Oncogenic microRNA-1290 and SCAI Gene as Potential Biomarker for Colorectal Carcinoma.

INTRODUCTION: Colorectal cancer (CRC) is the world's third most frequent cancer, with a significant mortality rate due to late detection. There is a need to search for biomarkers that can detect colorectal cancer at an early stage. MicroRNAs (miRNAs) regulate several targets that function as oncogenes and/or tumor suppressor genes, so any change in microRNA expression level can predict abnormality. OBJECTIVE: The objective of the study was to evaluate the expression of miR-1290, and Suppressor of cancer cell invasion (SCAI) gene that may be used as biomarkers for early diagnosis of colorectal carcinoma. METHODOLOGY: This study included 50 subjects consisting of newly diagnosed colorectal carcinoma patients (n = 25), and healthy controls (n = 25). After RNA isolation and reverse transcription, the expression level of miR-1290 and SCAI gene in the tissues and plasma samples of CRC patients were analyzed using real time PCR and compared with healthy individuals as normal controls. The 2-ΔΔCt formula was used to compute the fold-change, while using miR-16 and GAPDH as reference genes for normalization. RESULTS: We found that miR-1290 is upregulated, whereas SCAI gene is downregulated in both plasma and tissue samples of CRC patients. For miR-1290, the sensitivity was 96% and specificity was 100%, and for SCAI, 100% sensitivity and 88% specificity was calculated by ROC analysis. CONCLUSION: The expression of miR-1290 and SCAI gene may be utilized as biomarkers for diagnosis of colorectal carcinoma.

Multivariate characterization of salicylic acid and potassium induced physio-biochemical and phytoremediation responses in quinoa exposed to lead and cadmium contamination.

The levels of soils pollutants such as lead (Pb) and cadmium (Cd) have significantly increased recently resulting in ecological disturbances and threatening crop production. Various amendments have been employed to enhance the tolerance of crops to withstand Cd and Pb stresses. However, the role of combined application of potassium (K) and of salicylic acid (SA) for Cd and Pb stress mitigation and phytoremediation by quinoa (Chenopodium quinoa Willd) has not been comprehended well. In the present study, the effect of 10 mM K and 0.1 mM SA was tested on the quinoa plants subjected to 250 µM Pb and/or 100 µM Cd. The Pb and Cd treatments were applied separately or together. Phytotoxicity induced by Pb and Cd resulted in drastic decrease (>60%) in chlorophyll contents, stomatal conductance, and plant biomass. The collective treatment of Pb and Cd induced an increase in the concentration of hydrogen peroxide (13-fold) and lipid peroxidation (16-fold) that resulted in a 61% reduction in membrane stability. The application of 10 mM K and/or 0.1 mM SA was remarkable in mitigating the adverse effect of Pb and Cd. The reduction in plant biomass was 17% when 10 mM K and 0.1 mM SA were applied together under the combined treatment of both the metals. The simultaneous application of K and SA effectively mitigated oxidative stress by enhancing the activities of superoxide dismutase, peroxidase, ascorbate peroxidase, and catalase by 12, 10, 7 and 10-folds respectively. The positive effect of K and SA on these attributes resulted in a remarkable reduction in metal accumulation and translocation and lipid peroxidation. The stressed plants supplemented with K and SA exhibited a significant improvement in the membrane stability index, chlorophyll content, and stomatal conductance. This study concluded that the combined application of K and SA could be a good approach for reducing Pb and Cd phytotoxicity in quinoa and enhancing their phytostabilization potential in the contaminated soils.

Occurrence of fungal microbial contamination in drinking water of megacity of Karachi (Pakistan) and their physico-chemical control.

The water quality in Karachi (Pakistan) is uncertain due to the occurrence of fungi and other microorganisms. A total of twenty-five water samples were collected from public places, educational institutes, hospitals, water supply systems and surface water of the canal of Karachi (Pakistan). The different fungal species including Acremonium sp., Alternaria alternata, Aspergillus flavus, A. fumigatus, A. sulphureus, Cladosporium sp., Fusarium sp., Clonostachys (Gliocladium) sp., Macrophomina phaseolina, Mucor racemosus, Paecilomyces sp. Penicillium chrysogenum, P. citrinum, P. commune, P. expansum, Rhizoctonia sp. and Stachybotrys sp. were isolated from these drinking water samples. However, the bacteria, microalgae and some other microorganisms were present in low concentrations. The reason for fungi infection and production of mycotoxicity depends upon various factors and the availability of their nutrients in filtration plants. The major threats to human health are fungal mycotoxicity which is responsible for carcinogenic and other lethal diseases. Mostly, the genus Aspergillus was dominated and isolated with a maximum of 88-98% of occurrence in the different samples of drinking water by the direct plate-spread method. For the control of fungi, various Physico-chemical coagulation treatments were used, but Potassium alum, clay pot, and hot water treatment disinfected effectively 69-70% removal of the fungi and its spore or mycelia from the water. In addition, it is concluded that drinking water purifications such as chlorination, filtration and lime did not eliminate thermophilic fungal spores or mycelia including Penicillium, Paecilomyces and Mucor from the water.

Salicylic Acid- and Potassium-Enhanced Resilience of Quinoa (Chenopodium quinoa Willd.) against Salinity and Cadmium Stress through Mitigating Ionic and Oxidative Stress.

Salinity and cadmium (Cd) contamination of soil are serious environmental issues threatening food security. This study investigated the role of salicylic acid (SA) and potassium (K) in enhancing the resilience of quinoa against the combined stress of salinity and Cd. Quinoa plants were grown under NaCl (0, 200 mM) and Cd (0, 100 µM) stress, with the addition of 0.1 mM SA and 10 mM K, separately or in combination. The joint stress of Cd and NaCl caused >50% decrease in plant growth, chlorophyll contents, and stomatal conductance compared to the control plants. The higher accumulation of Na and Cd reduced the uptake of K in quinoa tissues. The joint stress of salinity and Cd caused an 11-fold increase in hydrogen peroxide and 13-fold increase in thiobarbituric acid reactive substances contents, and caused a 61% decrease in membrane stability. An external supply of 0.1 mM SA and 10 mM K helped plants to better adapt to salinity and Cd stress with less of a reduction in plant biomass (shoot 19% and root 24%) and less accumulation of Na and Cd in plant tissues. The activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) were enhanced by 11-fold, 10-fold, 7.7-fold, and 7-fold, respectively, when SA and K were applied together to the plants subjected to the joint stress of Cd and salinity. Based on the values of the bioconcentration factor (>1), the translocation factor (<1), and the higher tolerance index, it was clear that Cd-contaminated, salty soils could be stabilized with quinoa under the combined supply of SA and K.

The mutational analysis of mitochondrial DNA in maternal inheritance of polycystic ovarian syndrome.

Introduction: Polycystic Ovarian Syndrome (PCOS) is a globally prevalent condition that leads to infertility in women. While environmental factors contribute to PCOS, maternal genetics also play a significant role. Currently, there is no definitive test for identifying predisposition to PCOS. Hence, our objective is to discover novel maternal genetic risk factors for PCOS by investigating the genomes of patients from Pakistan. Methods: We utilized Next-Generation Sequencing (NGS) to sequence the complete mitochondrial DNA of three PCOS patients. Subsequently, we employed MitoTIP (Mitochondrial tRNA Informatics Predictor) and PON-mt-tRNA tools to identify variations in the mitochondrial DNA. Our analysis focused on the genes MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB, which displayed common variations in all three genomes. Additionally, we observed individual variations. The D-loop region exhibited the highest frequency of mutations, followed by the non-coding regions of RNR1 and RNR2 genes. Moreover, we detected frameshift mutations in the mitochondrially encoded NADH Dehydrogenase 2 (MT-ND2) and mitochondrially encoded NADH Dehydrogenase 5 (ND5) genes within individual genomes. Results: Our analysis unveiled six regions with common variations in the mitochondrial DNA of all three PCOS patients. Notably, the MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB genes exhibited these variations. Additionally, we identified individual variations in the mitochondrial DNA. The D-loop region displayed the highest mutation frequency, followed by the non-coding regions of RNR1 and RNR2 genes. Furthermore, frameshift mutations were detected in the MT-ND2 and ND5 genes within individual genomes. Conclusion: Through our study, we have identified variations in mitochondrial DNA that may be associated with the development of PCOS and have the potential to serve as predisposition tests. Our findings highlight the presence of novel mutations in the MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB genes, as well as frameshift mutations in the MT-ND2 and ND5 genes. Pathogenicity analysis indicated that most variants were likely to result in benign cysts. However, the frameshift mutations in the ND2 gene were associated with a high risk of complications and pathogenicity in PCOS. This is the first report identifying these mutations and their association with PCOS, contributing to our understanding of the genetic factors underlying the condition.

Chitosan-coated halloysite nanotube magnetic microspheres for carcinogenic colorectal hemorrhage and liver laceration in albino rats.

Carcinogenic colorectal hemorrhage can cause severe blood loss and longitudinal ulcer, which ultimately become fatal if left untreated. The present study was aimed to formulate targeted release gemcitabine (GC)-containing magnetic microspheres (MM) of halloysite nanotubes (MHMG), chitosan (MCMG), and their combination (MHCMG). The preparation of MM by magnetism was confirmed by vibrating sample magnetometry (VSM), the molecular arrangement of NH2, alumina, and silica groups was studied by X-ray diffraction (XRD) and energy-dispersive spectroscopy (EDS), the hollow spherical nature of the proposed MM was observed by scanning electron microscopy (SEM), functional groups were characterized by Fourier transform infrared (FTIR) spectroscopy and thermochemical modification was studied by thermogravimetric analysis (TGA). In vitro thrombus formation showed a decreasing trend of hemostatic time for MMs in the order of MHMG3 < MCMG3 < MHCMG7, which was confirmed by whole blood clotting kinetics. Interestingly, rat tail amputation and liver laceration showed 3 folds increased clotting efficiency of optimized MHCMG7 compared to that of control. In vivo histopathological studies and cell viability assays confirmed the regeneration of epithelial cells. The negligible systemic toxicity of MHCMG7, more than 90% entrapment of GC and high % release in alkaline medium made the proposed MM an excellent candidate for the control of hemorrhage in colorectal cancer. Conclusively, the healing of muscularis and improved recovery of the colon from granulomas ultimately improved the therapeutic effects of GC-containing MMs. The combination of both HNT and CTS microspheres made them more targeted.

Modification of Cellulose Ether with Organic Carbonate for Enhanced Thermal and Rheological Properties: Characterization and Analysis.

Reduction in viscosity at higher temperatures is the main limitation of utilizing cellulose ethers in high thermal reservoir conditions for petroleum industry applications. In this study, cellulose ether (hydroxyethyl methyl cellulose (HEMC)) is modified using organic carbonates, i.e., propylene carbonate (PC) and diethyl carbonate (DEC), to overcome the limitation of reduced viscosity at high temperatures. The polymer composites were characterized through various analytical techniques, including Fourier-transform infrared (FTIR), H-NMR, X-ray diffraction (XRD), scanning electron microscope (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), ζ-potential measurement, molecular weight determination, and rheology measurements. The experimental results of structural and morphological characterization confirm the modification and formation of a new organic carbonate-based cellulose ether. The thermal analysis revealed that the modified composites have greater stability, as the modified samples demonstrated higher vaporization and decomposition temperatures. ζ-potential measurement indicates higher stability of DEC- and PC-modified composites. The relative viscometry measurement revealed that the modification increased the molecular weight of PC- and DEC-containing polymers, up to 93,000 and 99,000 g/moL, respectively. Moreover, the modified composites exhibited higher levels of stability, shear strength and thermal resistance as confirmed by viscosity measurement through rheology determination. The observed increase in viscosity is likely due to the enhanced inter- and intramolecular interaction and higher molecular weight of modified composites. The organic carbonate performed as a transesterification agent that improves the overall properties of cellulose ether (HEMC) at elevated temperatures as concluded from this study. The modification approach in this study will open the doors to new applications and will be beneficial for substantial development in the petroleum industry.

Diagnosis of nasopharyngeal carcinoma using an ultrasensitive immunoassay method based on nanoparticles.

The detection of the antibody of Epstein-Barr virus (EBV) is critical for the diagnosis of nasopharyngeal carcinoma (NPC). An accurate and scalable point-of-care detection method would support the screening, diagnosis, and monitoring of NPC patients. In this study, firstly, we made an antibody enrichment element, antigen-MNPs, which can screen out specific antibodies in a complex sample. Secondly, signal-amplifying elements were synthesized by labelling inorganic quantum dots (QDs) and anti-antibodies on the surface of flop-ferritin. A sandwich structure is formed among antigen-MNPs, target-antibodies, and anti-antibodies-flop-ferritin@QDs. The antibodies are quantified by fluorescence intensity with a limit of detection (LOD) as low as 10-11 g mL-1. Moreover, the method can detect different types of antibodies and was employed to examine 10 sera from NPC patients and 10 sera from healthy individuals. The result indicates that the simultaneous detection of anti-EBNA-IgG and anti-EBNA-IgA provides an efficient route for early diagnosis of NPC.

Construction of Genetically Encoded Biosensors to Monitor Subcellular Compartment-Specific Glutathione Response to Chemotherapeutic Drugs in Acute Myeloid Leukemia Cells.

Glutathione (GSH), the constituent of the redox buffer system, is a scavenger of reactive oxygen species (ROS), and its ratio to oxidized glutathione (GSSG) is a key indicator of oxidative stress in the cell. Acute myeloid leukemia (AML) is a highly aggressive hematopoietic malignancy characterized by aberrant levels of reduced and oxidized GSH due to oxidative stress. Therefore, the real-time, dynamic, and highly sensitive detection of GSH/GSSG in AML cells is of great interest for the clinical diagnosis and treatment of leukemia. The application of genetically encoded sensors to monitor GSH/GSSG levels in AML cells is not explored, and the underlying mechanism of how the drugs affect GSH/GSSG dynamics remains unclear. In this study, we developed subcellular compartment-specific sensors to monitor GSH/GSSG combined with high-resolution fluorescence microscopy that provides insights into basal GSH/GSSG levels in the cytosol, mitochondria, nucleus, and endoplasmic reticulum of AML cells, in a decreasing order, revealing substantial heterogeneity of GSH/GSSG level dynamics in different subcellular compartments. Further, we investigated the response of GSH/GSSG ratio in AML cells caused by Prussian blue and Fe3O4 nanoparticles, separately and in combination with cytarabine, pointing to steep gradients. Moreover, cytarabine and doxorubicin downregulated the GSH/GSSG levels in different subcellular compartments. Similarly, live-cell imaging showed a compartment-specific decrease in response to various drugs, such as CB-839, parthenolide (PTL), and piperlongumine (PLM). The enzymatic activity assay revealed the mechanism underlying fluctuations in GSH/GSSG levels in different subcellular compartments mediated by these drugs in the GSH metabolic pathway, suggesting some potential therapeutic targets in AML cells.

Salinity mitigates cadmium-induced phytotoxicity in quinoa (Chenopodium quinoa Willd.) by limiting the Cd uptake and improved responses to oxidative stress: implications for phytoremediation.

Cadmium (Cd) contamination and soil salinity are the main environmental issues reducing crop productivity. This study aimed to examine the combined effects of salinity (NaCl) and Cd on the physiological and biochemical attributes of quinoa (Chenopodium quinoa Willd.). For this purpose, 30-day-old plants of quinoa genotype "Puno" were transplanted in Hoagland's nutrient solution containing diverse concentrations of Cd: 0, 50, 100, 200 µM Cd, and salinity: 0, 150, and 300 mM NaCl. Results demonstrated that plant growth, stomatal conductance, and pigment contents were significantly lower at all Cd concentrations than the control plants. Quinoa plants exhibited improved growth and tolerance against Cd when grown at a lower level of salinity (150 mM NaCl) combined with Cd. In contrast, the elevated concentration of salinity (300 mM NaCl) combined with Cd reduced shoot and root growth of experimental plants more than 50%. Combined application of salinity and Cd increased Na (25-fold), while lessened the Cd (twofold) and K (1.5-fold) uptake. A blend of high concentrations of Na and Cd caused overproduction of H2O2 (eightfold higher than control) contents and triggered lipid peroxidation. The activities of antioxidant enzymes: ascorbate peroxidase (APX), catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) were 13, 12, 7 and ninefold higher than control to mitigate the oxidative stress. Due to restricted root to shoot translocation, and greater tolerance potential against Cd, the quinoa genotype, Puno, is suitable for phytostabilization of Cd in saline soils.

Multivariate characterization of biochemical and physiological attributes of quinoa (Chenopodium quinoa Willd.) genotypes exposed to nickel stress: implications for phytoremediation.

Nickel (Ni) is an essential element for plants; however, excessive uptake of Ni causes phytotoxicity in plants. The phytotoxic effects of Ni on the growth of quinoa and the underlaying mechanisms for Ni tolerance and phytoremediation are unknown. Hence, the present study investigated Ni tolerance and accumulation potential of two quinoa genotypes (Puno and Vikinga). Both genotypes were exposed to Ni (0, 100, 200, 300, and 400 µM) in half-strength Hoagland nutrient solution for three weeks. Results revealed that shoot and root lengths, biomass, stomatal conductance, and chlorophyll contents were decreased with the increase of Ni concentration. Excessive uptake of Ni resulted in the limited uptake of K by root and its translocation to shoot. Ni caused oxidative stress in plants by overproduction of H2O2 leading to lipid peroxidation of cell membranes. Genotype Puno showed greater tolerance to Ni than Vikinga based on tolerance index, lower bioconcentration factor, and translocation factor. Greater tolerance of Puno was mainly attributed to improved physiological responses and amelioration of oxidative stress by induction of antioxidant enzymes such as peroxidase (POD), catalase (CAT), superoxide dismutase (SOD), and ascorbate peroxidase (APX). It was revealed through multivariate analysis that Ni had strong negative correlations with growth and physiological attributes and positive associations with oxidative stress attributes. The study demonstrated genotypic variation in response to varying Ni concentrations and Puno performed better than Vikinga for phytostabilization of Ni-contaminated soils.

Nickel toxicity pretreatment attenuates salt stress by activating antioxidative system and ion homeostasis in tomato (Solanum lycopersicon L.): an interplay from mild to severe stress.

Plants antioxidative system is the first line of defense against oxidative stress caused secondarily by toxic ions under salinity. Plants with pre-activated antioxidative system can better adapt to salinity and can result in higher growth and yield. The current experiment was conducted to assess the adaptation of two tomato genotypes (Riogrande and Green Gold) with pre-activated antioxidative enzymes against salt stress. Tomato seedlings were exposed to mild stress (Ni: 0, 15 and 30 mg L-1) for three weeks to activate the antioxidative enzymes. The seedlings with pre-activated antioxidative enzymes were then grown under severe stress in hydroponics (0, 75 and 150 mM NaCl) and soil (control, 7.5 and 15 dS m-1) to check the adaptation, growth and yield. The results showed that Ni toxicity significantly enhanced activities of antioxidant enzymes (SOD, CAT, APX and POX) in both the genotypes and reduced growth with higher values in genotype Riogrande than Green Gold. The seedlings with pre-activated antioxidant enzymes showed better growth, low Na+ and high K+ uptake and maintained higher antioxidative enzymes activity than non-treated seedlings after four weeks of salt stress treatment in hydroponics. Similarly, the results in soil salinity treatment of the Ni pretreated seedlings showed higher yield characteristics (fruit yield per plant, average fruit weight and fruit diameter) than non-treated seedlings. However, Ni pretreatment had nonsignificant effect on tomato fruit quality characteristics like fruit dry matter percentage, total soluble solids, fruit juice pH and titratable acidity. The genotype Riogrande showed better growth, yield and fruit quality than Green Gold due to higher activity of antioxidant enzymes and better ion homeostasis as a result of Ni pretreatment. The results suggest that pre-activation antioxidant enzymes by Ni treatment proved to be an effective strategy to attenuate salt stress for better growth and yield of tomato plants.

Risk assessment of trace element accumulation in soil and Brassica oleracea after wastewater irrigation.

The risk assessment of trace elements has received substantial attention for the achievement of UN Sustainable Developmental Goals (UN-SDGs). The present study aimed to evaluate health and ecological risks associated with trace element accumulation in Brassica oleracea under wastewater irrigations from three different areas. This study, for the first time, compared the pros and cons of mixed water crop irrigation (wastewater with fresh/groundwater). A pot experiment was conducted to evaluate the buildup of eight trace elements (As, Cu, Cd, Mn, Fe, Pb, Ni and Zn) in soil and B. oleracea plants irrigated with wastewater alone and mixed with fresh/groundwater. Specific ecological [degree of contamination (Cd), potential ecological risk index (PERI), pollution load index (PLI), geo-accumulation index (Igeo)], phytoaccumulation [bioconcentration factor (BCF) and transfer factor (TF)] and health risk models [chronic daily intake (CDI), hazard quotient (HQ), cancer risk (CR)] were applied to assess the overall contamination of trace elements in the soil-plant-human system. Moreover, these indices were compared with the literature data. The concentration of Cd, Fe and Mn exceeded the threshold limits of 10, 500 and 200 mg kg-1, respectively, for agricultural soil. Overall, all the irrigation waters caused significant pollution load in soil indicating high ecological risk (Cd > 24, PERI > 380, Igeo > 5, PLI > 2). Not all the mixing treatments caused a reduction in trace element buildup in soil. The mixing of wastewater-1 with either groundwater or freshwater increased trace element levels in the soil as well as risk indices compared to wastewater alone. The BCF and TF values were > 1, respectively, for 66% and 7% treatments. Trace element concentration in plants and associated health risk were minimized in mixed wastewater treatments. There were 22% and 32% reduction in HQ and CR when wastewater was mixed with freshwater and 29% and 8% when mixed with groundwater. Despite total reduction, a great variation in % change in risk indices was observed with respect to the area of wastewater collection. Therefore, mixed water irrigation may be a good management strategy, but its recommendation depends on soil properties and composition of waters used for mixing. Moreover, it is recommended that the freshwater and wastewater of the particular area may be continuously monitored to avoid potential associated health hazards.

Cooperative Power-Domain NOMA Systems: An Overview.

Interference has been a key roadblock against the effectively deployment of applications for end-users in wireless networks including fifth-generation (5G) and beyond fifth-generation (B5G) networks. Protocols and standards for various communication types have been established and utilised by the community in the last few years. However, interference remains a key challenge, preventing end-users from receiving the quality of service (QoS) expected for many 5G applications. The increased need for better data rates and more exposure to multimedia information lead to a non-orthogonal multiple access (NOMA) scheme that aims to enhance spectral efficiency and link additional applications employing successive interference cancellation and superposition coding mechanisms. Recent work suggests that the NOMA scheme performs better when combined with suitable wireless technologies specifically by incorporating antenna diversity including massive multiple-input multiple-output architecture, data rate fairness, energy efficiency, cooperative relaying, beamforming and equalization, network coding, and space-time coding. In this paper, we discuss several cooperative NOMA systems operating under the decode-and-forward and amplify-and-forward protocols. The paper provides an overview of power-domain NOMA-based cooperative communication, and also provides an outlook of future research directions of this area.

The Structures of Heterogeneous Membranes and Their Interactions with an Anticancer Peptide: A Molecular Dynamics Study.

We conduct molecular dynamics simulations of model heterogeneous membranes and their interactions with a 24-amino acid peptide-NAF-144-67. NAF-144-67 is an anticancer peptide that selectively permeates and kills malignant cells; it does not permeate normal cells. We examine three membranes with different binary mixtures of lipids, DOPC-DOPA, DOPC-DOPS, and DOPC-DOPE, with a single peptide embedded in each as models for the diversity of biological membranes. We illustrate that the peptide organization in the membrane depends on the types of nearby phospholipids and is influenced by the charge and size of the head groups. The present study sheds light on early events of permeation and the mechanisms by which an amphiphilic peptide crosses from an aqueous solution to a hydrophobic membrane. Understanding the translocation mechanism is likely to help the design of new permeants.

In Vitro and In Vivo Anti-Arthritic Potential of Caralluma tuberculata N. E. Brown. and Its Chemical Characterization.

Present research was planned to assess the in vitro and in vivo anti-arthritic potential of Caralluma tuberculata N. E. Brown. methanolic (CTME) and aqueous (CTAQ) extracts. Chemical characterization was done by high-performance liquid chromatography and gas chromatography−mass spectrometry analysis. The Complete Freund's Adjuvant (CFA) was injected in left hind paw of rat at day 1 and dosing at 150, 300 and 600 mg/kg was started on the 8th day via oral gavage in all groups except normal and disease control rats (which were given distilled water), whereas methotrexate (intraperitoneal; 1 mg/kg/mL) was administered to standard control. The CTME and CTAQ exerted significant (p < 0.01−0.0001) in vitro anti-arthritic action. Both extracts notably reduced paw edema, and restored weight loss, immune organs weight, arthritic score, RBCs, ESR, platelet count, rheumatoid factor (RF), C-reactive protein, and WBCs in treated rats. The plant extracts showed significant (p < 0.05−0.0001) downregulation of tumor necrosis factor-α, Interleukin-6, -1ß, NF-κB, and cyclooxygenase-2, while notably upregulated IL-4, IL-10, I-κBα in contrast to disease control rats. The plant extracts noticeably (p < 0.001−0.0001) restored the superoxide dismutase and catalase activities and MDA levels in treated rats. Both extracts exhibited significant anti-arthritic potential. The promising potential was exhibited by both extracts probably due to phenolic, and flavonoids compounds.

Silicon-nanoparticles doped biochar is more effective than biochar for mitigation of arsenic and salinity stress in Quinoa: Insight to human health risk assessment.

The increasing contamination of soil with arsenic (As), and salinity has become a menace to food security and human health. The current study investigates the comparative efficacy of plain biochar (BC), and silicon-nanoparticles doped biochar (SBC) for ameliorating the As and salinity-induced phytotoxicity in quinoa (Chenopodium quinoa Willd.) and associated human health risks. Quinoa was grown on normal and saline soils (ECe 12.4 dS m-1) contaminated with As (0, 20 mg kg-1) and supplemented with 1% of BC or SBC. The results demonstrated that plant growth, grain yield, chlorophyll contents, and stomatal conductance of quinoa were decreased by 62, 44, 48, and 66%, respectively under the blended stress of As and salinity as compared to control. Contrary to this, the addition of BC to As-contaminated saline soil caused a 31 and 25% increase in plant biomass and grain yield. However, these attributes were increased by 45 and 38% with the addition of SBC. The H2O2 and TBARS contents were enhanced by 5 and 10-fold, respectively under the combined stress of As and salinity. The SBC proved to be more efficient than BC in decreasing oxidative stress through overexpressing of antioxidant enzymes. The activities of superoxide dismutase, peroxidase, and catalase were enhanced by 5.4, 4.6, and 11-fold with the addition of SBC in As-contaminated saline soil. Contamination of grains by As revealed both the non-carcinogenic and carcinogenic risks to human health, however, these effects were minimized with the addition of SBC. As accumulation in grains was decreased by 65-fold and 25-fold, respectively for BC and SBC in addition to As-contaminated saline soil. The addition of SBC to saline soils contaminated with As for quinoa cultivation is an effective approach for decreasing the food chain contamination and improving food security. However, more research is warranted for the field evaluation of the effectiveness of SBC in abating As uptake in other food crops cultivated on As polluted normal and salt-affected soils.

Pterostilbene improves CFA-induced arthritis and peripheral neuropathy through modulation of oxidative stress, inflammatory cytokines and neurotransmitters in Wistar rats.

Pterostilbene is a stilbene flavonoid that occurs naturally in various plants as well as produced by genetic engineering. It exhibits anti-inflammatory, analgesic, anti-oxidant and neuroprotective activities. This research was aimed to determine the potential of pterostilbene against arthritis and peripheral neuropathy in Complete Freund's Adjuvant (CFA) induced arthritis. Rat hind paw was injected with 0.1 ml CFA to induce arthritis. Standard control animals received oral methotrexate (3 mg/kg/week). Pterostilbene at 12.5, 25 and 50 mg/kg was given orally to different groups of arthritic rats from day 7-28 for 21 days. Pterostilbene significantly reduced paw diameter and retarded the decrease in body weight of arthritic rats. It profoundly (p < 0.05-0.0001) reduced lipid peroxidation and nitrites, while increased superoxide dismutase (SOD) in the liver tissue. Pterostilbene treatment significantly (p < 0.0001) reduced TNF-α and IL-6 levels. Pterostilbene markedly improved (p < 0.05-0.001) motor activity and showed analgesic effect in arthritic rats at 25 and 50 mg/kg as compared to disease control rats. Furthermore, it notably (p < 0.05-0.0001) increased SOD activity, nitrites, noradrenaline and serotonin levels in the sciatic nerve of arthritic rats. Treatment with pterostilbene also ameliorated the CFA-induced pannus formation, cartilage damage and synovial hyperplasia in the arthritic rat paws. It is determined from the current study that pterostilbene was effective in reducing CFA-induced arthritis in rats through amelioration of oxidative stress and inflammatory mediators. It was also effective to treat peripheral neuropathy through modulation of oxidative stress and neurotransmitters in sciatic nerves.

A Cancer Cell Membrane-Derived Biomimetic Nanocarrier for Synergistic Photothermal/Gene Therapy by Efficient Delivery of CRISPR/Cas9 and Gold Nanorods.

Bimodal synergistic therapy produces superadditive effect for enhanced therapeutic efficacy. However, how to efficiently and simultaneously deliver several kinds of therapeutic agents is still challenging. A cancer cell membrane-derived nanocarrier (mCas9-sGNRs) is proposed for synergistic photothermal/gene therapy (PTT/GT) by efficient delivery of clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) and gold nanorods (GNRs). In this approach, Cas9 proteins can be efficiently loaded inside the cell membranes (mCas9) by electrostatic interactions. Similarly, single-guide RNAs, which target survivin, can be loaded onto GNRs (sGNRs) through electrostatic interactions and encapsulated by mCas9. As a result, the nanodelivery systems present advantages in biocompatibility, homologous targeting capacity and loading efficiency of cargoes. In addition, significant antitumor effects is achieved by gene editing of survivin which induces anticancer activity and reduces heat tolerance of cancer cells caused by GNRs mediated PTT due to the downregulation of HSP70. These results indicate the nanotherapeutic platform leads to enhanced PTT/GT efficacy. Therefore, this work not only provides a general strategy to construct a versatile nanoplatform for loading and target delivery of several therapeutic cargos but will also be valuable for PTT/GT and other bimodal synergistic therapy.