Novel formulation of parthenolide-loaded liposome coated with chitosan and evaluation of its potential anticancer effects in vitro.

BACKGROUND: In this study the formulation of parthenolide (PN), an anticancer agent extracted from a natural product, into a liposome (PN-liposome), was examined. The surface of the PN-liposome was modified using chitosan (PN-chitosome). By using real-time quantitative PCR and flow cytometry, we examined the release of PN-chitosomes, cytotoxicity, and ability to induce apoptosis in vitro. METHODS AND RESULTS: According to the present study, PN-chitosomes had a size of 251 nm which is acceptable for efficient enhanced permeation and retention (EPR) performance. PN-chitosomes were confirmed to be spherical in shape and size through FESEM analysis. In terms of encapsulation efficiency, 94.5% was achieved. PN-chitosome possessed a zeta potential of 34.72 mV, which was suitable for its stability. According to the FTIR spectra of PN and PN-chitosome, PN was chemically stable due to the intermolecular interaction between the liposome and the drug. After 48 h, only 10% of the PN was released from the PN-chitosome in PBS (pH 7.4), and less than 20% was released after 144 h. CONCLUSION: In a dose-dependent manner, PN-chitosome exhibited anticancer properties that were more cytotoxic against cancer cells than normal cells. Moreover, the formulation activated both the apoptosis pathway and cytotoxic genes in real-time qPCR experiments. According to the cytotoxicity and activating apoptosis of the prepared modified particle, PN-chitosome may be helpful in the treatment of cancer.

Preparation of the Myricetin-Loaded PEGylated Niosomes and Evaluation of their in†vitro Anti-Cancer Potentials.

Several edible plants contain flavonoids, including myricetin (Myr), which perform a wide range of biological activities. Myr has antitumor properties against various tumor cells. In this study Myr-loaded PEGylated niosomes (Myr-PN) were prepared and their anti-cancer activities were evaluated in vitro. Myr-PNs were prepared as a tool for drug delivery to the tumor site. Myr-PN was characterized in terms of size, zeta potential, and functional groups using dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), and field emission scanning electron microscopy (SEM). The Myr-PN size was 241 nm with a polydispersity index (PDI) of 0.20, and zeta potential -32.7±6.6 mV. Apoptotic properties of Myr-PN against normal and cancer cell lines were determined by flow cytometry and real-time quantitative PCR. Cancer cells showed higher cytotoxicity when treated with Myr-PN compared with normal cells, indicating that the synthesized nanoparticles pose no adverse effects. Apoptosis was induced in cells treated with 250 µg/mL of Myr-PN, in which 45.2 % of cells were arrested in subG1, suggesting that Myr-PN can induce apoptosis. In vitro, the synthesized Myr-PN demonstrated potent anticancer properties. Furthermore, more research should be conducted in vitro and in vivo to study the more details of Myr-PN anti-cancer effects.

Hyaluronic acid-coated chitosan nanoparticles as targeted-carrier of tamoxifen against MCF7 and TMX-resistant MCF7 cells.

Tamoxifen (TMX) is used to treat hormone-receptor-positive breast cancers at early stages. This research aimed to assess the potential of NPs in targeted delivery of TMX against MCF7 and TMX-resistant MCF7 breast cancer cell lines. For this purpose, a targeted delivery system including chitosan NPs coated with hyaluronic acid (HA-CS NPs) was created and examined in vitro. Chitosan NPs were first fabricated and loaded with TMX using the ionic-gelation method to prepare a drug-delivery system. Then, TMX-loaded CS NPs were coated by crosslinking the amino groups of chitosan to the carboxylic group of hyaluronic acid. The developed TMX delivery system was then optimized and characterized for particle fabrication, drug release, and targeting against cancer cells. The HA-CS particle size was 210 nm and its zeta potential was +25 mv. The encapsulation efficiency of TMX in NPs was 55%. TMX released from the NPs in acidic pH (5-6) was higher than the physiological pH (7.4). The cytotoxic effect of TMX-loaded HA-CS NPs on MCF7 and TMX-resistant MCF7 cells was significantly higher than TMX-loaded CS NPs and free drug. The findings confirmed the significant suppressive impact of TMX-loaded HA-CS NPs on MCF7 and TMX-resistant MCF7 cancer cells compared to the TMX-loaded CS NPs and free TMX. Graphical abstract.

Resveratrol supplementation improves DNA integrity and sperm parameters in streptozotocin-nicotinamide-induced type 2 diabetic rats.

Reproductive dysfunction is one of the diabetes complications. Resveratrol, a polyphenol compound, shows antidiabetic and antioxidant effects. The aim of the present study was to investigate the protective effects of resveratrol on sperm parameters and chromatin quality in experimentally induced type 2 diabetes by streptozotocin and nicotinamide. Forty male adult Wistar rats were grouped into normal control, diabetic control and resveratrol-treated diabetic groups (1, 5 and 10 mg/kg orally treated for 30 days). Type 2 diabetes was induced using a single dose of streptozotocin and nicotinamide by intraperitoneal injection. Then, the different parameters and chromatin condensation of the epididymal extracted spermatozoon were studied using aniline blue (AB), acridine orange (AO) and toluidine blue (TB) staining. The sperm parameters including count, motility and viability had significant reduction in diabetic rats (p < 0.05). Resveratrol increased count, motility and viable spermatozoa relative to the diabetic group (p < 0.05). The mean percentage of AB, AO and TB staining positive spermatozoa was increased in diabetic groups compared to control (p < 0.001) and decreased after treatment with 1 and 5 mg/kg resveratrol (p < 0.001). The results of AO and TB staining showed that resveratrol did not have any beneficial effect on chromatin condensation and denatured DNA at the dose of 10 mg/kg.

Co-administration of resveratrol and beta-aminopropionitrile attenuates liver fibrosis development via targeting lysyl oxidase in CCl4-induced liver fibrosis in rats.

Objectives: In the current study, we aimed to investigate the effect of administration of resveratrol (RES) and beta-aminopropionitrile (BAPN) separately and together on the liver fibrosis progression via regulation of the gene expression and protein level of lysyl oxidase (LOX).Materials and methods: The six-week old Wistar rats received carbon tetrachloride (CCl4) intraperitoneally and RES and BAPN were administrated orally for eight weeks. The hepatoprotective effects of RES, BAPN, and combination treatment were evaluated. Then the hepatic protein and gene expression levels of LOX were measured.Results: Both RES and BAPN showed the antifibrotic effect through the reduction of collagen fiber bundles, hepatic hydroxyproline content, and protein level of LOX. The antifibrotic effect increased when RES and BAPN up-taken together.Conclusion: The co-administration of RES and BAPN can be considered as a promising therapeutic approach via targeting LOX.

Study of Insulin-Loaded Chitosan Nanoparticle Effects on TGF-ß1 and Fibronectin Expression in Kidney Tissue of Type 1 Diabetic Rats.

In diabetes, the increasing blood glucose levels through oxidative stress, with increase in inflammatory cytokines and growth factors, such as TGF-ß1, can cause long-term complications, including nephropathy. Subcutaneous injection of insulin is a common method used to treat Type 1 diabetes, which can lead to problems such as hypoglycemia and edema. In the present study, we examined the effect of insulin in its two injectable and oral forms on the expression of TGF-ß1 and fibronectin in kidney tissue of STZ diabetic rats. A total of 25 male Wistar rats were randomly divided into 5 groups: C: normal control, D: diabetic control, D+NP, oral insulin-loaded trimethyl chitosan nanoparticles (8 IU/kg), and subcutaneously injected insulin (8 IU/kg). The groups were treated from 8th to 10th weeks. After 10 weeks, FBS was measured. Also, the TGF-ß1 and fibronectin mRNA expression and serum TGF-ß1 protein were examined in the kidney tissue. Structural changes in the kidney tissue were studied using H&E staining. After 10 weeks of diabetes induction, the rats showed significant change in blood glucose, weight, serum TGF-ß1, Fibronectin and TGF-ß1 expression of kidney in diabetic groups (p < 0.05). Oral insulin-loaded trimethyl chitosan nanoparticles treatment, similar to injected insulin, significantly ameliorate blood glucose and rats' weight (p < 0.05). However, the reduction in fibronectin and TGF-ß1 expression and serum TGF-ß1 protein by both treatments was not statistically significant (p > 0.05). These data showed that oral insulin-loaded trimethyl chitosan nanoparticles were better therapeutic intervention than injected insulin for Type 1 diabetes.

Salivary and Serum Antioxidant and Oxidative Stress Markers in Dental Caries.

Dental caries is the most common, chronic, noncommunicable, preventable oral disease worldwide. Oxidation may play an important role in dental caries initiation and progression. Antioxidants in body fluids protect cells. The aim of this study was to evaluate salivary and serum total antioxidant capacity (TAC) and malondialdehyde (MDA) levels in dental caries. A total of 118 healthy caries-free and caries-active male and female students participated. Caries was detected clinically. Unstimulated whole-saliva samples and blood samples were obtained. Sialochemical analysis was carried out by spectrophotometric assay. Data were analyzed with the Student t test using STATA 11. Salivary and serum TAC levels in the case and control groups did not show any significant differences. Mean salivary MDA levels in the case and control groups were 0.71 ± 0.1 and 0.35 ± 0.06 nmol/mL, respectively. The results showed significantly higher levels of salivary and serum MDA in the case group compared to the healthy control group. The oxidative stress marker was significantly higher in the caries group compared to the healthy control group. Antioxidants were not significantly different between the two groups. MDA can be produced by dental caries, resulting in a decrease in antioxidant levels, causing disease progression. Further studies are necessary to determine whether MDA is the cause or effect of the disease.

Role of resveratrol in the management of insulin resistance and related conditions: Mechanism of action.

Resveratrol (RES), a well-known antioxidant, is present in numerous plant species and, as a result, is easily obtained through dietary intake of plant-based foods and beverages. Several studies suggest that RES has anti-carcinogenic, anti-microbial, and anti-viral effects. It may also have beneficial metabolic properties that result in mitigation of insulin resistance (IR) and related metabolic abnormalities, including dyslipidemia, hyperglycemia, and hyperinsulinemia through regulation of gene expression or the activity of rate-limiting enzymes. A large body of evidence supports the beneficial effects of RES in the management and treatment of IR, type 2 diabetes, and related complications through a multitude of mechanisms. This review article focuses on the mechanisms of action of RES, the mechanisms leading to improved insulin sensitivity, and its clinical role in the management and treatment of type 2 diabetes.

Evaluation of salivary catalase, vitamin C, and alpha-amylase in smokers and non-smokers: a retrospective cohort study.

BACKGROUND: Saliva and its defence systems such as antioxidants and minerals are very important in the pathogenesis of different diseases. Cigarette smoking has many destructive effects. Oxidative stresses play an important role in the side effects of smoking. This study assessed the effect of cigarette smoking on salivary levels of catalase, vitamin C, and α-amylase. METHODS: This retrospective cohort study was carried out in Hamadan, Iran, on 510 subjects; 259 subjects were smokers (the exposed group) and 251 were non-smokers (the unexposed group). Five microliters of unstimulated saliva was collected by spitting method. Catalase, vitamin C, and α-amylase salivary levels were determined by spectrophotometric assay. Data were analyzed with t-test using STATA 12. RESULTS: Vitamin C level in smokers was significantly lower than that in non-smokers. The salivary catalase levels were lower and α-amylase levels were higher in smokers, but the differences were not statistically significant (P = 0.416 and P = 0.265, respectively). Smokers were younger than non-smokers. CONCLUSION: Smoking resulted in a change in salivary antioxidant levels. Changes in antioxidant levels can influence the deleterious effects of smoking on oral mucosa; it might also indicate systemic changes and changes in the serum levels of oxidative agents. Further studies are necessary to understand the mechanisms and real effects of smoking, to determine the benefits of supplementary antioxidants for treatment and to reduce the dangerous side effects of smoking.

Salusin-α Attenuates Inflammatory Responses in Vascular Endothelial Cells.

Atherosclerosis accounts for numerous cardiovascular diseases, and cytokines have a critical role in acceleration or suppression of disease. Salusin-α presents a new class of bioactive peptides that can have anti-atherogenic properties. Therefore, the effects of salusin-α on the expression of some pro- and anti-inflammatory cytokines and on TNF-α-induced inflammatory responses in human umbilical vein endothelial cells (HUVECs) were examined. The involvement of the NF-κB pathway in effects of salusin-α in HUVECs was checked using Bay 11-7082 as an NF-κB inhibitor. The mRNA expression of pro-inflammatory cytokines including IL-6, IL-8, and IL-18 and anti-inflammatory cytokine IL-1Ra was assessed by real-time PCR. The protein levels of cytokines were measured by the ELISA method. Salusin-α suppressed both mRNA and protein expression of pro-inflammatory cytokines and induced mRNA and protein expression of IL-1Ra in HUVECs. Salusin-α suppressed TNF-α-induced inflammatory responses in HUVECs. The down-regulatory or up-regulatory effects of salusin-α on expression of cytokines could not be influenced by Bay 11-7082 pretreatment. Our findings indicate anti-inflammatory effects of salusin-α and suggest a novel peptide-based therapeutic strategy for atherosclerosis.

Beneficial Effect of Aqueous Garlic Extract on Inflammation and Oxidative Stress Status in the Kidneys of Type 1 Diabetic Rats.

One of the most important complications of diabetes is nephropathy. This study investigates the effects of aqueous garlic extract on inflammation and oxidative stress status in the kidneys of diabetic rats. Male rats were divided into four groups- control rats, diabetic rats, garlic extract-treated diabetic rats, garlic extract-treated normal rats. The glucose, urea, uric acid, and creatinine levels were measured in sera using colorimetric methods. To determine the oxidative stress condition in the kidney tissues, total antioxidant capacity (TAC), malondialdehyde (MDA), and total oxidant status (TOS) were measured using colorimetric methods. Inflammation status was evaluated by the determination of tumor necrosis factor-alpha (TNF-α) gene and protein expression using qRT-PCR and ELISA respectively, while nitric oxide (NO) level in these tissues was measured using the Griess method. Histological examination of Kidneys was carried out by H&E staining. The levels of glucose, urea, and uric acid were found to increase in the serum of diabetic rats and decrease in that of diabetic rats after treatment with garlic. Measurement of MDA, TOS, and TAC revealed oxidative stress in diabetic rats, which improved after receiving the extract. The NO and TNF-α protein levels in diabetic rats were higher than those in control rats. After treatment with garlic, the levels of TNF-α protein and NO became close to the normal levels. Histological results confirmed certain other data as well. Garlic has antioxidant properties; therefore, it can reduce oxidative stress, which plays an important role in the development of diabetic nephropathy. Reduction in oxidative stress has beneficial effects on inflammation because it leads to a decrease in the level of TNF-α.

Effects of Resveratrol on Receptor for Advanced Glycation End Products (RAGE) Expression and Oxidative Stress in the Liver of Rats with Type 2 Diabetes.

Incidence of diabetes mellitus is dramatically growing in the world. Oxidative stress, advanced glycation end products (AGEs) and receptor for AGE (RAGE) play key role in the pathogenesis of diabetes. Little is known about resveratrol effects on the liver. We hypothesize that resveratrol may exert a hepatoprotective effect in diabetic rats. Male rats with diabetes were treated with or without resveratrol at 1, 5 and 10 mg/kg body weight for 30 days. Total AGEs and malondialdehyde (MDA) levels in liver tissues were determined by spectrofluorimetric methods. Total antioxidant capacity and total oxidant contents in the liver and glucose in plasma were measured by a colorimetric assay. Expression of RAGE was assayed in liver of all animals using quantitative polymerase chain reaction. In liver tissue extract of resveratrol-treated rats with diabetes, MDA levels, total oxidant, plasma glucose and expression of RAGE were significantly reduced compared to the untreated group. Moreover, total antioxidant levels were significantly increased in treated rats. There was no significant difference in AGE contents among all groups. These results revealed that resveratrol had beneficial effects on the liver by extenuating oxidative stress and down regulation of RAGE expression.

Aqueous Extract of Anethum Graveolens L. has Potential Antioxidant and Antiglycation Effects.

The aim of this study was to assess the antiglycation and antioxidant properties of aqueous extract of Anethum graveolens (dill). In the in vivo and in vitro experiments, antioxidant properties, blood glucose, and AGEs formation were determined. Dill extract was given orally to healthy and diabetic rats. Our results illustrated that different concentrations of dill extract (0.125, 0.25, 0.5, and 1 mg/ml) have potential antiradical and antioxidant activity. Aqueous extract of dill significantly reduced AGEs formation and fructosamine levels, protein carbonyl and also thiol group's oxidation, amyloid cross-ß and fragmentation. After 2 months, blood glucose levels (P=0.006) and AGEs formation (P=0.003) significantly reduced in dill treated group compared with untreated diabetic animals. In conclusion, dill can be recommended as herbal medicine for the control and prevention of diabetic complications.

Effect of Resveratrol Supplementation on the SNARE Proteins Expression in Adipose Tissue of Stroptozotocin-Nicotinamide Induced Type 2 Diabetic Rats.

BACKGROUND: Glucose uptake by muscles and fat cells is carried out by the GLUT4 system. Isoforms of the SNAP23, syntaxin-4 and VAMP-2 play an important role in regulating GLUT-4 trafficking and fusion in adipocytes. The changes of SNARE proteins levels and thus impaired GLUT-4 displacement can be one of the etiological causes of type 2 diabetes. Due to changes in the expression of these proteins in diabetes, the aim of this study was to investigate the effect of the natural compound resveratrol with anti-diabetic properties on impaired expression of SNARE proteins in type 2 diabetes. METHODS: Forty male Wistar rats were used in this study. Type 2 diabetes was induced by administering a single dose of streptozotocin and nicotinamide. The expression of SNAP-23, syntaxin-4 and VAMP-2 proteins were assessed using real-time qRT-PCR. Also, some biochemical parameters were examined, including fasting blood glucose, insulin levels and insulin resistance. RESULTS: The results of this study showed that, resveratrol supplementation increased blood insulin level, reduced the fasting blood glucose, and improved the insulin resistance. In addition, resveratrol supplementation increased the expression of SNAP-23, syntaxin-4 and VAMP-2 proteins that involved in GLUT-4 transport in adipose tissue of diabetic rats. CONCLUSION: Final results showed that SNARE proteins expression is significantly reduced in diabetic rats and treatment with resveratrol supplementation is associated with the increased expression of these proteins.

An optimized protocol for overproduction of recombinant protein expression in Escherichia coli.

The gram-negative bacterium Escherichia coli (E. coli) offers a means for rapid, high-yield, and economical production of recombinant proteins. Here, a protocol for optimization of parameters involved in bacterial expression conditions is described. L-Asparaginase (ASNase II) was chosen as a model protein for our experiments. ASNase II gene (ansB) was cloned into the pAED4 plasmid and transformed into E. coli BL21pLysS (DE3)-competent cells. It was assumed that high cell density and high copy number of recombinant plasmid in the bacteria host could result in very high production of the recombinant protein. Circumstances for the overproduction of recombinant ASNase II including cell growth conditions, isopropyl ß-D-1-thiogalactopyranoside (IPTG) level, ampicillin (Amp) concentration before and during IPTG induction, and cell density were optimized. Regarding the final optimization, overexpression of ASNase II was assessed on a large scale in LB medium. Periplasmic ASNase II was extracted using an alkaline lysis method. The extracted protein was purified by one-step DEAE-Sepharose fast-flow chromatography. ASNase II activity was considered an index for the protein expression. Applying the optimized practical protocol, protein production was significantly enhanced in comparison to the traditional IPTG induction method in the absence of a fermentor and can be applied for overexpression of other recombinant proteins.

The Lawson-loaded ß-cyclodextrin nanocarriers (LB-NCs) a novel targeted cancer cell in stomach and breast cancer as a drug delivery system.

Applying nanotechnology to design drug delivery systems is a promising turning point in cancer treatment strategies. In the current study, Lawson, a nonpolar anticancer phytochemical, was entrapped into ß-cyclodextrin polymer to evaluate its selective cytotoxicity in several types of human cancer cell lines including MCF-7, AGS, A549, and PC3. The Lawson-loaded ß-cyclodextrin nanocarriers (LB-NCs) were produced by applying a high-energy ultrasound-mediated homogenization technique. The LB-NCs were characterized by applying dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), zeta potential, and field emission scanning electron microscopy (FESEM) analysis. Also, the selective cytotoxic impact of the LB-NCs was studied by conducting the MTT assay on human MCF-7, AGS, A549, and PC3 cancer cell lines. Finally, the type of cellular death was evaluated by measuring the cell cycle status and apoptotic gene expression profile of the treated MCF-7 cells by conducting flow cytometry and Q-PCR methods, respectively. The synthesized negatively charged (- 23.8 mV) nanoparticles (348.12 nm) exhibited apoptotic activity in the human breast MCF-7 cancer cells by upregulating the apoptotic gene expression profile (Caspase 3, 8, and 9). The LB-NCs exhibited a significant selective cytotoxic effect on the human cancer cell lines compared with the normal HUVEC cells. However, variable toxic intensities were detected depending on the cancer cell type. Selective cancer cell-depended anticancer activity of the produced LB-NCs has the potential to be considered their safe efficient targeted anticancer activity. However, studying the animal cancer models has to be conducted to verify their selective toxicity and clarify the cellular death mechanism.

The silibinin-loaded Zein-ß cyclodextrin nano-carriers (SZBC-NCs) as a novel selective cancer cell drug delivery system in HT-29 cell line.

Entrapping phytochemical bioactive compounds into nano-structured biocompatible polymers has been successfully utilized for improving cancer treatment efficiency. Silibinin is a potent compound that shows promising anticancer properties. In the present study, the Zein-ß-cyclodextrin complex was used to encapsulate silibinin and evaluate the induced cell death type and cytotoxic impacts on human cancer cells. The silibinin-loaded Zein-ß cyclodextrin nano-carriers (SZBC-NCs) were synthesized utilizing a gradual ultrasound-mediated homogenization technique and characterized by Zeta potential, DLS, FESEM, and FTIR analysis. The SZBC-NCs' antioxidant activity was studied by conducting ABTS and DPPH radical scavenging assays. Finally, the SZBC-NCs selective toxicity and cellular death induction mechanism were studied on the HT-29 and AGS cancer cells by measuring the cell survival and apoptotic gene (Caspase 3, 9), respectively, which were verified by conducting the DAPI staining analysis. The negatively charged (- 27.47 mV) nanoparticles (286.55 nm) showed significant ABTS and DPPH radical scavenging activity. Moreover, the remarkable decrease in the IC50 concentrations of the SZBC-NCs among the HT-29 and AGS cancer cell lines exhibited their selective cytotoxic potential. Also, the overexpressed apoptotic (Caspases 3 and 9) and down-regulated necrotic (NFKB) gene expressions following the SZBC-NCs treatment doses indicated the apoptotic activity of SZBC-NCs, which were verified by the increased apoptotic morphology of the DAPI-stained HT-29 cancer cells. The antioxidant and colon cancer cell-related apoptotic activity of the SZBC-NCs make it an appropriate anti-colon cancer nano delivery system. Therefore, they can potentially be used as a safe efficient colon cancer treatment strategy. However, further in vivo experiments including animal cancer models have to be studied.

A novel nanoformulation of parthenolide coated with polydopamine shows selective cytotoxicity and induces apoptosis in gastric cancer cells.

An anticancer agent derived from a natural product, parthenolide (PN), was studied to formulate PN into poly(lactic-co-glycolic acid) (PLGA). Polydopamine (PDA) was employed to modify the surface of PN-PLGA. Following characterization, the PN-PLGA-PDA was evaluated for its in vitro release, cytotoxicity, and ability to induce apoptosis using flow cytometry and real-time quantitative PCR. According to the present study, PN-PLGA-PDA had a size of 195.5 nm which is acceptable for efficient enhanced permeation and retention (EPR) performance. The SEM results confirmed the size and spherical shape of the nanoparticles. The percentage of encapsulation efficiency was 96.9%. The zeta potential of PN-PLGA-PDA was - 31.8 mV which was suitable for its stability. FTIR spectra of the PN-PLGA-PDA indicated the chemical stability of the PN due to intermolecular hydrogen bonds between polymer and drug. The release of PN from PN-PLGA-PDA in PBS (pH 7.4) was only 20% during the first 48 h and less than 40% during 144 h. PN-PLGA-PDA exhibited anticancer properties in a dose-dependent manner that was more cytotoxic against cancer cells than normal cells. Moreover, real-time qPCR results indicated that the formulation activated apoptosis genes to exert its cytotoxic effect and activate the NF-kB pathway. Based on our findings, PN-PLGA-PDA could serve as a potential treatment for cancer.

Effects of ascorbic Acid on serum level of unconjugated estriol and its relationship with preterm premature rupture of membrane: a double-blind randomized controlled clinical trial.

BACKGROUND: Vitamin C is a water-soluble antioxidant that not only stimulates and protects collagen synthesis but also plays an important role in maintaining cellular integrity in a normal pregnancy. This study surveyed the effects of ascorbic acid on the serum level of unconjugated estriol and the relationship between unconjugated estriol and preterm premature rupture of membrane (PPROM). METHODS: This double-blind, randomized clinical trial recruited 60 patients with predisposing factors to PPROM. The women were randomly divided into two groups of intervention and control and received vitamin C and placebo, respectively. The intervention group received 250 mg vitamin C twice a day and the controls received the placebo only. Unconjugated estriol was measured using the ELISA. All data were extracted and recorded in a checklist and compared using descriptive statistics as well as the x (2), Fisher exact, and t tests. RESULTS: The demographic data showed no difference between the two groups. The mean level of serum unconjugated estriol was significantly lower in the intervention group than in the control group (P=0.044). Also, the frequency of PPROM was lower in the intervention group, but the difference was not significant (P>0.05). Unconjugated estriol levels were not significantly different between the healthy women and the PPROM patients. CONCLUSION: This study demonstrated that vitamin C administration decreased unconjugated estriol levels in the patients with PPROM. The findings of this study also indicated that administration of ascorbic acid was a safe and effective method to reduce the incidence of PPROM. Alteration in unconjugated estriol is an active mediator for this effect.

Relationship Between Human FCγRIIA rs1801274 G Allele and Risk of Death Among Different SARS-CoV-2 Variants.

Coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and spread very quickly across the world. Different responses to infections have been related to fragment crystallizable gamma-receptor II alpha (FcγRIIA) polymorphisms. The purpose of this investigation was to determine if FCγRIIA rs1801274 polymorphism was related to COVID-19 mortality among different variants of SARS-CoV-2. The FCγRIIA rs1801274 polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism technique in 1,734 recovered and 1,450 deceased patients. Deceased patients had significantly higher minor allele frequency of the FCγRIIA rs1801274 G allele than in the recovered cases. The COVID-19 mortality was associated with FCγRIIA rs1801274 GG and AG genotypes in the Delta variant and with FCγRIIA rs1801274 GG genotypes in the Alpha and Omicron BA.5 variants. The reverse transcription-quantitative polymerase chain reaction Ct values revealed statistically significant differences between individuals with a G allele and those with an A allele. In conclusion, among the several SARS-CoV-2 variants, there may be a correlation between the mortality rate of COVID-19 and the G allele of FCγRIIA rs1801274. To confirm our findings, thorough research is still required.