Sleep disorders in patients with endometriosis; a cross-sectional study.

BACKGROUND: Endometriosis affects 10-15% of women of reproductive age and is considered a critical gynecological problem. Endometriosis causes pain and infertility, both of which can impair the patient's quality of life. Sleep disorders account for the most bothersome presentation of impaired quality of life. This study investigated the frequency and severity of sleep disorders in women with endometriosis. METHODS: In this analytical cross-sectional study, 665 women referred to three hospitals in Tehran, Rasool-e-Akram, Pars, and Nikan, were included (463 patients with endometriosis and 202 women without endometriosis). All of them were informed about the study design and the aim of the research, and then they were asked to sign the consent form and complete the Pittsburgh Sleep Quality Index (PSQI). After data gathering and entering, they were analyzed by SPSS version 22 and were considered significant with P < 0.05. RESULTS: The study population's mean age was 35.4 ± 7.9 years. The mean global PSQI score in the case group (endometriosis patients) was higher than in the control group (non-endometriosis patients) (10.6 vs. 7.1; P < 0.001). Patients with dyspareunia, dysuria, pelvic pain, and dyschezia had a significantly higher PSQI score (P < 0.05). CONCLUSION: According to the findings of the present study, the sleep quality in endometriosis patients is low, and there is a need to pay greater attention to these patients. This may result in some changes in the therapeutic strategies for this disease.

Hesperidin suppressed metastasis, angiogenesis and tumour growth in Balb/c mice model of breast cancer.

Considering the unfavourable response of breast cancer (BC) to treatment, we assessed the therapeutic potential hesperidin in mice bearing 4T1 BC tumours. Anti-tumour effects were assessed by measuring pathologic complete response (pCR), survival analysis, immunohistochemistry for E-cadherin, VEGF, MMP9, MMP2 and Ki-67, serum measurement of IFNγ and IL-4, and gene expression analysis of CD105, VEGFa, VEGFR2 and COX2. Survival of tumour-bearing mice was the highest in mice receiving a combination of hesperidin and doxorubicin (Dox) (80%) compared to the normal saline (43%), hesperidin 5 (54%), 10 (55.5%), 10 (60.5%) and 40 (66%) mg/kg, and 10 mg/kg Dox-treated (73%) groups (p < 0.0001 for all). Compared to the normal saline group, there was a significant elevation in IFNγ level in the animals receiving 20 (p = 0.0026) and 40 (p < 0.001) mg/kg hesperidin, 10 mg/kg Dox (p < 0.001), and combined hesperidin (20 mg/kg) and Dox (10 mg/kg) (p < 0.001). A significant reduction in the gene expression of CD 105 (p = 0.0106), VEGFa (p < 0.0001), VEGFR2 (p < 0.0001), and Cox2 (p = 0.034) and a significant higher pCR score (p = 0.006) were noticed in mice treated with 10 mg/kg Dox + 20 mg/kg hesperidin compared to those treated with 10 mg/kg Dox alone. Immunohistochemical staining showed significant reductions in Ki-67 (p < 0.001) and VEGF (p < 0.001) and a significant elevation in E-cadherin (p = 0.005) in the 10 mg/kg Dox + 20 mg/kg treatment group than in 10 mg/kg Dox alone group. Hesperidin can be considered as a potentially suitable anti-cancer agent for BC that can synergize with other chemotherapeutics.

Is it possible to reduce the rate of vertical transmission and improve perinatal outcomes by inclusion of remdesivir in treatment regimen of pregnant women with COVID-19?

BACKGROUND: Coronavirus disease 2019 (COVID-19) is currently one of the world's most critical health issues so far. Given the importance of appropriate treatment in pregnancy and the controversies about Remdesivir effectiveness and complications, the present study aimed to evaluate the impact of Remdesivir on maternal, fetal, and perinatal outcomes in pregnant women with COVID-19 diseases. METHODS: A total of 189 pregnant women with positive polymerase chain reaction (PCR) results for SARS-COV-2, and oxygen saturation [SpO2] of < 95%) were admitted to 12 hospitals affiliated with the Iran University of Medical Sciences from March 1st, 2020 to June 7th, 2021, namely the first four COVID-19 Picks in Iran. They were enrolled in this retrospective cohort study by census method and categorized into case and control groups, based on the inclusion of Remdesivir in their treatment protocol. Demographics, clinical outcomes, and pregnancy-related complications of the mothers and the neonates were compared between the two study groups. RESULTS: A comparison of 54 mothers in the case and 135 in the control group showed no demographic and clinical characteristics difference. Neonates whose mothers did not receive Remdesivir had a higher rate of positive PCR (10.2%), compared to the Remdesivir group (1.9%) with a relative risk of 0.91 reported for Remdesivir (95% CI: 0.85-0.98, P = 0.04); besides, Remdesivir resulted in fewer neonatal intensive care unit admission rates in mild/moderate COVID-19 group (RR = 0.32, 95% CI: 0.105-1.02, P = 0.03). Although neonatal death between the two groups was not statistically significant, from the clinical point seems important; 1(1.9%) in the case vs. 9(7.2%) in the control group. Interestingly LOS (Length of Stay) in the hospital was longer in the case group (median of 7 vs. 3 days; P < 0.0001). CONCLUSION: The inclusion of Remdesivir in the treatment protocol of pregnant women with COVID-19 may reduce vertical transmission and improve perinatal outcomes, thus being suggested to be considered.

Promising Anti-atherosclerotic Effect of Berberine: Evidence from In Vitro, In Vivo, and Clinical Studies.

Elevated levels of plasma cholesterol, impaired vascular wall, and presence of inflammatory macrophages are important atherogenic risk factors contributing to atherosclerotic plaque formation and progression. The interventions modulating these risk factors have been found to protect against atherosclerosis development and to decrease atherosclerosis-related cardiovascular disorders. Nutritional approaches involving supplements followed by improving dietary habits and lifestyle have become growingly attractive and acceptable methods used to control atherosclerosis risk factors, mainly high levels of plasma cholesterol. There are a large number of studies that show berberine, a plant bioactive compound, could ameliorate atherosclerosis-related risk factors. In the present literature review, we put together this studies and provide integrated evidence that exhibits berberine has the potential atheroprotective effect through reducing increased levels of plasma cholesterol, particularly low-density lipoprotein (LDL) cholesterol (LDL-C) via LDL receptor (LDLR)-dependent and LDL receptor-independent mechanisms, inhibiting migration and inflammatory activity of macrophages, improving the functionality of endothelial cells via anti-oxidant activities, and suppressing proliferation of vascular smooth muscle cells. In conclusion, berberine can exert inhibitory effects on the atherosclerotic plaque development mainly through LDL-lowering activity and suppressing atherogenic functions of mentioned cells. As the second achievement of this review, among the signaling pathways through which berberine regulates intracellular processes, AMP-activated protein kinase (AMPK) has a central and critical role, showing that enhancing activity of AMPK pathway can be considered as a promising therapeutic approach for atherosclerosis treatment.

Melatonin and cancer suppression: insights into its effects on DNA methylation.

Melatonin is an important naturally occurring hormone in mammals. Melatonin-mediated biological effects include the regulation of circadian rhythms, which is important for optimal human health. Also, melatonin has a broad range of immunoenhancing actions. Moreover, its oncostatic properties, especially regarding breast cancer, involve a variety cancer-inhibitory processes and are well documented. Due to their promising effects on the prognosis of cancer patients, anti-cancer drugs with epigenetic actions have attracted a significant amount of attention in recent years. Epigenetic modifications of cancers are categorized into three major processes including non-coding RNAs, histone modification, and DNA methylation. Hence, the modification of the latter epigenetic event is currently considered an effective strategy for treatment of cancer patients. Thereby, this report summarizes the available evidence that investigated melatonin-induced effects in altering the status of DNA methylation in different cancer cells and models, e.g., malignant glioma and breast carcinoma. Also, we discuss the role of artificial light at night (ALAN)-mediated inhibitory effects on melatonin secretion and subsequent impact on global DNA methylation of cancer cells.

Curcumin in Advancing Treatment for Gynecological Cancers with Developed Drug- and Radiotherapy-Associated Resistance.

The development of resistance toward current cancer therapy modalities is an ongoing challenge in gynecological cancers, especially ovarian and cervical malignancies that require further investigations in the context of drug- and irradiation-induced resistance. In this regard, curcumin has demonstrated beneficial and highly pleiotropic actions and increased the therapeutic efficiency of radiochemotherapy. The antiproliferative, anti-metastatic, anti-angiogenic, and anti-inflammatory effects of curcumin have been extensively reported in the literature, and it could also act as a chemopreventive agent which mitigates the out-of-target harmful impact of chemotherapeutics on surrounding normal tissues. The current review discussed the modulating influences of curcumin on some cell and molecular features, including the cell signaling and molecular pathways altered upon curcumin treatment, the expression of target genes involved in the progression of gynecological cancers, as well as the expression of genes accountable for the development of resistance toward common chemotherapeutics and radiotherapy. The cell molecular targets implicated in curcumin's resensitizing effect, when used together with cisplatin, paclitaxel, and irradiation in gynecological cancers, are also addressed. Finally, rational approaches for improving the therapeutic benefits of curcumin, including curcumin derivatives with enhanced therapeutic efficacy, using nanoformulations to advance curcumin stability in physiological media and improve bioavailability have been elucidated.

Correction to: Curcumin in Advancing Treatment for Gynecological Cancers with Developed Drug- and Radiotherapy-Associated Resistance.

The affiliation of the 6th author Dr. Abolfazl Mehdizadehkashi was incorrect. It has been corrected to Endometriosis Research Center, Iran University of Medical Sciences, Tehran, Iran.

Anti-inflammatory and immune-modulatory impacts of berberine on activation of autoreactive T cells in autoimmune inflammation.

Autoreactive inflammatory CD4+ T cells, such as T helper (Th)1 and Th17 subtypes, have been found to associate with the pathogenesis of autoimmune disorders. On the other hand, CD4+ Foxp3+ T regulatory (Treg) cells are crucial for the immune tolerance and have a critical role in the suppression of the excessive immune and inflammatory response promoted by these Th cells. In contrast, dendritic cells (DCs) and macrophages are immune cells that through their inflammatory functions promote autoreactive T-cell responses in autoimmune conditions. In recent years, there has been increasing attention to exploring effective immunomodulatory or anti-inflammatory agents from the herbal collection of traditional medicine. Berberine, an isoquinoline alkaloid, is one of the main active ingredients extracted from medicinal herbs and has been shown to exert various biological and pharmacological effects that are suggested to be mainly attributed to its anti-inflammatory and immunomodulatory properties. Several lines of experimental study have recently investigated the therapeutic potential of berberine for treating autoimmune conditions in animal models of human autoimmune diseases. Here, we aimed to seek mechanisms underlying immunomodulatory and anti-inflammatory effects of berberine on autoreactive inflammatory responses in autoimmune conditions. Reported data reveal that berberine can directly suppress functions and differentiation of pro-inflammatory Th1 and Th17 cells, and indirectly decrease Th cell-mediated inflammation through modulating or suppressing other cells assisting autoreactive inflammation, such as Tregs, DCs and macrophages.

The potential therapeutic effects of curcumin on pregnancy complications: Novel insights into reproductive medicine.

Pregnancy complications including preeclampsia, preterm birth, intrauterine growth restriction, and gestational diabetes are the main adverse reproductive outcomes. Excessive inflammation and oxidative stress play crucial roles in the pathogenesis of pregnancy disorders. Curcumin, the main polyphenolic compound derived from Curcuma longa, is mainly known by its anti-inflammatory and antioxidant properties. There are in vitro and in vivo reports revealing the preventive and ameliorating effects of curcumin against pregnancy complications. Here, we aimed to seek mechanisms underlying the modulatory effects of curcumin on dysregulated inflammatory and oxidative responses in various pregnancy complications.

Curcumin as a potential modulator of M1 and M2 macrophages: new insights in atherosclerosis therapy.

Accumulation of macrophages within the artery wall is an eminent feature of atherosclerotic plaques. Macrophages are influenced by various plaque microenvironmental stimuli, such as oxidized lipids, cytokines, and senescent erythrocytes, and thereby polarize into two main phenotypes called proinflammatory M1 and anti-inflammatory M2 macrophages. In the hemorrhagic zones of atheroma, upon exposure to iron, sequestration of iron by M1 macrophages results in an uncontrolled proinflammatory phenotype impairing wound healing, while M2 macrophages phagocytose both apoptotic cells and senescent erythrocytes. M1 macrophages are prominent phenotype in the unstable plaques, in which plaque shoulder contains macrophages mainly present markers of M1 phenotype, whereas the fibrous cap encompassing the necrotic lipid core content macrophages expressed markers of both M1 and M2 subtypes. The abovementioned findings suggest macrophage modulation as a potent approach for atherosclerosis therapy. Curcumin is a polyphenol dietary derived from turmeric with numerous pharmacological activities. Recent in vitro and in vivo studies have indicated that curcumin exerted lipid-lowering effects, and also can modulate function of different macrophage subsets in various macrophage-involved diseases. The current review aimed to present role of macrophage subtypes in atherosclerosis development and progression, and to understand effect of curcumin on macrophage polarization and foam cell formation in the atherosclerosis lesions. Overall, we would address important targets for macrophage modulation in atherosclerotic plaques.

The Role of Quercetin for the Treatment of Endometriosis and Endometrial Cancer: A Comprehensive Review.

Endometrial glands and stroma can be seen outside the uterine cavity in endometriosis, a gynecological disorder linked to estrogen dependency. Hormonal therapies, surgical excision, and non-steroidal anti-inflammatory drug therapy are among the traditional endometriosis treatments, however, various side effects limit their efficacy. Therefore, it is vital to research complementary and alternative therapeutic modalities to decrease the side effects of conventional therapies. While the search for the best endometriosis treatment continues, the focus is being paid to the assistance provided by polyphenols, notably quercetin. A broad spectrum of health-improving benefits of quercetin includes interactions with endometriosis-related molecular targets such as cell proliferation, apoptosis, invasiveness, inflammation, and oxidative stress. According to already-known research, medicines that mimic the physiological effects of quercetin are good candidates for creating novel endometriosis therapies. This review aims to comprehensively review quercetin's potential as a non-pharmacological treatment for endometriosis by interacting with several cellular and molecular targets.

The Role of Genistein and its Derivatives in Ovarian Cancer: New Perspectives for Molecular Mechanisms and Clinical Applications.

Genistein (GEN) is a member of the polyphenol family, known chiefly for its effects on metabolic diseases and gynecological disorders. GEN has anti-cancer properties by inhibiting tumor proliferation, tumor metastasis, invasion, migration, and inducing apoptosis. Ovarian cancer (OC) is ranked 7th among the most common gynecological cancers. Despite its low incidence compared to other cancers, it is the first cause of death among gynecologic malignancies. Surgery and chemotherapy are the main options for treating this fatal cancer. Therefore, further investigations into GEN may aid in the discovery of novel therapeutics for preventing and/or treating OC. In this review, we aim to investigate the role of GEN in ovarian cancer. We investigate the anti-tumor effects of GEN on OC cell lines, including inducing apoptosis, suppressing tumor growth, and inhibiting metastasis. Also, we review the studies investigating GEN's roles as an adjuvant in therapeutic regimens with other chemotherapeutic agents (e.g., cisplatin, quercetin, and gemcitabine).

Modulation of microRNAs expression and cellular signaling pathways through curcumin as a potential therapeutical approach against ovarian cancer: A review.

Short non-coding RNAs called microRNAs (miRNAs) control gene expression by either inhibiting translation or degrading messenger RNA. MiRNAs are crucial for many biological functions, and the deregulation of their expression is strongly linked to the emergence of cancer. A single miRNA controls several gene expressions, allowing it to simultaneously control a number of cellular signaling pathways. As a result, miRNAs may be used as therapeutic targets as well as biomarkers for the prognosis and diagnosis of different cancers. Recent research has shown that natural compounds like curcumin, resveratrol and quercetin exert their pro-apoptotic and/or anti-proliferative impacts by modulating one and/or more miRNAs, which inhibits the growth of cancer cells, induces apoptosis, or increases the effectiveness of conventional cancer therapies. Here, we summarize the most recent developments in curcumin's control over the expression of miRNAs and emphasize the significance of these herbal remedies as a viable strategy in the treatment and prevention of cancer.

LncRNAs and MiRNAs: New Targets for Resveratrol in Ovarian Cancer Research.

Ovarian cancer (OC) is the 3rd common gynecologic cancer. Numerous procedures are involved in the growth of OC, like migration, angiogenesis, proliferation, apoptosis, invasion, and metastasis. Therefore, a better knowledge of the molecular processes complicated in ovarian tumorigenesis can lead to better measures for the prevention and treatment of the disease and its diagnosis. Long non-coding RNAs (LncRNAs), a subclass of non-coding RNAs, are much more diverse than previously thought. It is suggested that these RNAs may play a role in controlling complex cellular signaling mechanisms via binding to proteins and influencing their function. Nevertheless, our acquaintance with the participation of LncRNAs in the pathogenesis of OC is still restricted. Especially, we do not yet recognize how to pharmacologically correct the epi-mutations. Resveratrol, a natural polyphenol mostly derived from grapes, has been evaluated in many studies to find its cancer therapeutic potential. In the current paper, we aimed to review the role of resveratrol as a potential natural product on lncRNAs as novel diagnostic and therapeutic targets in OC and represent new insights for further investigations.

Selective Cellular Uptake and Cytotoxicity of Curcumin-encapsulated SPC and HSPC Liposome Nanoparticles on Human Bladder Cancer Cells.

BACKGROUND: Curcumin is a main bioactive constituent of turmeric (Curcuma longa L.) with pleiotropic health beneficial effects. However, poor bioavailability is the major barrier to the efficient pharmacological effects of curcumin in humans. AIMS: The present study aimed to develop liposome formulations based on soybean phosphatidylcholine (SPC) and hydrogenated SPC (HSPC) to enhance the bioavailability of curcumin in bladder cancer cells. METHODS: Curcumin was encapsulated in HSPC and SPC liposome nanoparticles using the solvent evaporation method. Physical properties, encapsulation efficiency (%), stability, and in vitro drug release of the prepared liposome formulations have been evaluated. The cellular uptake and cytotoxicity of curcumin-encapsulated nanoliposomes on bladder carcinoma HTB9 cell line and normal fibroblast L929 cell line were studied. DNA fragmentation, apoptosis, and genotoxicity assessments have been carried out to determine the molecular mechanisms underlying the cytotoxic effects of liposomal curcumin formulations on bladder cancer cells. RESULTS: The results indicated that curcumin could be efficiently encapsulated in the HSPC and SPC liposome formulations. The liposomal curcumin formulations have shown shelf-life stability for 14 weeks at 4°C. The accelerated stability testing showed that curcumin encapsulated in nanoliposomes was significantly (p < 0.001) more stable than free curcumin at various pH degrees ranging from alkaline to acidic pH. The in vitro drug release study showed curcumin to be sustainably released from the liposome nanoparticles. Of note, SPC and HSPC nanoliposome formulations significantly increased the cellular uptake and cytotoxicity of curcumin on bladder cancer HTB9 cells. Mechanistically, liposomal curcumin was found to exert a selective inhibitory effect on the viability of cancer cells by inducing apoptosis and DNA damage. CONCLUSION: In conclusion, SPC and HSPC liposome nanoparticles can significantly increase the stability and bioavailability of curcumin, which are important for improving its pharmacological effect.

Dysregulation of miRNA expression in patients with chronic myelogenous leukemia at diagnosis: a systematic review.

Aim: The present systematic review aimed to explore miRNAs as a potential biomarker for early diagnosis of chronic myeloid leukemia (CML). Materials & methods: A systematic search was conducted in three electronic databases, including Web of Science, Scopus and PubMed, to obtain relevant articles investigating the alteration of miRNA expression in patients with CML. Results: The authors found miRNAs whose expression changes are effective in the induction of CML disease. Among them, miR-21 and miR-155 were identified as the most common miRNAs with increased expression and miR-150 and miR-146 as the most common miRNAs with decreased expression. Conclusion: miRNAs can be used as an indicator for the early detection and treatment of CML phase.

Potential therapeutic effects of Ivermectin in COVID-19.

COVID-19 is a critical pandemic that affected communities around the world, and there is currently no specific drug treatment for it. The virus enters the human cells via spikes and induces cytokine production and finally arrests the cell cycle. Ivermectin shows therapeutic potential for treating COVID-19 infection based on in vitro studies. Docking studies have shown a strong affinity between Ivermectin and some virulence factors of COVID-19. Notably, clinical evidence has demonstrated that Ivermectin with usual doses is effective by both the prophylactic and therapeutic approaches in all phases of the disease. Ivermectin inhibits both the adhesion and replication of the virus. Local therapy of the lung with Ivermectin or combination therapy may get better results and decrease the dose of the drug.

Chitosan: A compound for drug delivery system in gastric cancer-a review.

Gastric cancer is known as the fourth most common cancer and the second main cause of cancer-related deaths. Gastric cancer has some characteristics including high incidence rates of metastasis and mortality as well as low rates of early diagnosis, radical resection and 5-year survival. Radical surgery and following chemotherapy has been done for patients with early gastric cancer leading to 90 % survival rate in 5-year after operation. Besides, in advanced stage some cases don't have the chance of surgery as well as the risk of metastasis is high in these patients overally leading to poor prognosis. In recent years, finding a suitable drug delivery system for chemotherapeutic drugs in gastric cancer is an considerable subject for researchers. Chitosan is known as an appropriate compound for chemo-drug delivery in cancer treatment due to its high biodegradability and biocompatibility. Moreover, trans-mucosal drug delivery is facilitated by chitosan via its mucoadhesive and cationic features enhancing interaction with mucous membrane. In addition, a large amount of experimental evidence has reported the efficacy of chitosan for drug delivery in gastric cancer. Thus, the aim of this article was to review this evidence as well as new chitosan-based drug delivery systems investigated in gastric cancer.

Potential cytotoxic and anti-metastatic effects of berberine on gynaecological cancers with drug-associated resistance.

Gynaecological disorders, such as cervical, ovarian, and endometrial cancers are the second most prevalent cancer types in women worldwide. Therapeutic approaches for gynaecological cancers involve chemotherapy, radiation, and surgery. However, lifespan is not improved, and novel medications are required. Among various phytochemicals, berberine, a well-known natural product, has been shown to be a promising cancer chemopreventive agent. Pharmacokinetics, safety, and efficacy of berberine have been investigated in the several experiments against numerous diseases. Here, we aimed to provide a literature review from available published investigations showing the anticancer effects of berberine and its various synthetic analogues against gynaecological disorders, including cervical, ovarian, and endometrial cancers. In conclusion, berberine has been found to efficiently inhibit viability, proliferation, and migration of cancer cells, mainly, via induction of apoptosis by both mitochondrial dependent and -independent pathways. Additionally, structural modification of berberine showed that berberine analogues can improve its antitumor effects against gynaecological cancers.

Sleep Quality and its Main Determinants Among Staff in a Persian Private Hospital.

BACKGROUND: Having good quality of sleep is essential to good health. Sleep disorders could incur intangible expenses. The aim of this cross-sectional study was to evaluate the Persian version of the Pittsburgh Sleep Quality Index (PSQI-P) questionnaire administered to 3 categories of workers (clinical personnel, clerical staff, and logistics workers) in a private hospital located in Tehran, Iran. METHODS: In 2017, all Pars hospital personnel were invited to participate in the study. The PSQI-P questionnaire was distributed among Pars hospital staff, who consented to take part in the study. RESULTS: The total personnel in this private hospital was 1151 and 552 of them submitted their answers. According to the statistical analysis performed using SPSS version 19, there was no correlation between sleep quality and gender, marital status, age, job, shift work, or university degree (P value: 0.94, 0.42, 0.59, 0.67, 0.12, 0.23, respectively). However, participants with a lower body mass index (BMI) experienced better overnight sleep quality than overweight and obese participants (P value: 0.025 and 0.032, respectively). In addition, the prevalence of poor sleep quality was higher in those living in the suburbs compared to urban residents (P value: 0.02). CONCLUSION: The study obtained a significant difference in sleep quality based on the participants' BMI and place of residence. Despite the fact that the P value of the job was not significant, it appeared that sleep disorders are common among clinical personnel. Quality of life may be improved by modification of the factors responsible for poor sleep quality.