Therapeutic approach for global myocardial injury using bone marrow-derived mesenchymal stem cells by cardiac support device in rats.

Bone marrow-derived mesenchymal stem cells (BMSCs) have been considered a promising therapeutic approach to cardiovascular disease. This study intends to compare the effect of BMSCs through a standard active cardiac support device (ASD) and intravenous injection on global myocardial injury induced by isoproterenol. BMSCs were cultured in vitro, and the transplanted cells were labeled with a fluorescent dye CM-Dil. Isoproterenol (ISO) was injected into the rats; 2 weeks later, the labeled cells were transplanted into ISO-induced heart-jury rats through the tail vein or ASD device for 5 days. The rats were sacrificed on the first day, the third day, and the fifth day after transplantation to observe the distribution of cells in the myocardium by fluorescence microscopy. The hemodynamic indexes of the left ventricle were measured before sacrificing. H&E staining and Masson's trichrome staining were used to evaluate the cardiac histopathology. In the ASD groups, after 3 days of transplantation, there were a large number of BMSCs on the epicardial surface, and after 5 days of transplantation, BMSCs were widely distributed in the ventricular muscle. But in the intravenous injection group, there were no labeled-BMSCs distributed. In the ASD + BMSCs-three days treated group and ASD + BMSCs -five days-treated group, left ventricular systolic pressure (LVSP), the maximum rate of left ventricular pressure rise (+dP/dt), the maximum rate of left ventricular pressure decline (-dP/dt) increased compared with model group and intravenous injection group (P < 0.05). By giving BMSCs through ASD device, cells can rapidly and widely distribute in the myocardium and significantly improve heart function.

Factors influencing treatment outcomes of tuberculosis patients attending health facilities in Galkayo Puntland, Somalia.

AIM: This study evaluated the underlying factors associated with poor tuberculosis (TB) treatment outcomes among patients attending health care facilities in Galkayo, Puntland, Somalia. METHODS: An institution-based cross-sectional study was conducted between 2016 and 2017 in three selected TB clinics. Data were collected from 400 TB patients, through medical record review and structured questionnaire. Multivariate logistic regression analyses were performed. RESULTS: Of the 400 TB respondents, 57.3% were new cases, 12.3% had smear-negative TB and 12.5% had extrapulmonary TB. The median age was (35.66 ± 13.16) with majority being male (65.5%). Overall, 85% of patients were successfully treated, 9.7% failed and 5.3% defaulted. Multivariate analysis revealed that patient's body weight (odds ratio [OR]: 1.078); diabetes (OR: 8.022); family size (OR: 3.851); patients' delay in diagnosis (OR: 11.946); frequency of receiving anti-TB medication (OR: 9.068); smoker (OR: 5.723); category of patients (retreatment versus new, OR: 5.504; retreatment versus transfer in, OR: 4.957); health facilities (OR: 6.716) and treatment duration (OR: 132.091) were independent factors associated with poor TB outcomes. CONCLUSIONS: Our findings highlight the need to improve TB services for vulnerable groups. They also emphasize the need for health system strengthening, public awareness and risk of treatment interruption. This may reduce both patients' delay in seeking care and TB treatment failure in Galkayo district.

Chemical characterization and anti-arthritic appraisal of Monotheca buxifolia methanolic extract in Complete Freund's Adjuvant-induced arthritis in Wistar rats.

The current study was designed to evaluate the anti-oxidant and anti-arthritic potential of a traditionally used herb, Monotheca buxifolia. The M. buxifolia methanolic extract (MBME) was prepared from the aerial parts of the plant followed by chemical characterization with GC-MS. The anti-oxidant potential of the MBME was demonstrated by DPPH scavenging activity. The effects of MBME on protein denaturation and membrane stabilization were determined by inhibition of egg albumin denaturation and RBC membrane stabilization assays, respectively. The in vivo anti-arthritic potential of the MBME at 50, 100, and 150 mg/kg/day was evaluated in Complete Freund's Adjuvant-induced polyarthritis in Wistar rats treated for 21 days. Phytochemicals, such as linolenic acid methyl ester, n-hexadecanoic acid, vitamin E, α-amyrin, and ß-amyrin were detected in the GC-MS analysis. The plant extract exhibited a 55.20 ± 0.69% scavenging of free radicals at 100 µg/ml concentration. It significantly (p < 0.05) stabilized human RBC membrane (65.06 ± 0.22%) and inhibited protein denaturation (70.53 ± 0.34%) at 100 mg/ml concentration. The diclofenac sodium (DS) and MBME at 150,100, and 50 mg/kg reduced the paw edema, restored the body weight, and altered blood parameters including CRP. The MBME significantly reduced the MDA and increased the SOD, CAT, and GSH levels in liver tissue homogenate in treated rats. The serum concentration of TNF-α and PGE2 was remarkably (p < 0.01-< 0.0001) restored by the DS and MBME dose dependently. The histopathological study showed that MBME 150 mg/kg commendably restored the ankle joint inflammation, bone erosion, and cartilage damage in polyarthritic rats. It was concluded that the anti-oxidant, anti-inflammatory and anti-arthritic effects of MBME might be attributed to phenols, flavonoids, triterpenoids, vitamin E, phytol, and other fatty acids. This study showed the anti-arthritic potential of Monotheca buxifolia and thus validates its traditional claim.

Mass Transfer Modulation and Gas Mapping Based on Covalent Organic Frameworks-Covered Theta Micropipette.

Covalent organic frameworks (COFs) consist nanochannels that are fundamentally important for their application. Up to now, the effect of gas phase on COF nanochannels are hard to explore. Here, TAPB-PDA-COFs (triphenylbenzene-terephthaldehyde-COFs) was synthesized in situ at the tip of a theta micropipette. The COF-covered theta micropipette (CTP) create a stable gas-liquid interface inside the COF nanochannels, through which the humidity-modulated ion mass transfer in the COF nanochannels can be recorded by recording the current across the two channels of the theta micropipette. Results show that the humid air changes the mobility of the ions inside the COF nanochannels, which leads to the change of ionic current. Humid air showed different effects on the ion transfer depending on the solvent polarity index and vapor pressure. Current decreases linearly with the increase of relative humidity (RH) from 11% to 98%. The CTP was also mounted on the scanning electrochemical microscopy as a probe electrode for mapping micrometer-scale humidity distribution.

Pharmacokinetic Advantage of ASD Device Promote Drug Absorption through the Epicardium.

PURPOSE: Due to low therapeutic efficacy and severe adverse reaction of systemic administration for coronary heart disease (CHD) therapy, we designed a novel local target delivery system, called Active hydraulic ventricular Support Drug delivery system (ASD). This study aims to investigate the potential advantages of ASD compared to intrapericardial (IPC) injection and factors affecting drug absorption through epicardium. METHODS: Liposoluble, water soluble and viscous solutions of cyanine 5 (Cy5) fluorescent dye were delivered individually through ASD and IPC in Sprague-Dawley (SD) rats and then tissues were isolated and observed by in vivo imaging system. Atria and ventricles of the heart were taken for the paraffin section and observed under a fluorescence microscope. RESULTS: The fluorescence intensity of Cy5 injected by ASD distributed in the heart was significantly higher than IPC injection. Whereas, the fluorescence signal spread in other tissues such as lung, liver, spleen, and kidney of ASD groups was much weaker. Moreover, when choosing liposoluble and viscous Cy5, the intensity of the heart turned stronger and fluorescence dye distributed in other tissues was lesser. CONCLUSIONS: The application of ASD device may provide a promising route of drug delivery for CHD. Furthermore, increasing viscosity of the solution and liposolublity of the drug was beneficial to facilitate drug absorption through the epicardium.

Synthesis of Ligand Functionalized ErbB-3 Targeted Novel DNA Nano-Threads Loaded with the Low Dose of Doxorubicin for Efficient In Vitro Evaluation of the Resistant Anti-Cancer Activity.

PURPOSE: Doxorubicin (Dox) being a hydrophobic drug needs a unique carrier for the effective encapsulation with uniformity in the aqueous dispersion, cell culture media and the biological-fluids that may efficiently target its release at the tumor site. METHODS: Circular DNA-nanotechnology was employed to synthesize DNA Nano-threads (DNA-NTs) by polymerization of triangular DNA-tiles. It involved circularizing a linear single-stranded scaffold strand to make sturdier and rigid triangles. DNA-NTs were characterized by the AFM and Native-PAGE tests. Dox binding and loading to the Neuregulin1 (NRG1) functionalized DNA based nano-threads (NF-DBNs) was estimated by the UV-shift analysis. The biocompatibility of the blank NRG-1/DNA-NTs and enhanced cytotoxicity of the NF-DBNs was assessed by the MTT assay. Cell proliferation/apoptosis was analyzed through the Flow-cytometry experiment. Cell-surface binding and the cell-internalization of the NF-DBNs was captured by the double-photon confocal microscopy (DPCM). RESULTS: The AFM images revealed uniform DNA-NTs with the diameter 30 to 80 nm and length 400 to 800 nm. PAGE native gel was used for the further confirmation of the successful assembly of the strands to synthesize DNA-NTs that gave one sharp band with the decreased electrophoretic mobility down the gel. MTT assay showed that blank DNA-NTs were biocompatible to the cells with less cytotoxicity even at elevated concentrations with most of the cells (94%) remaining alive compared to the dose-dependent enhanced cytotoxicity of NF-DBNs further evidenced by the Flow-cytometry analysis. CONCLUSION: Uniform and stiffer DNA-NTs for the potential applications in targeted drug delivery was achieved through circular DNA scaffolding.

A DNA Nanodevice Simultaneously Activating the EGFR and Integrin for Enhancing Cytoskeletal Activity and Cancer Cell Treatment.

Cell-surface receptors (e.g., EGFR and integrin) and their interactions play determining roles in signal transduction and cytoskeletal activation, which affect cell attachment/detachment, invasion, motility, metastasis (intracellular), and cell-cell signaling. For instance, the interactions between the EGFR and integrin (α6ß4) may cause increased mechanical force and shear stress via enhanced cytoskeleton activation. Here, we design a DNA nanodevice (DNA-ND) that can simultaneously target the EGFR and integrin receptors on the caveolae. The piconewton (pN) forces in response to the EGFR-integrin coactivation can be sensed upon the unfolding of the DNA hairpin structure on the side arm of the device via changes of the fluorescence and plasmonic signals. We find that simultaneous activation of EGFR-integrin receptors causes enhanced signal transduction, contractions of the cells, and initiation of the biochemical pathways, thus resulting in a change of the cell division and endocytosis/exocytosis processes that affect the cell proliferation/apoptosis. The DNA-ND further enables us to visualize the cointernalization and degradation of the receptors by lysosomes, providing a novel approach toward bioimaging and mechano-pharmacology.

Mitochondria-dependent apoptosis in triptolide-induced hepatotoxicity is associated with the Drp1 activation.

How triptolide is associated with mitochondrial dysfunction and apoptosis in connection with its hepatotoxicity remains unclear. The objective of our study was to find out the link between mitochondrial dynamics and cell death in triptolide induced hepatotoxicity. We treated L02 cells with 25 nM concentration of triptolide. The results demonstrated that triptolide treatment caused an increase in apoptotic cell death, mitochondrial depolarization, ROS overproduction, a decrease in ATP production, and mitochondrial fragmentation which in turn is associated with the activation of Drp1 fission protein. Triptolide treatment led to the translocation of Drp1 from the cytosol into outer mitochondrial membrane where it started mitochondrial fission. This fission event is coupled with the mitochondrial release of cytochrome c into the cytosol and subsequently caspase-3 activation. TEM analysis of rat liver tissues revealed the distortion of mitochondrial morphology in triptolide-treated group. Western blot analysis explained that disruption in mitochondrial morphology was attached with the recruitment of Drp1 to mitochondria, cytochrome c release, and caspase-3 activation. However, Mdivi-1 co-treatment inhibited the activation of Drp1 and caspase-3 and blocked the release of cytochrome c into the cytosol. In short, inhibiting Drp1 protein activation may provide a new potential target for curing Drp1-associated apoptosis in triptolide-induced hepatotoxicity.

Development of mRNA nano-vaccines for COVID-19 prevention and its biochemical interactions with various disease conditions and age groups.

This review has focused on the development of mRNA nano-vaccine and the biochemical interactions of anti-COVID-19 mRNA vaccines with various disease conditions and age groups. It studied five major groups of individuals with different disease conditions and ages, including allergic background, infarction background, adolescent, and adult (youngsters), pregnant women, and elderly. All five groups had been reported to have background-related adverse effects. Allergic background individuals were observed to have higher chances of experiencing allergic reactions and even anaphylaxis. Individuals with an infarction background had a higher risk of vaccine-induced diseases, e.g. pneumonitis and interstitial lung diseases. Pregnant women were seen to suffer from obstetric and gynecological adverse effects after receiving vaccinations. However, interestingly, the elderly individuals (> 65 years old) had experienced milder and less frequent adverse effects compared to the adolescent (<19 and >9 years old) and young adulthood (19-39 years old), or middle adulthood (40-59 years old) age groups, while middle to late adolescent (14-17 years old) was the riskiest age group to vaccine-induced cardiovascular manifestations.

Development of biomedical hydrogels for rheumatoid arthritis treatment.

Rheumatoid Arthritis (RA) is an autoimmune disorder that hinders the normal functioning of bones and joints and reduces the quality of human life. Every year, millions of people are diagnosed with RA worldwide, particularly among elderly individuals and women. Therefore, there is a global need to develop new biomaterials, medicines and therapeutic methods for treating RA. This will improve the Healthcare Access and Quality Index and also relieve administrative and financial burdens on healthcare service providers at a global scale. Hydrogels are soft and cross-linked polymeric materials that can store a chunk of fluids, drugs and biomolecules for hydration and therapeutic applications. Hydrogels are biocompatible and exhibit excellent mechanical properties, such as providing elastic cushions to articulating joints by mimicking the natural synovial fluid. Hence, hydrogels create a natural biological environment within the synovial cavity to reduce autoimmune reactions and friction. Hydrogels also lubricate the articulating joint surfaces to prevent degradation of synovial surfaces of bones and cartilage, thus exhibiting high potential for treating RA. This work reviews the progress in injectable and implantable hydrogels, synthesis methods, types of drugs, advantages and challenges. Additionally, it discusses the role of hydrogels in targeted drug delivery, mechanistic behaviour and tribological performance for RA treatment.

A combination of gliclazide and metformin attenuates obesity-induced polycystic ovary syndrome in female Wistar rats.

Presently, it is known that the progression of obesity concomitantly leads to polycystic ovary syndrome and infertility. This study aimed to evaluate the potential effects of metformin (M; insulin secretagogues) and gliclazide (G; insulin sensitizer) alone and their combination at different doses to treat obesity-induced PCOS. High high-fat diet was given to all female Wistar rats for nine weeks to induce obesity except for the normal control group which received a normal chow diet. Estradiol valerate (0.8 mg/kg) was also given to all obese rats to induce polycystic ovarian syndrome. After the induction, M (100, 300 mg/kg) and G (5, 10 mg/kg) were given orally either individually or in combination for 28 days. The notable (p < 0.0001) reduction in body weight and blood glucose level was observed in treatment groups in contrast to disease control (DCG). The marked (p < 0.05-0.0001) decrease in hemocylated hemoglobin, serum insulin, cholesterol, triglycerides, and testosterone was observed in treated groups, notably in combination groups (M100+G10 mg/kg) in contrast to DCG. There was a considerable (p < 0.01-0.0001) increase in progesterone E2, estradiol, luteinizing, and follicle-stimulating hormones in treated groups as compared to DCG. Treatment with M and G treated groups also exhibited marked (p < 0.05-0.0001) increases in SOD, CAT, and GSH while decreased in NO and MDA levels in ovary tissue as evidenced by the histological study of the ovary. Treatment with M and G alone and in combination significantly (p < 0.0001) restored the serum IL-6, NrF2, and NF-κB levels as compared to DCG. The results inveterate that the M and G combination (M100+G10, and M300+G10) was useful in treating obesity-induced infertility due to antioxidant properties, hypolipidemic effects, and modulation of inflammatory markers.

Current Updates on the Role of MicroRNA in the Diagnosis and Treatment of Neurodegenerative Diseases.

BACKGROUND: MicroRNAs (miRNA) are small noncoding RNAs that play a significant role in the regulation of gene expression. The literature has explored the key involvement of miRNAs in the diagnosis, prognosis, and treatment of various neurodegenerative diseases (NDD), such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). The miRNA regulates various signalling pathways; its dysregulation is involved in the pathogenesis of NDD. OBJECTIVE: The present review is focused on the involvement of miRNAs in the pathogenesis of NDD and their role in the treatment or management of NDD. The literature provides comprehensive and cutting-edge knowledge for students studying neurology, researchers, clinical psychologists, practitioners, pathologists, and drug development agencies to comprehend the role of miRNAs in the NDD's pathogenesis, regulation of various genes/signalling pathways, such as α-synuclein, P53, amyloid-ß, high mobility group protein (HMGB1), and IL-1ß, NMDA receptor signalling, cholinergic signalling, etc. Methods: The issues associated with using anti-miRNA therapy are also summarized in this review. The data for this literature were extracted and summarized using various search engines, such as Google Scholar, Pubmed, Scopus, and NCBI using different terms, such as NDD, PD, AD, HD, nanoformulations of mRNA, and role of miRNA in diagnosis and treatment. RESULTS: The miRNAs control various biological actions, such as neuronal differentiation, synaptic plasticity, cytoprotection, neuroinflammation, oxidative stress, apoptosis and chaperone-mediated autophagy, and neurite growth in the central nervous system and diagnosis. Various miRNAs are involved in the regulation of protein aggregation in PD and modulating ß-secretase activity in AD. In HD, mutation in the huntingtin (Htt) protein interferes with Ago1 and Ago2, thus affecting the miRNA biogenesis. Currently, many anti-sense technologies are in the research phase for either inhibiting or promoting the activity of miRNA. CONCLUSION: This review provides new therapeutic approaches and novel biomarkers for the diagnosis and prognosis of NDDs by using miRNA.

Micro- and nanoplastics: Contamination routes of food products and critical interpretation of detection strategies.

Micro-and nanoplastics (M/NPs) are emerging pollutants released into the food, beverages, and environment from plastic products by weathering, oxidative damage, and mechanical stress. Detection of M/NPs in food and beverages is a vital factor in preventing the deleterious effects of these materials on human health and other ecosystems. Analytical strategies for M/NPs demonstrate numerous drawbacks, including detection sensitivity limitation, matrix digestion, and sample pretreatment. Moreover, the content of M/NPs in food and beverages varies with food production, storage, and transport, making it hard to precisely detect them. The contamination route is a key factor affecting the level of M/NPs in food and beverages. Strict control over the contamination route could be beneficial in preventing M/NP pollution. This review highlighted routes of food and beverage contamination by M/NPs, various pros and cons of detection strategies, and critical interpretation of reported techniques, including microscopy, spectroscopy, light scattering, and thermal methods. Besides, the bottlenecks of detection and quantification approaches for M/NPs and recent advancements have also been highlighted. Much is still unknown concerning the fate, activities, and properties of M/NPs present in various matrices. This review aims to assist the investigators to tackle the drawbacks and pave the way for upcoming research, minimizing the health complications by regulating the control over M/NPs pollution.

Exploring the robustness of DNA nanotubes framework for anticancer theranostics toward the 2D/3D clusters of hypopharyngeal respiratory tumor cells.

This study aimed to develop a robust approach for the early diagnosis and treatment of tumors. Short circular DNA nanotechnology synthesized a stiff and compact DNA nanotubes (DNA-NTs) framework. TW-37, a small molecular drug, was loaded into DNA-NTs for BH3-mimetic therapy to elevate the intracellular cytochrome-c levels in 2D/3D hypopharyngeal tumor (FaDu) cell clusters. After anti-EGFR functionalization, the DNA-NTs were tethered with a cytochrome-c binding aptamer, which can be applied to evaluate the elevated intracellular cytochrome-c levels via in situ hybridization (FISH) analysis and fluorescence resonance energy transfer (FRET). The results showed that DNA-NTs were enriched within the tumor cells via anti-EGFR targeting with a pH-responsive controlled release of TW-37. In this way, it initiated the triple inhibition of "BH3, Bcl-2, Bcl-xL, and Mcl-1". The triple inhibition of these proteins caused Bax/Bak oligomerization, leading to the perforation of the mitochondrial membrane. This led to the elevation of intracellular cytochrome-c levels, which reacted with the cytochrome-c binding aptamer to produce FRET signals. In this way, we successfully targeted 2D/3D clusters of FaDu tumor cells and achieved the tumor-specific and pH-triggered release of TW-37, causing tumor cell apoptosis. This pilot study suggests that anti-EGFR functionalized, TW-37 loaded, and cytochrome-c binding aptamer tethered DNA-NTs might be the hallmark for early tumor diagnosis and therapy.

Corrigendum to "The effective transfection of a low dose of negatively charged drug-loaded DNA-nanocarriers into cancer cells via scavenger receptors"[Journal of Pharmaceutical Analysis volume 11 (2021) 174-182].

[This corrects the article DOI: 10.1016/j.jpha.2020.10.003.].

Nanoscale packing of DNA tiles into DNA macromolecular lattices.

Nanoscale double-crossovers (DX), antiparallel (A), and even half-turns-perimeter (E) DNA tiles (DAE-tiles) with rectangular shapes can be packed into large arrays of micrometer-scale lattices. But the features and mechanical strength of DNA assembly made from differently shaped large-sized DAE DNA tiles and the effects of various geometries on the final DNA assembly are yet to be explored. Herein, we focused on examining DNA lattices synthesized from DX bi-triangular, DNA tiles (T) with concave and convex regions along the perimeter of the tiles. The bi-triangular DNA tiles "T(A) and T(B)" were synthesized by self-assembling the freshly prepared short circular scaffold (S) strands "S(A) and S(B)", each of 106 nucleotides (NT) lengths. The tiles "T(A) and T(B)" were then coupled together to get assembled via sticky ends. It resulted in the polymerization of DNA tiles into large-sized DNA lattices with giant micrometer-scale dimensions to form the "T(A) + T(B)" assembly. These DNA macro-frameworks were visualized "in the air" under atomic force microscopy (AFM) employing tapping mode. We have characterized how curvature in DNA tiles may undergo transitions and transformations to adjust the overall torque, strain, twists, and the topology of the final self-assembly array of DNA tiles. According to our results, our large-span DX tiles assembly "T(A) + T(B)" despite the complicated curvatures and mechanics, was successfully packed into giant DNA lattices of the width of 30-500 nm and lengths of 500 nm to over 10 µm. Conclusively, the micrometer-scale "T(A) + T(B)" framework assembly was rigid, stable, stiff, and exhibited enough tensile strength to form monocrystalline lattices.

Disrupting biofilm and eradicating bacteria by Ag-Fe3O4@MoS2 MNPs nanocomposite carrying enzyme and antibiotics.

In this study, novel multilayered magnetic nanoparticles (ML-MNPs) loaded with DNase and/or vancomycin (Vanc) were fabricated for eliminating multispecies biofilms. Iron-oxide MNPs (IO-core) (500-800 nm) were synthesized via co-precipitation; further, the IO-core was coated with heavy-metal-based layers (Ag and MoS2 NPs) using solvent evaporation. DNase and Vanc were loaded onto the outermost layer of the ML-MNP formed by nanoporous MoS2 NPs through physical deposition and adsorption. The biofilms of S. mutans or E. faecalis (or both) were formed in a brain-heart-infusion broth (BHI) for 3 days, followed by treatment with ML-MNPs for 24 h. The results revealed that coatings of Ag (200 nm) and ultrasmall MoS2 (20 nm) were assembled as outer layers of ML-MNPs successfully, and they formed Ag-Fe3O4@MoS2 MNPs (3-5 µm). The DNase-Vanc-loaded MNPs caused nanochannels digging and resulted in the enhanced penetration of MNPs towards the bottom layers of biofilm, which resulted in a decrease in the thickness of the 72-h biofilm from 48 to 58 µm to 0-4 µm. The sustained release of Vanc caused a synergistic bacterial killing up to 96%-100%. The heavy-metal-based layers of MNPs act as nanozymes to interfere with bacterial metabolism and proliferation, which adversely affects biofilm integrity. Further, loading DNase/Vanc onto the nanoporous-MoS2-layer of ML-MNPs promoted nanochannel creation through the biofilm. Therefore, DNase-and Vanc-loaded ML-MNPs exhibited potent effects on biofilm disruption and bacterial killing.

Hepatoprotective effect of Cordia rothii extract against CCl4-induced oxidative stress via Nrf2-NFκB pathways.

Cordia rothii Roem. & Schult. possesses various beneficial effects and is traditionally used in folk medicine against liver diseases but its molecular mechanism remains unclear. Antioxidant and hepatoprotective effects of Cordia rothii methanolic fraction (CRMF) were investigated in CCl4-induced liver injury. Antioxidant effects were evaluated using DPPH assay, ferric thiocyanate (FTC) assay, and HepG2 cells. A qualitative analysis of phytochemicals was carried out by gas chromatography-mass spectrometry (GC-MS). The hepatoprotective effects of CRMF were assessed against CCl4-induced liver damage in rats. Our results showed that CRMF significantly increased cell viability against CCl4-induced HepG2 cells. The in vivo results showed that CRMF significantly reduced the level of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, hepatic antioxidant enzymes, including superoxide dismutase, malondialdehyde, and increased glutathione level. Normal hepatocyte integrity and microstructures were observed in histopathological results. Furthermore, the mRNA level of inflammatory mediators including interleukon (IL)-1ß, IL-6, TNF-α, nuclear factor kappa B (NF-KB), IL-10 and nuclear factor-erythroid factor 2-related factor 2 (NrF2) were reverted in CRMF pretreatment groups. Thus, CRMF exhibited strong antioxidant, and hepatoprotective activities, which may involve Nrf2-NFκB pathways.

Drinking-water nitrate and cancer risk: A systematic review and meta-analysis.

BACKGROUND: Nitrate is an inorganic compound that occurs naturally in all surface and groundwater, although higher concentrations tend to occur only where fertilizers are used on the land. The regulatory limit for nitrate in public drinking water supplies was set to protect against infant methemoglobinemia, but other health effects were not considered. Risk of specific cancers and congenital disabilities may be increased when the nitrate is ingested, and nitrate is reduced to nitrite, which can react with amines and amides by nitrosation to form N-nitroso compounds which are known animal carcinogens. This study aims to evaluate the association between nitrate ingested through drinking water and the risk of developing cancers in humans. METHODS: We performed a systematic review following PRISMA and MOOSE guidelines. A literature search was performed using PubMed, EMBASE, the Cochrane Library databases, Web of Science and Google Scholars in the time-frame from their inception to January 2020, for potentially eligible publications. STATA version 12.0 was used to conduct meta-regression and a two-stage meta-analysis. RESULTS: A total of 48 articles with 13 different cancer sites were used for analysis. The meta-regression analysis showed stomach cancer had an association with the median dosage of nitrate from drinking water (t = 3.98, p = 0.0001, and adjusted R-squared = 50.61%), other types of cancers didn't show any association. The first stage of meta-analysis showed there was an association only between the risk of brain cancer & glioma (OR = 1.15, 95% CI: 1.06, 1.24) and colon cancer (OR = 1.11, 95% CI: 1.04, 1.17) and nitrate consumption in the analysis comparing the highest ORs versus the lowest. The 2nd stage showed there was an association only between the risk colon cancer (OR = 1.14, 95% CI: 1.04, 1.23) and nitrate consumption in the analysis comparing all combined higher ORs versus the lowest. CONCLUSION: This study showed that there is an association between the intake of nitrate from drinking water and a type of cancer in humans. The effective way of controlling nitrate concentrations in drinking water is the prevention of contamination (water pollution). Further research work on this topic is needed.