.54-0.68 with a cutoff point of 1,078 ng/mL (P = 0.03, sensitivity 67%, specificity 49%, positive predictive value [PPV] 47% and negative predictive value [NPV] 68%). In spite of the national programs for treating Vit-D deficiency and our previous efforts for giving supplements to all patients, Vit-D insufficiency/deficiency is still common in our patients. Also, moderate to severe liver siderosis and raised AST were the independent risk factors for the Vit-D insufficiency.