Diabetes and ovarian cancer: risk factors, molecular mechanisms and impact on prognosis.

BACKGROUND AND AIM: Diabetes mellitus has been linked to a lower rate of cancer survival and an increase in the incidence of most malignancies. Investigations showed that diabetes might affect ovarian cancer (OC) prognosis and survival. Based on the current information, this study intends to review the risk factors, molecular pathways, and impact of diabetes on OC. METHODS: The data was derived from online databases, including Web of Science, PubMed, and Scopus. The inclusion criteria were original studies, which included the risk factors, molecular mechanisms, and impact of diabetes on OC. The effect of different antidiabetic drugs was also discussed in this manuscript. All of the clinical, in vivo, and in vitro studies were included in the present study. RESULTS: The diagnosis of diabetes mellitus negatively affects the survival and prognosis in OC cases. The epidemiologic data shows that the risk of OC increases in patients with diabetes mellitus compared to the healthy population. Insulin-like growth factors family was raised in diabetic patients, which target several mechanisms, including targeting oxidative stress, angiogenesis, and tumor markers. Antidiabetic drugs such as metformin, sitagliptin, and rosiglitazone have a promising effect on elongation of survival and enhancement of prognosis in OC patients. CONCLUSIONS: Diabetes mellitus is a significant risk factor for OC in women, and it negatively impacts survival and prognosis. Molecular mechanisms such as IGF family, oxidative stress, and inflammatory cytokines have been identified to explain this relationship. Antidiabetic drugs like metformin, sitagliptin, and rosiglitazone have shown promise in improving survival and prognosis of OC patients.

Comprehensive health risk analysis of heavy metal pollution using water quality indices and Monte Carlo simulation in R software.

Rapid urbanization, population growth, agricultural practices, and industrial activities have led to widespread groundwater contamination. This study evaluated heavy metal contamination in residential drinking water in Shiraz, Iran (2021). The analysis involved 80 groundwater samples collected across wet and dry seasons. Water quality was comprehensively assessed using several indices, including the heavy metals evaluation index (HEI), heavy metal pollution index (HPI), contamination degree (CD), and metal index (MI). Carcinogenic and non-carcinogenic risk assessments were conducted using deterministic and probabilistic approaches for exposed populations. In the non-carcinogenic risk assessment, the chronic daily intake (CDI), hazard quotient (HQ), and hazard index (HI) are employed. The precision of risk assessment was bolstered through the utilization of Monte Carlo simulation, executed using the R software platform. Based on the results, in both wet and dry seasons, Zinc (Zn) consistently demonstrates the highest mean concentration, followed by Manganese (Mn) and Chromium (Cr). During the wet and dry seasons, 25% and 40% of the regions exhibited high CD, respectively. According to non-carcinogenic risk assessment, Cr presents the highest CDI and HQ in children and adults, followed by Mn, As and HI values, indicating elevated risk for children. The highest carcinogenic risk was for Cr in adults, while the lowest was for Cd in children. The sensitivity analysis found that heavy metal concentration and ingestion rate significantly impact both carcinogenic and non-carcinogenic risks. These findings provide critical insights for shaping policy and allocating resources towards effectively managing heavy metal contamination in residential drinking water.

Liquid biopsy in ovarian cancer: advantages and limitations for prognosis and diagnosis.

Ovarian cancer (OC) is a highly fatal gynecologic malignancy, often diagnosed at an advanced stage which presents significant challenges for disease management. The clinical application of conventional tissue biopsy methods and serological biomarkers has limitations for the diagnosis and prognosis of OC patients. Liquid biopsy is a novel sampling method that involves analyzing distinctive tumor elements secreted into the peripheral blood. Growing evidence suggests that liquid biopsy methods such as circulating tumor cells, cell-free RNA, circulating tumor DNA, exosomes, and tumor-educated platelets may improve early prognosis and diagnosis of OC, leading to enhanced therapeutic management of the disease. This study reviewed the evidence demonstrating the utility of liquid biopsy components in OC prognosis and diagnosis, and evaluated the current advantages and limitations of these methods. Additionally, the existing obstacles and crucial topics for future studies utilizing liquid biopsy in OC patients were discussed.

Ciprofloxacin degradation by catalytic activation of monopersulfate using Mn-Fe oxides: performance and mineralization.

In this work, Mn2O3/Fe2O3 (MFO) was synthesized and used to activate monopersulfate (MPS) for the degradation of ciprofloxacin (CIP). The effect of several parameters was studied on CIP degradation. Under the optimum conditions (pH = 6.3 (natural pH), MFO = 300 mg/L and MPS = 2 mM), around 92% of CIP was decomposed. Nitrite, phosphate and bicarbonate ions had a strong inhibitory effect on the MFO/MPS process while the effect of chloride and nitrate ions was neutral. The catalytic activity of MFO was also studied by other chemical oxidants such as peroxydisulfate, periodate, hydrogen peroxide, percarbonate and peracetic acid. Scavenging tests showed that the role of sulfate radicals is more than hydroxyl radicals. MFO exhibited high catalytic activity in four recycling with insignificant leaching of Mn and Fe. During CIP oxidation, 45.5% carbon mineralization occurred and antibacterial activity of treated CIP solution was reduced. Finally, MFO/MPS was applied on actual wastewater (hospital effluent) and the results showed that MFO/MPS can be considered as a practical method for the treatment of contaminated water with emerging pollutants.

Quercetin potentiates the anti-osteoporotic effects of alendronate through modulation of autophagy and apoptosis mechanisms in ovariectomy-induced bone loss rat model.

BACKGROUND: Osteoporosis is a bone disease leading to bone fracture and affects 200 million women worldwide. Autophagy and apoptosis are two fundamental mechanisms that are involved in the development of osteoporosis. In this study we aim to investigate the combined effects of quercetin and alendronate on the markers of osteoporosis, autophagy, and apoptosis in the bone of ovariectomized rats. METHODS AND RESULTS: Fifty adult female Sprague-Dawley rats were ovariectomized and treated with alendronate alone (5 µg/kg/day) or alendronate (5 µg/kg/day) in combination with quercetin (15 mg/kg/day) for 12 weeks. Then, ELISA, stereological tests, Real-time PCR analysis, and immunofluorescence assay were used to measure the markers of osteoporosis, autophagy, and apoptosis in the serum and tibia of rats. The serum osteocalcin was significantly decreased in ovariectomized rats that received quercetin and alendronate compared with alendronate only. Stereological data showed that except for osteoclasts, the total trabecular volume, bone weight, bone volume, osteocyte, and osteoblast numbers were increased in an ovariectomized group that was treated with quercetin and alendronate compared with alendronate alone. Except for Bcl2, the autophagy markers (Beclin-1 and LC3B) and Caspase-3 were significantly downregulated in ovariectomized rats that received quercetin and alendronate compared with those treated with alendronate alone. CONCLUSION: Our results show that quercetin enhances the anti-osteoporotic effects of alendronate, possibly through the regulation of autophagy and apoptosis mechanisms. These findings suggest that the combination of quercetin and alendronate could be a useful therapeutic strategy in the treatment of osteoporosis in postmenopausal women.

The effect of natural polyphenols Resveratrol, Gallic acid, and Kuromanin chloride on human telomerase reverse transcriptase (hTERT) expression in HepG2 hepatocellular carcinoma: role of SIRT1/Nrf2 signaling pathway and oxidative stress.

BACKGROUND: There is evidence that low doses or physiological concentrations of certain natural polyphenols enhance the activity of telomerase. However, the precise mechanism by which natural polyphenols regulate telomerase activity remains unclear. Recent research indicates that NF-E2 related factor 2 (Nrf2) and silent information regulator 1 (SIRT1) are involved in human telomerase reverse transcriptase (hTERT) regulation. Thus, in order to better comprehend the mechanism by which polyphenols regulate hTERT, the present study investigated the effects of the natural polyphenols Resveratrol, Gallic acid, and Kuromanin chloride on hTERT, Nrf2, and SIRT1 expression as well as oxidative stress in HepG2 hepatocellular carcinoma. METHODS: The trypan blue dye exclusion assay was used to assess cell viability. The level of mRNA for hTERT, Nrf2, and SIRT1 was then determined using real-time PCR. A spectrophotometric analysis was conducted to quantify oxidative stress markers. RESULTS: The results demonstrated that Resveratrol induces the expression of hTERT and the SIRT1/Nrf2 pathway in a dose-dependent manner. Gallic acid at concentrations of 10 and 20 µM also increased the expression of the hTERT and SIRT1/Nrf2 pathway. Furthermore, dose-dependent overexpression of hTERT and Nrf2 was induced by Kuromanin chloride at 10 and 20 µM. Moreover, we found that Resveratrol and Kuromanin chloride ameliorated oxidative stress, whereas Gallic acid exacerbated it. CONCLUSIONS: This study demonstrates that low doses of polyphenols (Resveratrol, Gallic acid, and Kuromanin chloride) upregulate the expression of the hTERT gene in the HepG2 hepatocellular carcinoma cell line, possibly via induction of the SIRT1/Nrf2 signaling pathway. Therefore, by targeting this pathway or hTERT, the anti-cancer effect of polyphenols can be enhanced.

Effect of Lactobacillus species on apoptosis-related genes BCL2, BAX, and caspase 3 in the testes of gamma-irradiated rats.

OBJECTIVE: Ionizing radiation has various applications, including uses in medicine, industry, agriculture, and research. However, ionizing radiation is accompanied by side effects in normal radiosensitive tissues. Probiotics as natural radioprotective agents can protect normal tissues from ionizing radiation. In this regard, this study aimed to investigate the effect of Lactobacillus species on apoptosis-related genes BCL2, BAX, and caspase 3 (CASP3) in the testes of gamma-irradiated rats. METHODS: A total of 30 male Wistar rats were involved in this study. The animals received the whole- body radiation with the dose rate of 2 Gy gamma-ray and were orally gavaged with 0.2 mL of 1×1010 Lactobacillus species in phosphate-buffered saline (PBS) for 4 weeks. Then, the relative gene expression levels of BCL2, BAX, and CASP3 in the testis were assessed by using the quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Compared with the control group, radiation significantly downregulated the BCL2 and upregulated the BAX and CASP3 genes (p<0.0001). However, Lactobacillus species significantly reversed these effects. CONCLUSION: All in all, according to our results, employing Lactobacilli probiotics as a natural radioprotector may protect radiosensitive tissue from damage.

Case report: Diagnosis and emergency surgery on a young patient with extensive aortic dissection without any risk factors.

BACKGROUND: Type A aortic dissection is a very dangerous, fatal, and emergency condition for surgery. Acute aortic dissection is a rare condition, such that many patients will not survive without reconstructive surgery. CASE PRESENTATION: We present a case 24-year-old male who came with symptoms of shortness of breath and cough. The patient underwent ECG, chest radiology, and ultrasound, where the patient was found to have right pleural effusion while his ECG was normal. In the history taken from the patient, he had no underlying disease, no history of heart diseases in his family. For a better diagnosis, ETT and aortic CT angiography was performed on the patient which confirmed the evidence of dissection. Immediately after the diagnosis, necessary arrangements were made for open heart surgery and the patient was prepared for surgery. The patient was admitted in the cardiac surgery ICU for 5 days and his medication was carefully administered. After the conditions were stabilized, the patient was transferred to the post-cardiac surgery ICU ward. The patient was discharged from the hospital one week after the surgery and returned to the office as an OPD one week after his discharge. CONCLUSION: Various risk factors can play a role in creating aortic dissection. Therefore, it is necessary to pay attention to patients' history for achieving a quick and definitive diagnosis. Therefore, to control the complications of placing the cannula as well as the duration of the surgery, it is very important to reduce the duration of pumping on the patient and to be very careful during the cannula placement.

The identification of novel inhibitors of human angiotensin-converting enzyme 2 and main protease of Sars-Cov-2: A combination of in silico methods for treatment of COVID-19.

The angiotensin-converting enzyme 2 (ACE2) and main protease (MPro), are the putative drug candidates for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we performed 3D-QSAR pharmacophore modeling and screened 1,264,479 ligands gathered from Pubchem and Zinc databases. Following the calculation of the ADMET properties, molecular docking was carried out. Moreover, the de novo ligand design was performed. MD simulation was then applied to survey the behavior of the ligand-protein complexes. Furthermore, MMPBSA has utilized to re-estimate the binding affinities. Then, a free energy landscape was used to find the most stable conformation of the complexes. Finally, the hybrid QM-MM method was carried out for the precise calculation of the energies. The Hypo1 pharmacophore model was selected as the best model. Our docking results indicate that the compounds ZINC12562757 and 112,260,215 were the best potential inhibitors of the ACE2 and MPro, respectively. Furthermore, the Evo_1 compound enjoys the highest docking energy among the designed de novo ligands. Results of RMSD, RMSF, H-bond, and DSSP analyses have demonstrated that the lead compounds preserve the stability of the complexes' conformation during the MD simulation. MMPBSA data confirmed the molecular docking results. The results of QM-MM showed that Evo_1 has a stronger potential for specific inhibition of MPro, as compared to the 112,260,215 compound.