Oral administration of encapsulated catechin in chitosan-alginate nanoparticles improves cognitive function and neurodegeneration in an aluminum chloride-induced rat model of Alzheimer's disease.

The present study aimed to investigate the effect of catechin-loaded Chitosan-Alginate nanoparticles (NPs) on cognitive function in an aluminum chloride (AlCl3)-induced rat model of Alzheimer's disease (AD). The Catechin-loaded Chitosan-Alginate nanocarriers were synthesized through ionotropic gelation (IG) method. Physio-chemical characterization was conducted with the Zetasizer Nano system, the scanning electron microscope, and the Fourier transform infrared spectroscopy. The experiments were performed over 21 days on six groups of male Wistar rats. The control group, AlCl3 treated group, Catechin group, nanocarrier group, treatment group 1 (AlCl3 + Catechin), and treatment group 2 (AlCl3 + nanocarrier). A behavioral study was done by the Morris water maze (MWM) test. In addition, the level of oxidative indices and acetylcholine esterase (AChE) activity was determined by standard procedures at the end of the study. AlCl3 induced a significant increase in AChE activity, along with a significant decrease in the level of Catalase (CAT) and total antioxidant capacity (TAC) in the hippocampus. Moreover, the significant effect of AlCl3 was observed on the behavioral parameters of the MWM test. Both forms of Catechin markedly improved AChE activity, oxidative biomarkers, spatial memory, and learning. The present study indicated that the administration of Catechin-loaded Chitosan-Alginate NPs is a beneficial therapeutic option against behavioral and chemical alteration of AD in male Wistar rats.

The Relationship between VDR Gene Polymorphisms Bsm1 and Apa1 with Breast Cancer Risk.

Background In addition to its multifaceted physiological functions, vitamin D is recognized for its protective role against cancer. To manifest its effects, vitamin D engages with the vitamin D receptor ( VDR ) gene responsible for its encoding. Investigations have unveiled that polymorphisms within the VDR gene exert influence over the expression and/or functionality of the VDR protein. Notably, certain VDR gene polymorphisms have emerged as particularly pertinent in the context of tumorigenesis, including Fok1 (rs2228570), Bsm1 (rs1544410), Taq1 (rs771236), and Apa1 (rs7975232). This study aims to scrutinize the correlation between the Bsm1 and Apa1 polymorphisms and the susceptibility to breast cancer development. Materials and Methods In this study, 50 patients suffering from breast cancer with less than 6 months breast cancer diagnosis and 50 healthy control individuals have been chosen. Restriction fragment length polymorphism polymerase chain reaction was used to determine the genotype of polymorphisms. Results The results of the statistical analysis showed that among the studied polymorphisms, there was no correlation with the development of breast cancer. Conclusion Studies on various cancers have produced inconsistent results regarding vitamin D's role in the development and progression of cancer. Therefore, further research is necessary to determine vitamin D's role in cancer development and progression.

The inhibitory effect of PLGA-encapsulated berberine on hepatotoxicity and α-smooth muscle actin (α-SMA) gene expression.

BACKGROUND: Liver injury results in excessive extracellular matrix (ECM) deposition in the liver, which is mainly produced by hepatic stellate cells (HSC). Alpha-smooth muscle actin (α-SMA) and liver enzymes are the two hallmarks of liver injury. Previously, it has been confirmed that berberine (BBR) attenuates liver injury. This study aimed to investigate the protective effect of Poly Lactic-co-Glycolic Acid (PLGA) encapsulated BBR against liver injury. METHODS: Nanoprecipitation, encapsulation, and physio-chemical characterization of BBR-PLGA nanoparticles (BBR-PLGA-NP) have been done. The protective effects of BBR-PLGA-NPs and BBR against carbon tetrachloride (CCl4)-treated Wistar rats were investigated. The serum levels of alanine aminotransferase and aspartate transaminase were measured, and the expression level of α-SMA was quantified by qRT-PCR. To evaluate the liver changes, morphological and histological staining was done. RESULTS: BBR-PLGA-NPs markedly reduced serum ALT and AST in rats treated with CCl4. Although the expression level of α-SMA was downregulated in the CCl4-injected rats that were treated with BBR, α-SMA expression in this group was still remarkably higher than the control group. α-SMA mRNA was significantly under-expressed (p < 0.05) by BBR-PLGA-NPs and the hepatic histology revealed BBR-PLGA-NPs made further improvements than free BBR. CONCLUSION: The use of nanoparticle to encapsulate BBR is a worthy approach to enhance the curative effect of BBR against liver injuries, which donate a safe and effective drug delivery strategy to treat liver injuries.

Long-term exposure to electromagnetic radiation from mobile phones can cause considerable changes in the balance of Bax/Bcl2 mRNA expression in the hippocampus of mice.

The aim of the present study was the investigation of the effects of mobile phones at different daily exposure times on the hippocampal expression of two apoptotic genes. Forty-eight male BALB/c mice were randomly divided into six groups with 8 animals in each group. Four experimental groups were respectively exposed to electromagnetic waves for 0.5, 1, 2 and 4 hours twice a day for 30 consecutive days. One experimental group was radiated for 4 hours once a day, while the control group did not receive any radiation during the experiment. The expression of both Bax and Bcl2 mRNAs was upregulated in the mice exposed for one and two hours. Whilst the highest expressions were observed in the two-hours radiation in the exposed group, the expression of both studied genes was downregulated in animals with longer exposure to radiation in a duration-dependent manner. The highest ratio of Bax/Bcl2 expression was observed in the mice that received radiation for four hours twice a day. These results revealed that mobile phone radiation can cause considerable changes in the balance of Bax/Bcl2 mRNA expression in laboratory mice hippocampus.

Diagnostic value of cytology in oral ulcer and comparison with histopathology and direct immunofluorescence.

Rapid diagnosis of pemphigus vulgaris (PV) is an important task in patient's prognosis and treatment. Although PV is routinely diagnosed through investigation of pathology specimens and direct immunofluorescence assays, Tzanck smear can be used as rapid, inexpensive, and easily used test to confirm its clinical diagnosis. This study aimed to determine the diagnostic value of Tzanck smear in erosive oral lesions of PV and also determine its sensitivity and specificity for diagnostic purposes. A total of 68 patients with erosive/ulcerated oral lesions were included in this study and divided into PV (case group) vs other causes of erosive oral lesions (control group). From all participants, two Tzanck smears were prepared for both Giemsa and hematoxylin-eosin (H&E) staining. For definite diagnosis, histopathology and direct immunofluorescence evaluations were performed based on clinical findings. The sensitivity of acantholytic cells in Tzanck smear of erosive oral lesions of PV cases was 80.5% (for both Giemsa and H&E staining), whereas specificity values of Giemsa and H&E staining were 84.6% and 96.3%, respectively. Based on our findings, the Tzanck smear of erosive oral lesions is a simple, quick, and inexpensive test for screening and primary diagnosis of PV.

Induction of a Robust Humoral Response using HIV-1 VLPMPER-V3 as a Novel Candidate Vaccine in BALB/c Mice.

BACKGROUND: Several approaches have not been successful to suppress HIV (Human immunodeficiency virus) infection among infected individuals or to prevent it yet. In order to expand strong HIV specific humoral and cellular responses, Virus-like particles (VLPs) as potential vaccines show significant increase in neutralizing antibodies secretion, T-cell count and also secretion of cytokines. OBJECTIVE: This study aimed at immunological evaluation of VLPs harboring high copy of MPERV3 in BALB/c mice. METHODS: Female BALB/c mice were immunized with homologous and heterologous primeboosting regimens of HIV-1 VLPMPER-V3. Their immune responses were evaluated for humoral responses (Total IgG and IgG isotyping) and cellular responses (IFN-γ, IL-5 secretion, in vitro CTL assay and T cell proliferation) and compared in immunized mice. RESULTS: The data showed robust induction of humoral response in mice groups which received different regimens of VLP. Furthermore, analysis of cytokine profile indicated that the highest IL-5 secretion was related to VLP+M50 group and confirmed the dominance of Th2 immunity in this group. CONCLUSION: This study showed that VLP MPER-V3 as a potential vaccine candidate has the potency as an effective prophylactic vaccine and this finding guarantees further investigations to achieve a promising HIV-1 vaccine candidate.

Comprehensive analysis of oxidative stress markers and antioxidants status in preeclampsia.

Preeclampsia is a hypertensive disorder in pregnant women, which can be the leading cause of maternal and neonatal death or premature birth. Although the cause of preeclampsia is still not clear, local or systemic oxidative stress may explain the pathological features associated with this complication. However, it is not clear whether oxidative stress is the cause or the result of preeclampsia. For this purpose, the present meta-analysis was intended to evaluate the oxidant and antioxidant status in women with preeclampsia. Relevant studies were identified after a preliminary investigation of research articles published up to September 2017. In the overall analysis, including 2953 cases and 3621 controls, a statistically significant reduction in total antioxidant capacity, nitric oxide, superoxide dismutase, glutathione, vitamin E and C was observed in preeclampsia women. On the other hand, a statistically significant increase in malondialdehyde, protein carbonyl, total peroxide, glutathione peroxidase, catalase and uric acid were observed in preeclampsia women. The increased products of oxidative stress, which were found in the present meta-analysis might be an underlying mechanism for endothelial dysfunction in preeclampsia. This meta-analysis provides a scientific support that primary reduction of antioxidant capacity and increased levels of oxidative stress products may induce a condition in which the pathways responsible for blood pressure homeostasis are disrupted. In conclusion, it is hypothesized when oxidative stress is established, a protective response is induced by increasing some antioxidants. Further studies are warranted to investigate the role of dietary supplementation and genetic variation in women with different ethnicity.

Construction and Production of HIV-VLP Harboring MPER-V3 for Potential Vaccine Study.

BACKGROUND: Vaccine against HIV-1 is not currently available. In present, Virus like particles (VLPs) as effective strategy was used in several vaccine developing. Two conserved sequences; V3 loop of gp120 and the membrane-proximal external region (MPER) of gp41 are dominant sites for vaccine studies. OBJECTIVE: In this study, we used fusion gene of MPER and V3 to product recombinant VLPs and introduced a novel retroviral VLPs harboring high copy of MPER-V3 for HIV-1 vaccine design. METHODS: The pEGFP-N1 plasmid harboring MPER-V3 sequence with Vpr linker was constructed. To produce virus-like particles, HEK 293T cells were co-transfected with the recombinant plasmid, pSPAX-2, pMD2-G and pWPXLd plasmids, evaluated by AFM and SEM microscopy and quantified using P24 end-point ELISA assay. RESULTS: Time-course quantification of p24 protein as the characteristics of viral production evidenced for the efficient secretion of virus-like structures (up to 120 ng/ml) to the culture supernatant of transfected cells. Examination of the centrifuge-concentrated VLPs by AFM and SEM microscope, also illustrated particles with spherical morphologies and diameters of around 150 nm that had similar sizes to HIV virions. CONCLUSION: These data indicated the production of HIV-1 virus-like particles harboring high copy of MPER-V3 that maintained their antigenic structure. These VLPs represented a good implication as a potential vaccine candidate and this guarantees the further investigations towards the assessment of its immunogenicity.

Catechol-O-methyltransferase Gene Polymorphism (Val158Met) and Development of Pre-eclampsia.

OBJECTIVES: Catechol-O-methyltransferase (COMT) is a key enzyme in degradation pathways of estrogens and catecholamines. The present meta-analysis was done to elucidate the association of COMT Val158Met polymorphism with pre-eclampsia among pregnant women. METHODS: A literature search was conducted in electronic databases including PubMed, Scopus, Elsevier, Springer and Google Scholar to find eligible studies. The pooled odds ratios (ORs) with 95% confidence intervals were calculated under dominant, recessive, co-dominant, and allelic models. RESULTS: This meta-analysis included 6 eligible studies consisting 2596 cases and 4223 controls. The ORs for the COMT G472A polymorphism and pre-eclampsia were indicative of positive association under several genetic models. The results indicated that COMT Val158Met polymorphism was significantly associated with the increased risk of pre-eclampsia in recessive model (AA vs. AG + GG: OR = 1.522 [95% CI: 1.089-2.127]; p = 0.014), co-dominant model (AA vs. GG: OR = 1.605 [95% CI: 1.102-2.336]; p = 0.014), and allelic model (A vs. T: OR = 1.200 [95% CI: 1.021-1.402]; p = 0.021). CONCLUSIONS: In summary, COMT Val158Met polymorphism is positively associated with the increased risk of pre-eclampsia among pregnant women, especially the homozygous carriers. It could be of value to investigate its association with pre-eclampsia in combination with additional risk factors. However, very large studies with different ethnic population are required to accurately demonstrate the role of this candidate gene in development of pre-eclampsia.

Fate and mass balance of triclosan and its degradation products: Comparison of three different types of wastewater treatments and aerobic/anaerobic sludge digestion.

Triclosan (TCS) as an antimicrobial agent has been ubiquitously found in wastewater and sewage sludge. TCS may undergo transformation/degradation during wastewater treatment. Some of the resulted products such as 2,4-dichlorophenol (2,4-DCP), 2,8-dichlorodibenzoparadioxin (2,8-DCDD) and methyl triclosan (MTCS) are presumed toxic/persistent compounds. In this study, fate of TCS and the probability of formation of important degradation products were investigated in three susceptible wastewater/sludge treatment practices. 24.1% and 27.2% of the loading TCS was adsorbed to the generated sludge, whereas up to 60% of the loading TCS was biotransformed. Up to 9.9% and 13.0% of TCS loss was attributed to the formation of 2,4-DCP and 2,8-DCDD in chlorination and UV disinfection, respectively. Anaerobic and aerobic sludge digestion processes eliminated up to 23.0% and 56.0% of TCS, respectively. About 7.4% of TCS in aerobic digestion was transformed to methyl triclosan (MTCS). Significant temporal variation of TCS was observed in primary sedimentations, except for chemically enhanced primary treatment that was suggested to be governed by chemical-forced sedimentation. Distribution coefficient (Kd) of TCS was directly correlated to the total organic carbon of the sludge (TOC). Moreover, strong correlation was observed between elimination efficiency in primary sedimentation and loading concentration.

GC/MS analysis of triclosan and its degradation by-products in wastewater and sludge samples from different treatments.

A gas chromatography/mass spectrometry (GC/MS)-based method was developed for simultaneous determination of triclosan (TCS) and its degradation products including 2,4-dichlorophenol (2,4-DCP), 2,8-dichlorodibenzo-p-dioxin (2,8-DCDD), and methyl triclosan (MTCS) in wastewater and sludge samples. The method provides satisfactory detection limit, accuracy, precision and recovery especially for samples with complicated matrix such as sewage sludge. Liquid-liquid extraction and accelerated solvent extraction (ASE) methods were applied for the extraction, and column chromatography was employed for the sample cleanup. Analysis was performed by GC/MS in the selected ion monitoring (SIM) mode. The method was successfully applied to wastewater and sludge samples from three different municipal wastewater treatment plants (WWTPs). Satisfactory mean recoveries were obtained as 91(±4)-106(±7)%, 82(±3)-87(±4)%, 86(±6)-87(±8)%, and 88(±4)-105(±3)% in wastewater and 88(±5)-96(±8)%, 84(±2)-87(±3)%, 84(±7)-89(±4)%, and 88(±3)-97(±5)% in sludge samples for TCS, 2,4-DCP, 2,8-DCDD, and MTCS, respectively. TCS degradation products were detected based on the type of the wastewater and sludge treatment. 2,8-DCDD was detected in the plant utilizing UV disinfection at the mean level of 20.3(±4.8) ng/L. 2,4-DCP was identified in chemically enhanced primary treatment (CEPT) applying chlorine disinfection at the mean level of 16.8(±4.5) ng/L). Besides, methyl triclosan (MTCS) was detected in the wastewater collected after biological treatment (10.7 ± 3.3 ng/L) as well as in sludge samples that have undergone aerobic digestion at the mean level of 129.3(±17.2) ng/g dry weight (dw).