Glycine betaine: A multifaceted protectant against salt stress in Indian mustard through ionic homeostasis, ROS scavenging and osmotic regulation.

Salt stress is a prevalent environmental issue that disrupts the redox balance and metabolic processes in plants, leading to reduced crop growth and productivity. Currently, over 6.74 million hectares in India are salt-affected, and about 75% of this land lies in states that are the major cultivators of edible oilseed crops (rapeseed-mustard). Therefore, this study focused on the efficacy of glycine betaine (GB) supplementation in mitigating the detrimental effects of salt stress in Brassica juncea L. (Indian mustard) plants. Indian mustard plants were subjected to salt stress [0, 50, 100, and 150 mM sodium chloride] 20 days after sowing (DAS), while a foliar spray of 20 mM GB was applied to the foliage at 50 and 70 DAS. The data showed that salt stress substantially reduced growth, photosynthetic rate, membrane stability, and yield by significantly increasing lipid peroxidation, ion toxicity, cell death, electrolyte leakage, and reactive oxygen species accumulation that triggered oxidative stress. Supplementation with 20 mM GB provided tolerance to plants against salt-induced toxicity since it substantially increased growth, biomass, water content, nutrient uptake, and photosynthetic efficiency. Additionally, GB enhances the accumulation of osmolytes, enhances the antioxidant defence system, improves ionic balance, and enhances cell viability. Taken together, the obtained data provides deeper insights into the beneficial effect of the exogenous GB application that could have biotechnological uses to enhance crop stress tolerance in challenging environments.

Effect of molecular crowders on ligand binding kinetics with G-quadruplex DNA probed by fluorescence correlation spectroscopy.

Guanine-rich single-stranded DNA folds into G-quadruplex DNA (GqDNA) structures, which play crucial roles in various biological processes. These structures are also promising targets for ligands, potentially inducing antitumor effects. While thermodynamic parameters of ligand/DNA interactions are well-studied, the kinetics of ligand interaction with GqDNA, particularly in cell-like crowded environments, remain less explored. In this study, we investigate the impact of molecular crowding agents (glucose, sucrose, and ficoll 70) at physiologically relevant concentrations (20% w/v) on the association and dissociation rates of the benzophenoxazine-core based ligand, cresyl violet (CV), with human telomeric antiparallel-GqDNA. We utilized fluorescence correlation spectroscopy (FCS) along with other techniques. Our findings reveal that crowding agents decrease the binding affinity of CV to GqDNA, with the most significant effect-a nearly three-fold decrease-observed with ficoll 70. FCS measurements indicate that this decrease is primarily due to a viscosity-induced slowdown of ligand association in the crowded environment. Interestingly, dissociation rates remain largely unaffected by smaller crowders, with only small effect observed in presence of ficoll 70 due to direct but weak interaction between the ligand and ficoll. These results along with previously reported data provide valuable insights into ligand/GqDNA interactions in cellular contexts, suggesting a conserved mechanism of saccharide crowder influence, regardless of variations in GqDNA structure and ligand binding mode. This underscores the importance of considering crowding effects in the design and development of GqDNA-targeted drugs for potential cancer treatment.

Curcumin nanogel and its efficacy against oxidative stress and inflammation in rat models of ischemic stroke.

Aim: The study was designed to develop and analyze curcumin nanoparticles. Methods: Curcumin nanoparticles were formulated and evaluated. Their efficacy in protecting against brain damage was investigated in a rat model of ischemic stroke, considering motor function, muscle strength and antioxidant enzyme activity. Results: Curcumin nanoparticles displayed a zeta potential of -55 ± 13.5 mV and an average particle size of 51.40 ± 21.70 nm. In ischemic stroke rat models, curcumin nanoparticle treatment significantly improved motor functions, and muscle strength and increased the activities of antioxidant enzymes like glutathione peroxidase, glutathione, glutathione S-transferase, superoxide dismutase and catalase, reducing oxidative stress and inflammation. Conclusion: Curcumin nanoparticles showed significant neuroprotective effects in ischemic stroke models.

[Box: see text].

Multipronged regulation of autophagy and apoptosis: emerging role of TRIM proteins.

TRIM proteins are characterized by their conserved N-terminal RING, B-box, and coiled-coil domains. These proteins are efficient regulators of autophagy, apoptosis, and innate immune responses and confer immunity against viruses and bacteria. TRIMs function as receptors or scaffold proteins that target substrates for autophagy-mediated degradation. Most TRIMs interact with the BECN1-ULK1 complex to form TRIMosomes, thereby efficiently targeting substrates to autophagosomes. They regulate the functions of ATG proteins through physical interactions or ubiquitination. TRIMs affect the lipidation of MAP1LC3B1 to form MAP1LC3B2, which is a prerequisite for phagophore and autophagosome formation. In addition, they regulate MTOR kinase and TFEB, thereby regulating the expression of ATG genes. TRIM proteins are efficient regulators of apoptosis and are crucial for regulating cell proliferation and tumor formation. Many TRIM proteins regulate intrinsic and extrinsic apoptosis via the cell surface receptors TGFBR2, TNFRSF1A, and FAS. Mitochondria modulate the anti- and proapoptotic functions of BCL2, BAX, BAK1, and CYCS. These proteins use a multipronged approach to regulate the intrinsic and extrinsic apoptotic pathways, culminating in coordinated activation or inhibition of the initiator and executor CASPs. Furthermore, TRIMs can have a dual effect in determining cell fate and are therefore crucial for cellular homeostasis. In this review, we discuss mechanistic insights into the role of TRIM proteins in regulating autophagy and apoptosis, which can be used to better understand cellular physiology. These findings can be used to develop therapeutic interventions to prevent or treat multiple genetic and infectious diseases.

Sesamin's Therapeutic Actions on Cyclophosphamide-Induced Hepatotoxicity, Molecular Mechanisms, and Histopathological Characteristics.

Cyclophosphamide, an alkylating agent integral to specific cancer chemotherapy protocols, is often curtailed in application owing to its significant hepatotoxic side effects. Therefore, this study was conducted to assess the hepatoprotective potential of sesamin, a plant-originated antioxidant, using rat models. The rats were divided into five groups: a control group received only the vehicle for six days; a cyclophosphamide group received an intraperitoneal (i.p.) single injection of cyclophosphamide (150 mg/kg) on day four; a sesamin group received a daily high oral dose (20 mg/kg) of sesamin for six days; and two groups were pretreated with oral sesamin (10 and 20 mg/kg daily from day one to day six) followed by an i.p. injection of cyclophosphamide on day four. The final and last sesamin dose was administered 24 h before euthanasia. At the end of the experiment, blood and liver tissue were collected for biochemical and histopathological assessments. The results indicated significantly increased liver markers (AST, ALT, ALP, and BIL), cytokines (TNFα and IL-1ß), caspase-3, and malondialdehyde (MDA) in the cyclophosphamide group as compared to the normal control. Additionally, there was a significant decline in antioxidants (GSH) and antioxidant enzymes (CAT and SOD), but the sesamin treatment reduced liver marker enzymes, cytokines, and caspase-3 and improved antioxidants and antioxidant enzymes. Thus, sesamin effectively countered these alterations and helped to normalize the histopathological alterations. In conclusion, sesamin demonstrated the potential for attenuating cyclophosphamide-induced hepatotoxicity by modulating cytokine networks, apoptotic pathways, and oxidative stress, suggesting its potential role as an adjunct in chemotherapy to reduce hepatotoxicity.

Exogenous epibrassinolide application improves essential oil biosynthesis and trichome development in peppermint via modulating growth and physicochemical processes.

Peppermint has gained a promising status due to the presence of a high proportion of bioactive compounds, especially menthol. Due to its pharmacological efficacy, the demand for its plant-based bioactive compounds necessitates its cultivation worldwide. Brassinosteroids are polyhydroxylated sterol derivatives that regulate diverse processes and control many agronomic traits during plant growth and development. A factorial randomised pot experiment was performed in the net house to investigate the effect of 24-Epibrassinolide (EBL) on the growth, physiology, essential oil content, stomatal behaviour and trichome development of the three cultivars of peppermint. Four levels of foliage-applied EBL, viz. 0, 10-5, 10-6 and 10-7 M were applied to the three cultivars of peppermint (Kukrail, Pranjal and Tushar). Among the different treatments of EBL, the application of 10-6 M increased shoot length by 38.84, 37.59 and 36.91%, root length by 36.73, 29.44 and 33.47%, chlorophyll content by 24.20, 22.48 and 23.32%, PN by 32.88, 32.61 and 33.61%, EO content by 32.72, 30.00 and 28.84%, EO yield per plant by 66.66, 77.77 and 73.33% and menthol yield per plant by 127.27, 110 and 118.18% in Kukrail, Tushar and Pranjal respectively, compared with their respective control plants. Further, the 10-6 M EBL exhibited improved trichome size and density, cellular viability and menthol content of the oil analysed from scanning electron microscopy, confocal laser scanning microscopy and GC-MS respectively as compared to the control. In conclusion, out of different levels of EBL, two sprays of 10-6 M EBL proved effective in enhancing the morphophysiological features and productivity of mint plants, particularly for cultivar Kukrail.

Thymoquinone Ameliorates Carfilzomib-Induced Renal Impairment by Modulating Oxidative Stress Markers, Inflammatory/Apoptotic Mediators, and Augmenting Nrf2 in Rats.

Chemotherapy-induced kidney damage is an emerging problem that restricts cancer treatment effectiveness. The proteasome inhibitor carfilzomib (CFZ) is primarily used to treat multiple myeloma and has been associated with severe renal injury in humans. CFZ-induced nephrotoxicity remains an unmet medical need, and there is an urgent need to find and develop a nephroprotective and antioxidant therapy for this condition. Thymoquinone (TQ) is a bioactive compound that has been isolated from Nigella sativa seeds. It has a wide range of pharmacological properties. Therefore, this experimental design aimed to study the effectiveness of TQ against CFZ-induced renal toxicity in rats. The first group of rats was a normal control (CNT); the second group received CFZ (4 mg/kg b.w.); the third and fourth groups received TQ (10 and 20 mg/kg b.w.) 2 h before receiving CFZ; the fifth group received only TQ (20 mg/kg b.w.). This experiment was conducted for 16 days, and at the end of the experiment, blood samples and kidney tissue were collected for biochemical assays. The results indicated that administration of CFZ significantly enhanced serum marker levels such as BUN, creatinine, and uric acid in the CFZ group. Similarly, it was also noticed that CFZ administration induced oxidative stress by reducing antioxidants (GSH) and antioxidant enzymes (CAT and SOD) and increasing lipid peroxidation. CFZ treatment also enhanced the expression of IL-1ß, IL-6, and TNF-α production. Moreover, CFZ increased caspase-3 concentrations and reduced Nrf2 expression in the CFZ-administered group. However, treatment with 10 and 20 mg/kg TQ significantly decreased serum markers and increased antioxidant enzymes. TQ treatment considerably reduced IL-1ß, IL-6, TNF-α, and caspase-3 concentrations. Overall, this biochemical estimation was also supported by histopathological outcomes. This study revealed that TQ administration significantly mitigated the negative effects of CFZ treatment on Nrf2 expression. Thus, it indicates that TQ may have utility as a potential drug to prevent CFZ-induced nephrotoxicity in the future.

CRISPR­based diagnostic approaches: Implications for rapid management of future pandemics (Review).

Sudden viral outbreaks have increased in the early part of the 21st century, such as those of severe acute respiratory syndrome coronavirus (SARS­CoV), Middle East respiratory syndrome corona virus, and SARS­CoV­2, owing to increased human access to wildlife habitats. Therefore, the likelihood of zoonotic transmission of human­associated viruses has increased. The emergence of severe acute respiratory syndrome coronavirus 2 in China and its spread worldwide within months have highlighted the need to be ready with advanced diagnostic and antiviral approaches to treat newly emerging diseases with minimal harm to human health. The gold­standard molecular diagnostic approaches currently used are time­consuming, require trained personnel and sophisticated equipment, and therefore cannot be used as point­of­care devices for widespread monitoring and surveillance. Clustered regularly interspaced short palindromic repeats (CRISPR)­associated (Cas) systems are widespread and have been reported in bacteria, archaea and bacteriophages. CRISPR­Cas systems are organized into CRISPR arrays and adjacent Cas proteins. The detection and in­depth biochemical characterization of class 2 type V and VI CRISPR­Cas systems and orthologous proteins such as Cas12 and Cas13 have led to the development of CRISPR­based diagnostic approaches, which have been used to detect viral diseases and distinguish between serotypes and subtypes. CRISPR­based diagnostic approaches detect human single nucleotide polymorphisms in samples from patients with cancer and are used as antiviral agents to detect and destroy viruses that contain RNA as a genome. CRISPR­based diagnostic approaches are likely to improve disease detection methods in the 21st century owing to their ease of development, low cost, reduced turnaround time, multiplexing and ease of deployment. The present review discusses the biochemical properties of Cas12 and Cas13 orthologs in viral disease detection and other applications. The present review expands the scope of CRISPR­based diagnostic approaches to detect diseases and fight viruses as antivirals.

Trastuzumab-Mediated Cardiotoxicity and Its Preventive Intervention by Zingerone through Antioxidant and Inflammatory Pathway in Rats.

Trastuzumab (TZB) is a new medicine, used to treat cancers of the breast and stomach. However, the cardiotoxic potential of this drug edges out its clinical advantages. The present study was designed to find out the effect of zingerone against trastuzumab-mediated cardiotoxicity in rats. In this study, five groups of rats with eight animals in each group were used. Group 1 was treated with normal saline, as a normal control (NC); Group 2 was treated with TZB (6 mg/kg/week-for five weeks) intraperitoneally as a toxic control. Groups 3 and 4 were pre-treated with zingerone (50 and 100 mg/kg, as per their body weight orally) along with five doses of TZB for five weeks, and Group 5 was treated with zingerone (100 mg/kg, body weight orally) as a control. TZB treatment showed cardiotoxicity as evidenced by increased levels of aspartate aminotransferase (AST), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and lipid peroxidation (LPO) and decreased level of glutathione (GSH), and antioxidant enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s- transferase (GST), catalase (CAT), and superoxide dismutase (SOD) activities. Zingerone pre-treatment significantly decreased the levels of AST, CK-MB, LDH, and LPO and increased GSH and antioxidant enzymes content toward their normal level. In the TZB-alone administered group, inflammatory cytokines (IL-2 and TNF-α) levels were also elevated. Pre-treatment with zingerone restored the level of IL-2 and TNF-α toward normal level. The current findings undoubtedly demonstrated zingerone's cardioprotective nature against TZB-mediated cardiotoxicity in rats with the evidence of histopathological recall.

Capsaicin Ameliorates the Cyclophosphamide-Induced Cardiotoxicity by Inhibiting Free Radicals Generation, Inflammatory Cytokines, and Apoptotic Pathway in Rats.

Cyclophosphamide is an antineoplastic agent that has a broad range of therapeutic applications; however, it has numerous side effects, including cardiotoxicity. Furthermore, chili peppers contain a substance called capsaicin, having antioxidant and anti-inflammatory effects. Thus, this research paper focuses on the potential mechanism of capsaicin's cardioprotective activity against cyclophosphamide-induced cardiotoxicity by measuring the expression of oxidative and inflammatory marker such as interleukins and caspases. The following groups of rats were randomly assigned: only vehicle given for 6 days (control group); cyclophosphamide 200 mg/kg intraperitoneal on 4th day only (positive control group); capsaicin 10 mg/kg orally given for 6 days followed by cyclophosphamide 200 mg/kg on 4th day of treatment; capsaicin 20 mg/kg orally for six days followed by cyclophosphamide 200 mg/kg on 4th day of treatment; and maximum amount of capsaicin alone (20 mg/kg) orally for six days. Using ELISA kits, it was found that the cyclophosphamide administration significantly increased the levels of lactate dehydrogenase, troponin-I (cardiac cell damage marker), lipid peroxidation, triglyceride, interleukin-6, tumor necrosis factor-alpha, and caspase 3. However, it markedly reduced the antioxidant enzymes catalase and glutathione levels. Both doses of capsaicin could reverse cardiac cell damage markers, as shown by a significant decline in (lactate dehydrogenase and troponin-I). In addition, capsaicin significantly reduced the cytokine levels (interleukin-6 and tumor necrosis factor-alpha), caspase 3, lipid peroxidation, and triglycerides. However, capsaicin treatment significantly raised the antioxidant content of enzymes such as glutathione and catalase. The capsaicin-treated group restored the oxidative parameter's imbalance and generated considerable protection against cardiomyocyte harm from cyclophosphamide in male Wistar rats. These protective effects might be beneficial against the negative impacts of cyclophosphamide when used to treat cancer and immune-mediated diseases.

Therapeutic Potential of Capsaicin against Cyclophosphamide-Induced Liver Damage.

Cyclophosphamide (CPM) is a classical alkylating agent used in different cancer chemotherapy regimens and is restricted due to severe adverse effects, including hepatotoxicity. Natural or plant-derived antioxidants such as capsaicin were utilized in this study to examine the hepatoprotective benefits against cyclophosphamide-induced hepatotoxicity. The rats were divided into five groups: a normal control group, a toxic group (CPM), an intraperitoneal injection of a single dose of 200 mg/kg b.w. on the fourth day, a pretreated group with two doses of CPS (10 mg and 20 mg/kg b.w.) orally for six consecutive days, and an intraperitoneal administration of 200 mg/kg b.w. on the fourth day of treatment. The fifth group was administered with the highest dose of CPS (20 mg/kg b.w.) orally for six consecutive days. After 24 h of administration of CPS, the rats were anesthetized, blood was collected, and the serum enzyme toxicity was evaluated. After the blood sampling and euthanasia of all the animals, the liver was isolated for further toxicity and histopathological examination. The results revealed that serum liver markers (AST, ALT, ALP, BLI) significantly increased after CPM administration, but were subsequently restored after CPS treatment with both doses. In addition, lipid peroxidation (MDA), inflammatory cytokines (IL-1ß, TNF-α), and apoptotic markers (Caspase-3) increased, and antioxidant enzymes (GSH, CAT, SOD) were significantly decreased after CPM administration, and it was re-established by CPS treatment. However, CPS effectively protected against the CPM-induced histopathological architects of liver tissues. In conclusion, CPS attenuates CPM-induced hepatotoxicity via modulating oxidative stress, apoptotic signals, and cytokine pathway. Therefore, CPS could play a significant role as a supplement during the chemotherapy of patients.

Nephroprotective Effect of Diosmin against Cisplatin-Induced Kidney Damage by Modulating IL-1ß, IL-6, TNFα and Renal Oxidative Damage.

Cisplatin (CP) is a platinum compound of the alkylating agent class that is used for the treatment of various types of cancer. However, CP treatments in cancer patients are accountable for nephrotoxicity, as it is a major adverse effect. Hence, this research study was proposed to investigate the nephroprotective effect of diosmin, a flavonoid glycoside of hesperidin derivatives against cisplatin-induced kidney damage. Wistar rats received a single intraperitoneal (i.p) injection of CP (7.5 mg/kg, i.p) to induce nephrotoxicity. The administration of CP significantly (p < 0.001) increased the markers of kidney function test (creatinine, blood urea nitrogen, and uric acid) and demonstrated histopathological changes in the kidney of the CP-treated nephrotoxic group. In addition, the CP-treated nephrotoxic group demonstrated a significant (p < 0.001) increase in lipid peroxidation (LPO) levels and depleted activities of reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT).However, diosmin (100 and 200 mg/kg) treatments significantly reduced the elevated levels of kidney function test parameters and restored structural changes in the kidney (p < 0.001). The administration of diosmin (100 and 200 mg/kg) significantly (p < 0.001) reduced LPO levels, increased GSH content and showed improvements in the activities of GPx, GR, SOD and CAT. The markers of inflammatory cytokines such as IL-1ß, IL-6 and TNFα significantly (p < 0.001) increased in the CP-treated nephrotoxic group, whereas diosmin (100 and 200 mg/kg) treatments significantly (p < 0.001) reduced the elevated levels of these cytokines. The findings of this research demonstrate the nephroprotective effect of diosmin against CP-induced kidney damage. Therefore, we conclude that diosmin may be used as a supplement in the management of nephrotoxicity associated with CP treatments in cancer patients.

Hepatoprotective potential of diosmin against hepatotoxic effect of isoniazid and rifampin in wistar rats.

OBJECTIVE: The treatment of tuberculosis with isoniazid and rifampin is associated with hepatocellular damage. Therefore, the study was designed to evaluate the hepatoprotective potential of diosmin against hepatotoxic effect of isoniazid and rifampin in Wistar rats. METHODS: Hepatotoxicity was induced by administering isoniazid and rifampin (100 mg/kg), whereas diosmin was given as treatment control. Markers of liver function (ALT, AST, ALP and bilirubin), inflammatory cytokines (TNFα, IL-6 and IL-1ß), apoptosis (caspase-3), oxidative stress parameters (LPO, GSH, CAT and SOD) and histological changes in liver were assessed in normal, hepatotoxic control and treatment groups. RESULTS: The administration of isoniazid and rifampin significantly increased markers of liver dysfunction (ALT, AST, ALP and bilirubin), cytokines (TNFα, IL-6 and IL-1ß) and apoptosis (caspase-3). However, daily dosing of diosmin significantly reduced these markers of liver dysfunction, inflammatory cytokines and apoptosis to near normal levels. Additionally, markers of hepatocellular oxidative stress parameters were significantly altered as evident from increased LPO level and decreased endogenous antioxidants such as GSH, SOD and CAT in isoniazid-and rifampin-treated hepatotoxic group. It was observed that diosmin treatment reduced high levels of LPO and demonstrated significant improvement in antioxidant levels. Histological studies of liver also supported our biochemical findings, which are also manifested as diosmin treatment exhibited protection against hepatocellular degeneration and inflammation. CONCLUSION: Results of the present study demonstrate hepatoprotective potential of diosmin against isoniazid-and rifampin-treated hepatotoxicity. Thus, we conclude that diosmin may be used along with anti-tubercular drugs (isoniazid and rifampin) in tuberculosis patients to overcome their hepatotoxic adverse effect.

Zingerone Attenuates Carfilzomib-Induced Cardiotoxicity in Rats through Oxidative Stress and Inflammatory Cytokine Network.

Carfilzomib (CFZ) is an anticancer medication acting as a selective proteasome inhibitor. However, it can cause cardiovascular problems, increasing mortality and morbidity. This study aimed to investigate whether zingerone (ZRN) could help reduce carfilzomib-induced cardiotoxicity in Wistar albino rats. Rats were divided into five groups of six animals each. The first group received normal saline as a control (NC); the second group received multiple doses (six) of CFZ (4 mg/kg) intraperitoneally (IP); the third and fourth groups received zingerone (50 mg/kg and 100 mg/kg oral) along with six doses of CFZ for 16 days; and the fifth group received only 100 mg/kg zingerone orally. Hematological, biochemical, oxidative stress, and histopathological studies confirmed the findings of CFZ-induced cardiotoxicity. We found that ZRN significantly attenuated the effects of CFZ on oxidative stress by enhancing the antioxidant properties of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Additionally, ZRN reduces inflammatory cytokines and apoptotic markers, such as IL-1ß, IL-6, TNFα, and caspase-3. Overall, zingerone prevents carfilzomib-induced cardiotoxicity in rats, as evidenced by histopathological studies.

Salicylic Acid Priming Regulates Stomatal Conductance, Trichome Density and Improves Cadmium Stress Tolerance in Mentha arvensis L.

The application of phytohormones through seed priming could enhance quality of important medicinal and aromatic plants (MAPs) under heavy metal stress. We evaluated the potential of salicylic acid (SA) priming for overcoming the adverse effects of cadmium stress in Mentha arvensis L. plants. Suckers of plants were primed with SA before transplanting them into soil. At 30 days after transplanting, two doses (50 and 100 µm) of CdCl2 were applied to the soil. Both Cd treatments altered plant growth, photosynthetic pigments, leaf gas exchange attributes, and mineral nutrient contents. The 50 and 100 µm Cd treatments increased endogenous Cd content by 97.95 and 98.03%, electrolyte leakage (EL) by 34.21 and 44.38%, hydrogen peroxide (H2O2) by 34.71 and 55.80%, malondialdehyde (MDA) by 53.08 and 63.15%, and superoxide content (O2 -•) by 24.07 and 38.43%, respectively. Cd triggered the up-regulation of antioxidant enzyme activities (superoxide dismutase, SOD; catalase, CAT; ascorbate peroxidase, APX; and glutathione reductase GR) and increased osmolyte biosynthesis and, interestingly, secondary metabolite (SM) accumulation. The presence of SA and Cd had an additive effect on these parameters. Nevertheless, plants primed with SA regulated stomatal conductance under Cd stress. SA priming to menthol mint plants under Cd stress overcome the effects of Cd stress while increasing SMs.

Plant growth regulators improve growth, photosynthesis, mineral nutrient and antioxidant system under cadmium stress in menthol mint (Mentha arvensis L.).

Menthol mint (Mentha arvensis L.) cultivation is significantly affected by the heavy metals like cadmium (Cd) which also imposes severe health hazards. Two menthol mint cultivars namely Kosi and Kushal were evaluated under Cd stress conditions. Impact of plant growth regulators (PGRs) like salicylic acid (SA), gibberellic acid (GA3) and triacontanol (Tria) on Cd stress tolerance was assessed. Reduced growth, photosynthetic parameters, mineral nutrient concentration, and increased oxidative stress biomarkers like electrolyte leakage, malondialdehyde, and hydrogen peroxide contents were observed under Cd stress. Differential upregulation of proline content and antioxidant activities under Cd stress was observed in both the cultivars. Interestingly, low electrolyte leakage, lipid peroxidation, hydrogen peroxide and Cd concentration in leaves were observed in Kushal compared to Kosi. Among all the PGRs tested, SA proved to be the best in improving Cd-stress tolerance in both the cultivars but Kushal responded better than Kosi.

Cdr1p highlights the role of the non-hydrolytic ATP-binding site in driving drug translocation in asymmetric ABC pumps.

ATP-binding cassette (ABC) transporters couple ATP binding and hydrolysis to the translocation of allocrites across membranes. Two shared nucleotide-binding sites (NBS) participate in this cycle. In asymmetric ABC pumps, only one of them hydrolyzes ATP, and the functional role of the other remains unclear. Using a drug-based selection strategy on the transport-deficient mutant L529A in the transmembrane domain of the Candida albicans pump Cdr1p; we identified a spontaneous secondary mutation restoring drug-translocation. The compensatory mutation Q1005H was mapped 60 Å away, precisely in the ABC signature sequence of the non-hydrolytic NBS. The same was observed in the homolog Cdr2p. Both the mutant and suppressor proteins remained ATPase active, but remarkably, the single Q1005H mutant displayed a two-fold reduced ATPase activity and a two-fold increased drug-resistance as compared to the wild-type protein, pointing at a direct control of the non-hydrolytic NBS in substrate-translocation through ATP binding in asymmetric ABC pumps.

A rare case of Rhupus syndrome with Hashimoto's thyroiditis, associated adverse effect of drugs and incidental findings.

The term Rhupus is coded for the individuals who have rheumatoid like arthritis with erosions and fulfil the criteria for both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Abnormal Th2 cell plays a central role in SLE while Th1 participate in RA. Thus the overlap of SLE and RA has a very low incidence (0.01%-0.2%) in patient with arthritis. This 40-year-old male patient presented with complains of severe multiple joint pain with progressive deformities, diminished vision from last 2 months, redness on back, headache and swelling over scalp. As this patient had history of severe trauma that was considered as a precipitating factor for ongoing chronic inflammatory disorder. Posterior subcapsular cataract was explained by prolong use of systemic steroid and rashes on the lower back due to sulfasalazine. Radioimaging study revealed arachnoid cyst and calcified projection arising from outer table of skull, which was kept under observation.

Salicylic acid enhances nickel stress tolerance by up-regulating antioxidant defense and glyoxalase systems in mustard plants.

The present study identified inverse relationships between nickel (Ni) levels and growth, photosynthesis and physio-biochemical attributes, but increasing levels of Ni stress enhanced methylglyoxal, electrolyte leakage, hydrogen peroxide, and lipid peroxidation content. Exogenous application of salicylic acid (SA) (10-5 M) ameliorated the ill-effects of Ni by restoring growth, photosynthesis and physio-biochemical attributes and increasing the activities of enzymes associated with antioxidant systems, especially the ascorbate-glutathione (AsA-GSH) cycle and glyoxalase system. In addition, SA application to Ni-stressed plants had an additive effect on the activities of the ascorbate and glutathione pools, and the AsA-GSH cycle enzymes (ascorbate peroxidase, monodehydroascorbate reductase, dehydroascorbate reductase, glutathione reductase), superoxide dismutase, catalase, glutathione S-transferase, and osmolyte biosynthesis). This trend also follows in glyoxalase system viz. glyoxalase I and glyoxalase II enzymes. Nevertheless, exogenous SA supplementation restored mineral nutrient contents. Principal component analysis showed that growth, photosynthesis, and mineral nutrient parameters were positively correlated with each other and negatively correlated with antioxidant enzymes and oxidative stress biomarkers. Hence, SA is an alternative compound with potential application in the phytoremediation of Ni.

Thymoquinone and fluoxetine alleviate depression via attenuating oxidative damage and inflammatory markers in type-2 diabetic rats.

The study was designed to find out the effect of thymoquinone (TQ) alone and combination of TQ + fluoxetine in depression of type-2 diabetic rats. Glucose level was significantly decreased in TQ alone treated group, whereas no significant change was recorded when TQ was combined with fluoxetine. Administration of TQ alone and combination of TQ and fluoxetine significantly decreased immobility time, increased latency to immobility and increased locomotor activity. Treatment with TQ alone significantly decreased level of TBARS, increased GSH and restored the activities of antioxidant enzymes (GPx, GR & CAT). However, TQ and fluoxetine combination reduced TBARS level, increased GSH content but no change in the antioxidant enzymes activities. Inflammatory markers (IL-1ß, IL-6 & TNF-α) levels were significantly reduced after the administration of TQ alone and TQ + fluoxetine. The study suggests that combination of TQ and fluoxetine can be used to control depression in type-2 diabetes mellitus.