Microglial Sp1 induced LRRK2 upregulation in response to manganese exposure, and 17ß-estradiol afforded protection against this manganese toxicity.

Chronic exposure to elevated levels of manganese (Mn) causes a neurological disorder referred to as manganism, presenting symptoms similar to those of Parkinson's disease (PD), yet the mechanisms by which Mn induces its neurotoxicity are not completely understood. 17ß-estradiol (E2) affords neuroprotection against Mn toxicity in various neural cell types including microglia. Our previous studies have shown that leucine-rich repeat kinase 2 (LRRK2) mediates Mn-induced inflammatory toxicity in microglia. The LRRK2 promoter sequences contain three putative binding sites of the transcription factor (TF), specificity protein 1 (Sp1), which increases LRRK2 promoter activity. In the present study, we tested if the Sp1-LRRK2 pathway plays a role in both Mn toxicity and the protection afforded by E2 against Mn toxicity in BV2 microglial cells. The results showed that Mn induced cytotoxicity, oxidative stress, and tumor necrosis factor-α production, which were attenuated by an LRRK2 inhibitor, GSK2578215A. The overexpression of Sp1 increased LRRK2 promoter activity, mRNA and protein levels, while inhibition of Sp1 with its pharmacological inhibitor, mithramycin A, attenuated the Mn-induced increases in LRRK2 expression. Furthermore, E2 attenuated the Mn-induced Sp1 expression by decreasing the expression of Sp1 via the promotion of the ubiquitin-dependent degradation pathway, which was accompanied by increased protein levels of RING finger protein 4, the E3-ligase of Sp1, Sp1 ubiquitination, and SUMOylation. Taken together, our novel findings suggest that Sp1 serves as a critical TF in Mn-induced LRRK2 expression as well as in the protection afforded by E2 against Mn toxicity through reduction of LRRK2 expression in microglia.

Evaluating Plant Growth-Promoting Rhizobacteria to Improve the Productivity of Forage Pearl Millet.

India's livestock industry is grappling with a shortage of green fodder, necessitating concerted efforts to boost organized production and ensure a sufficient supply of high-quality forages, crucial for formulating nutritionally balanced, cost-effective, and rumen-healthy animal diets. Hence, this study was conducted to assess the plant growth-promoting characteristics of liquid microbial inoculants and their impact on the yield of forage pearl millet. The bacterial cultures utilized included Sphingobacterium sp., Stenotrophomonas maltophilia, and an isolate from vegetable cowpea, subsequently identified as Burkholderia seminalis. These cultures were initially characterized for their plant growth-promoting traits at different temperature and physiological conditions. All the bacterial cultures were found promising for PGPR traits over varied temperature conditions and the optimum activity was recorded at 40 °C, with tolerance to saline and drought stresses as well as wide pH and temperature ranges. A field experiment was conducted during kharif 2020 at Punjab Agricultural University, Ludhiana and Punjab Agricultural University, Regional Research Station, Bathinda, involving combinations of liquid microbial inoculants along with 100% Recommended Dose of Fertilizer (RDF). It was observed that the treatment including B. seminalis + S. maltophilia along with RDF yielded the highest green fodder and dry matter yield, In conclusion, it is evident that the utilization of these liquid microbial inoculants holds significant potential for playing a pivotal role in the integrated nutrient management of forage pearl millet, thereby contributing to heightened productivity and sustained soil health.

ReLo is a simple and rapid colocalization assay to identify and characterize direct protein-protein interactions.

The characterization of protein-protein interactions (PPIs) is fundamental to the understanding of biochemical processes. Many methods have been established to identify and study direct PPIs; however, screening and investigating PPIs involving large or poorly soluble proteins remains challenging. Here, we introduce ReLo, a simple, rapid, and versatile cell culture-based method for detecting and investigating interactions in a cellular context. Our experiments demonstrate that ReLo specifically detects direct binary PPIs. Furthermore, we show that ReLo bridging experiments can also be used to determine the binding topology of subunits within multiprotein complexes. In addition, ReLo facilitates the identification of protein domains that mediate complex formation, allows screening for interfering point mutations, and it is sensitive to drugs that mediate or disrupt an interaction. In summary, ReLo is a simple and rapid alternative for the study of PPIs, especially when studying structurally complex proteins or when established methods fail.

Unravelling the link between SARS-CoV-2 mutation frequencies, patient comorbidities, and structural dynamics.

Genomic surveillance is crucial for tracking emergence and spread of novel variants of pathogens, such as SARS-CoV-2, to inform public health interventions and to enforce control measures. However, in some settings especially in low- and middle- income counties, where sequencing platforms are limited, only certain patients get to be selected for sequencing surveillance. Here, we show that patients with multiple comorbidities potentially harbour SARS-CoV-2 with higher mutation rates and thus deserve more attention for genomic surveillance. The relationship between the patient comorbidities, and type of amino acid mutations was assessed. Correlation analysis showed that there was a significant tendency for mutations to occur within the ORF1a region for patients with higher number of comorbidities. Frequency analysis of the amino acid substitution within ORF1a showed that nsp3 P822L of the PLpro protease was one of the highest occurring mutations. Using molecular dynamics, we simulated that the P822L mutation in PLpro represents a system with lower Root Mean Square Deviation (RMSD) fluctuations, and consistent Radius of gyration (Rg), Solvent Accessible Surface Area (SASA) values-indicate a much stabler protein than the wildtype. The outcome of this study will help determine the relationship between the clinical status of a patient and the mutations of the infecting SARS-CoV-2 virus.

Sorafenib tosylate-loaded nanosuspension: preparation, optimization, and in vitro cytotoxicity study against human HepG2 carcinoma cells.

This study aimed to optimize nanosuspension of sorafenib tosylate (an anticancer hydrophobic drug molecule) using a central composite design. Nanosuspension was prepared using a nanoprecipitation-ultrasonication approach. FTIR and DSC analyses demonstrated that the drug and excipients were physicochemically compatible. X-ray powder diffraction analysis confirmed amorphous form of the payload in the formulation. The optimized formulation (batch NSS6) had a zeta potential of -18.1 mV, a polydispersity of 0.302, and a particle size of 97.11 nm. SEM analysis confirmed formation of rod-shaped particles. After 24 h, about 64.45% and 86.37% of the sorafenib tosylate was released in pH 6.8 and pH 1.2, respectively. The MTT assay was performed on HepG2 cell lines. IC50 value of the optimized batch was 39.4 µg/mL. The study concluded that sorafenib tosylate nanosuspension could be a promising approach in the treatment of hepatocellular cancer.

Glial Heterotopia of the Middle Ear: First Case in Indian Literature.

A 66-years-old female presented with impaired hearing of two-year duration and a recent ear discharge. High-resolution computed tomography and intra-operative findings showed a mass lesion in the right middle ear cavity that was unconnected with the brain. A histopathological diagnosis of glial heterotopia was made and an etiopathogenic hypothesis was analysed.

Characterizing Risk Factors for Hospitalization and Clinical Characteristics in a Cohort of COVID-19 Patients Enrolled in the GENCOV Study.

The GENCOV study aims to identify patient factors which affect COVID-19 severity and outcomes. Here, we aimed to evaluate patient characteristics, acute symptoms and their persistence, and associations with hospitalization. Participants were recruited at hospital sites across the Greater Toronto Area in Ontario, Canada. Patient-reported demographics, medical history, and COVID-19 symptoms and complications were collected through an intake survey. Regression analyses were performed to identify associations with outcomes including hospitalization and COVID-19 symptoms. In total, 966 responses were obtained from 1106 eligible participants (87% response rate) between November 2020 and May 2022. Increasing continuous age (aOR: 1.05 [95%CI: 1.01-1.08]) and BMI (aOR: 1.17 [95%CI: 1.10-1.24]), non-White/European ethnicity (aOR: 2.72 [95%CI: 1.22-6.05]), hypertension (aOR: 2.78 [95%CI: 1.22-6.34]), and infection by viral variants (aOR: 5.43 [95%CI: 1.45-20.34]) were identified as risk factors for hospitalization. Several symptoms including shortness of breath and fever were found to be more common among inpatients and tended to persist for longer durations following acute illness. Sex, age, ethnicity, BMI, vaccination status, viral strain, and underlying health conditions were associated with developing and having persistent symptoms. By improving our understanding of risk factors for severe COVID-19, our findings may guide COVID-19 patient management strategies by enabling more efficient clinical decision making.

Effect of popping and malting processing techniques on physiochemical, antinutrients and antioxidant properties of millets flour.

The present investigation aimed to evaluate the effect of popping and malting on nutritional characteristics in millets. Five genotypes each of sorghum, finger millet and pearl millet were analyzed after popping and malting process. The physiochemical, antinutrients and antioxidant properties were observed in raw, popped and malted millet flours. The crude protein and energy were found to increase when popped and decrease after malting, whereas crude fibre content significantly decreased in popped and malted flours of all millets over the raw flours. A significant rise in total soluble carbohydrates was seen after raw millets were processed. Malting resulted in increase of enzymatic activities (Lipoxygenase and alpha-amylase). Alkaloids and antioxidants (FRAP, DPPH and Ascorbic acid) increased whereas starch and amylose decreased after processing techniques compared to raw flour. Total phenols and tannins increased and reduction in antinutrients i.e. phytic acid, saponins and oxalate was seen in processed millet flours over raw. The results showed that the household processing techniques i.e. popping and malting improved the nutritional composition and antioxidant potential with simultaneous decrease in antinutritional components in all millet genotypes. Raw and processed pearl millet genotype PCB-166 found to be better in terms of nutritional and antioxidant potential, and therefore, could fulfill the nutritional needs of the poor community. Further, processed millet flours could be utilized in the development of value added products. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05758-4.

30G needle aspiration - A modified technique of capsulorhexis in pediatric cataract with high intra-lenticular pressure.

This surgical technique describes a modification of the continuous curvilinear capsulorhexis (CCC) to achieve an adequate-sized capsulorhexis in pediatric cataracts with high intralenticular pressure. Performing CCC in pediatric cataracts is challenging, especially when the intralenticular pressure is high. This technique involves 30 G needle decompression of the lens to reduce positive intralenticular pressure and subsequent flattening of the anterior capsule. This minimizes the chances of extension of CCC without using any special equipment. This technique was used in two eyes of two patients (age 8 and 10 years) with unilateral developmental cataracts. Both surgeries were performed by a single surgeon (PKM). In both eyes, a well-centered CCC was achieved with no extension, and a posterior chamber intraocular lens (IOL) was placed in the capsular bag. Thus, our technique of 30 G needle aspiration could be extremely useful to achieve an adequately sized CCC in pediatric cataracts with high intralenticular pressure, especially for beginner surgeons.

Exploring Black and South Asian women's experiences of help-seeking and engagement in perinatal mental health services in the UK.

Background and aims: In the United Kingdom (UK), Black and South Asian women are less likely than White British women to access support from perinatal mental health services, despite experiencing similar, or higher, levels of distress. This inequality needs to be understood and remedied. The aim of this study was to answer two questions: how do Black and South Asian women experience (1) access to perinatal mental health services and (2) care received from perinatal mental health services? Method: Semi-structured interviews were conducted with Black and South Asian women (n = 37), including four women who were interviewed with an interpreter. Interviews were recorded and transcribed line-by-line. Data were analyzed using framework analysis, by an ethnically diverse multidisciplinary team of clinicians, researchers and people with lived experience of perinatal mental illness. Results: Participants described a complex interplay of factors that impacted on seeking, and receiving help, and benefiting from services. Four themes emerged that captured the highly varied experiences of individuals: (1) Self-identity, social expectations and different attributions of distress deter help-seeking; (2) Hidden and disorganized services impede getting support; (3) The role of curiosity, kindness and flexibility in making women feel heard, accepted and supported by clinicians; (4) A shared cultural background may support or hinder trust and rapport. Conclusion: Women described a wide range of experiences and a complex interplay of factors impacting access to, and experience of, services. Women described services as giving them strength and also leaving them disappointed and confused about where to get help. The main barriers to access were attributions related to mental distress, stigma, mistrust and lack of visibility of services, and organizational gaps in the referral process. These findings describe that many women feel heard, and supported by services, reporting that services provide a high quality of care that was inclusive of diverse experiences and understandings of mental health problems. Transparency around what PMHS are, and what support is available would improve the accessibility of PMHS.

Histopathological Predictors of Microsatellite Instability in Colorectal Cancer-a Tertiary Care Center Experience.

Microsatellite instability (MSI) has a therapeutic and prognostic implication in colorectal carcinomas (CRCs). It can be detected either by immunohistochemistry (IHC) or molecular studies. In developing countries, a significant proportion of the patients experience financial constraints limiting the utilization of healthcare facilities. We aimed to identify the possible clinicopathological variables which can be used as predictors of microsatellite instability in such patients. CRC cases received for MSI detection by IHC (for 1 and 1/2 years) were included. A panel of four IHC markers (anti-MLH1, anti-PMS2, anti-MSH2, and anti-MSH6) was used. Confirmation by the molecular study was recommended in all the IHC-proven MSI cases. Various clinicopathological parameters were evaluated as predictors of MSI. Microsatellite instability was detected in 40.6% (30/74) cases with MLH1 and PMS2 dual loss in 27% cases, MSH2 and MSH6 dual loss in 6.8%, loss of all four MMR proteins in 2.7%, and isolated PMS2 loss in 4.1%. MSI-H expression was shown by 36.5% cases with only 4.1% cases showing MSI-L expression. The age cut-off value to differentiate both the study groups (MSI vs MSS) was 63 years with a sensitivity of 47.7% and specificity of 86.7%. ROC curve showed an area under the curve of 0.65 (95% CI, 0.515-0.776; p-value = 0.03). On univariate analysis, age < 63 years, colon site, and absence of nodal metastasis were significantly higher in the MSI group. However, on multivariate analysis, only the age < 63 years was found to be significantly higher in the MSI group. Confirmation was molecular study could only be obtained in 12 cases and was completely concordant with MSI detection by IHC. MSI detection can be performed either by IHC or by molecular study. In this study, no histological parameter appeared to be the independent predictor of MSI status. The age < 63 years might predict the microsatellite instability, yet larger studies are needed for its validation. Thus, we recommend that IHC testing should be performed in all CRC cases.

Effect of herbicide stress on synchronization of carbon and nitrogen metabolism in lentil (Lens culinaris Medik.).

Weed invasion causes significant yield losses in lentil. Imazethapyr (IM), a broad-spectrum herbicide inhibits the biosynthesis of branched chain amino acids necessary for plant growth. Plant growth depends upon translocation of photo-assimilates and their partitioning regulated by carbon and nitrogen metabolism. This study aimed to investigate the impact of imazethapyr spray on carbon and nitrogen metabolism in tolerant (LL1397 and LL1612) and susceptible (FLIP2004-7L and PL07) lentil genotypes during vegetative and reproductive development. Significantly higher activities of invertases and sucrose synthase (cleavage) in leaves and in podwall and seeds during early phase of development in tolerant genotypes were observed as compared to susceptible genotypes under herbicide stress that might be responsible for providing hexoses required for their growth. Activities of sucrose synthesizing enzymes, sucrose phosphate synthase and sucrose synthase (synthesis) increased significantly in podwalls and seeds of LL1397 and LL1612 genotypes during later phase of development towards maturity while the activities decreased in FLIP2004-7L and PL07 genotypes under herbicide stress. Activities of nitrate and nitrite reductase, glutamine 2-oxoglutarate aminotransferase, glutamine synthetase and glutamate dehydrogenase were increased in leaves, podwalls and seeds of LL1397 and LL1612 under herbicide stress. A proper synchronization of carbon and nitrogen metabolism in tolerant lentil genotypes during vegetative and reproductive phase might be one of the mechanisms for their recovery from herbicide stress. This first ever comprehensive information will provide a basis for future studies on the molecular mechanism of source sink relationship in lentil under herbicide stress and will be utilized in breeding programmes.

Recent Patents and Potential Applications of Homogenisation Techniques in Drug Delivery Systems.

BACKGROUND: The term homogenise means "to force or provide coalesce". Homogenisation is a process to attain homogenous particle size. The objective of the homogenisation process is to use fluid force to split the fragments or tiny particles contained in the fluids into very small dimensions and form a sustainable dispersion suitable for further production. METHODS: The databases were collected through Scopus, google patent, science web, google scholar, PubMed on the concept of homogenisation. The data obtained were systematically investigated. RESULTS: The present study focus on the use of the homogenisation in drug delivery system. The aim of homogenisation process is to achieve the particle size in micro-and nano- range as it affects the different parameters in the formulation and biopharmaceutical profile of the drug. The particle size reduction plays a key role in influencing drug dissolution and absorption. The reduced particle size enhances the stability and therapeutic efficacy of the drug. Homogenization technology ensures to achieve effective, clinically efficient and targeted drug delivery with the minimal side effect. CONCLUSION: Homogenization technology has been shown to be an efficient and easy method of size reduction to increase solubility and bioavailability, stability of drug carriers. This article gives an overview of the process attributes affecting the homogenization process, the patenting of homogeniser types, design, the geometry of valves and nozzles and its role in drug delivery.

The effect of axillary crutch length on upper limb kinematics during swing-through gait.

BACKGROUND: Axillary crutches are commonly used in rehabilitation. Inappropriately fit crutches may result in upper limb pain or injury. OBJECTIVE: To investigate the effects of axillary crutch length on upper limb kinematics to better understand potential injury mechanisms. It was hypothesized that crutches that were longer or shorter than standard-fit crutches would alter upper limb kinematics. DESIGN: Cross-sectional. SETTING: Gait laboratory. PARTICIPANTS: Fifteen healthy males with no prior crutch experience. INTERVENTIONS: Participants were fit with axillary crutches using standardized methods, as well as with crutches that were 5 cm longer and 5 cm shorter. Participants performed swing-through gait (1.20 ± 0.07 ms-1 ) with all crutch lengths in randomized order. Kinematics were recorded using an optical motion-tracking system and joint angles for the scapula, shoulder, elbow, and wrist were computed. MAIN OUTCOME MEASURES: The effects of crutch length on joint range of motion (ROM) and joint angles at initial crutch contact were analyzed using multivariate analysis (Hotelling's T2 ; α = .025) and simultaneous confidence intervals (CI). RESULTS: The long-standard crutch fit comparison showed effects across all joints (ROM p = .009; initial contact p < .001). Longer crutches resulted in greater scapular upward rotation (mean difference [95% CI] ROM: 1.0 [-0.2 to 2.2]; initial contact: -2.7 [-4.4, -1.1]) and shoulder abduction (ROM: 0.8 [-0.1 to 1.8]; initial contact: -1.9 [-4.1 to 0.3]). Crutch length also had effects across all joints for the short-standard fit comparison (ROM p = .004; initial contact p = .016). Shorter crutches resulted in greater scapula downward rotation (2.2 [-0.4 to 4.8]) and greater shoulder adduction (2.5 [-0.6 to 5.6]) at initial contact. Shorter crutches also reduced shoulder flexion/extension ROM (-2.5 [-4.4 to -0.6]). CONCLUSIONS: Altered crutch length results in scapular and shoulder kinematic deviations that may present risk factors for upper limb injury with crutch-walking. This may underline the importance of appropriate device fitting to reduce injury risk in crutch users.

Chronic groin pain following inguinal hernia repair in the laparoscopic era: Systematic review and meta-analysis.

BACKGROUND: The impact of laparoscopic inguinal hernia repair (IHR) on chronic groin pain (CGP) prevalence, risk and daily activities compared to open IHR is still unclear. METHODS: A meta-analysis of randomised controlled trials comparing CGP rates in laparoscopic and open IHR was performed. RESULTS: 22 trials were included. CGP prevalence decreases significantly 1-2 years post-op and reaches rates as low as 4.69% (laparoscopic) and 6.91% (open) at >5 years. There is a significantly lower risk of CGP following totally extraperitoneal (TEP) than open mesh repair at all follow-up periods (p < 0.05) except for >5 years (p = 0.32). The same trend is not seen when compared to open non-mesh repair or for transabdominal pre-peritoneal repair (TAPP). There is no difference between techniques when CGP is described as moderate and/or affecting daily activities (p = 0.08). CONCLUSION: CGP rates continue to decrease at >5 years follow up. TEP consistently results in a reduction in CGP rates compared to open mesh repair however, this is not functionally significant.

'He or she maybe doesn't know there is such a thing as a review': A qualitative investigation exploring barriers and facilitators to accessing medication reviews from the perspective of people from ethnic minority communities.

INTRODUCTION: Regular reviews of medications, including prescription reviews and adherence reviews, are vital to support pharmacological effectiveness and optimize health outcomes for patients. Despite being more likely to report a long-term illness that requires medication when compared to their white counterparts, individuals from ethnic minority communities are less likely to engage with regular medication reviews, with inequalities negatively affecting their access. It is important to understand what barriers may exist that impact the access of those from ethnic minority communities and to identify measures that may act to facilitate improved service accessibility for these groups. METHODS: Semi-structured interviews were conducted between June and August 2021 using the following formats as permitted by governmental COVID-19 restrictions: in person, over the telephone or via video call. Perspectives on service accessibility and any associated barriers and facilitators were discussed. Interviews were audio-recorded and transcribed verbatim. Reflexive thematic analysis enabled the development of themes. QSR NVivo (Version 12) facilitated data management. Ethical approval was obtained from the Health Research Authority (ref: 21/HRA/1426). RESULTS: In total 20 participants from ethnic minority communities were interviewed; these participants included 16 UK citizens, 2 refugees and 2 asylum seekers, and represented a total of 5 different ethnic groups. Three themes were developed from the data regarding the perceived barriers and facilitators affecting access to medication reviews and identified approaches to improve the accessibility of such services for ethnic minority patients. These centred on (1) building knowledge and understanding about medication reviews; (2) delivering medication review services; and (3) appreciating the lived experience of patients. CONCLUSION: The results of this study have important implications for addressing inequalities that affect ethnic minority communities. Involving patients and practitioners to work collaboratively in coproduction approaches could enable better design, implementation and delivery of accessible medication review services that are culturally competent. PATIENT OR PUBLIC CONTRIBUTION: The National Institute for Health Research Applied Research Collaboration and Patient and Public Involvement and Engagement group at Newcastle University supported the study design and conceptualization. Seven patient champions inputted to ensure that the research was conducted, and the findings were reported, with cultural sensitivity.

In Silico transcriptional analysis of asymptomatic and severe COVID-19 patients reveals the susceptibility of severe patients to other comorbidities and non-viral pathological conditions

COVID-19 is a severe respiratory disease caused by SARS-CoV-2, a novel human coronavirus. The host response to SARS-CoV-2 infection is not clearly understood. Patients infected with SARS-CoV-2 exhibit heterogeneous intensity of symptoms, i.e., asymptomatic, mild, and severe. Moreover, effects on organs also vary from person to person. These heterogeneous responses pose pragmatic hurdles for implementing appropriate therapy and management of COVID-19 patients. Post-COVID complications pose another major challenge in managing the health of these patients. Thus, understanding the impact of disease severity at the molecular level is vital to delineate the precise host response and management. In the current study, we performed a comprehensive transcriptomics analysis of publicly available seven asymptomatic and eight severe COVID-19 patients. Exploratory data analysis using Principal Component Analysis (PCA) showed the distinct clusters of asymptomatic and severe patients. Subsequently, the differential gene expression analysis using DESeq2 identified 1,224 significantly upregulated genes (logFC>= 1.5, p-adjusted value <0.05) and 268 significantly downregulated genes (logFC<= -1.5, p-adjusted value <0.05) in severe samples in comparison to asymptomatic samples. Eventually, Gene Set Enrichment Analysis (GSEA) of upregulated genes revealed significant enrichment of terms, i.e., anti-viral and anti-inflammatory pathways, secondary infections, Iron homeostasis, anemia, cardiac-related, etc. Gene set enrichment analysis of downregulated genes indicates lipid metabolism, adaptive immune response, translation, recurrent respiratory infections, heme-biosynthetic pathways, etc. In summary, severe COVID-19 patients are more susceptible to other health issues/concerns, non-viral pathogenic infections, atherosclerosis, autoinflammatory diseases, anemia, male infertility, etc. And eventually, these findings provide insight into the precise therapeutic management of severe COVID-19 patients and efficient disease management.

Methylglyoxal detoxification pathway - Explored first time for imazethapyr tolerance in lentil (Lens culinaris L.).

Lentil is an important pulses crop but it's short stature and slow growth rate make it vulnerable to weed competition, limiting crop productivity. There is need to identify herbicide tolerant genotypes and their tolerance mechanism. The present investigation was conducted to understand the effect of imazethapyr (IM) treatment on accumulation of methylglyoxal (MG) and its detoxification mechanism in IM-tolerant (LL1397 and LL1612) susceptible (FLIP2004-7L and PL07) genotypes sown under control (weed free), weedy check (weeds were growing with crop) and sprayed with imazethapyr. The enzymes of glyoxalase pathway (glyoxalase I, II and III) and non glyoxalase pathway (methylglyoxal reductase), lactate dehydrogenase (LDH), glutathione content, gamma-glutamyl-cysteine synthetase (γ-GCS) were estimated in lentil genotypes at different days after spray. Higher activities of glyoxalase I, II and III and MGR along with the increased glutathione content (GSH) content in LL1397 and LL1612 under IM treatment as compared to FLIP2004-7L and PL07 might be responsible for lowering MG accumulation and increasing lactate content, which is end product of these pathways. Enhanced LDH activity in LL1397 and LL1612 might be responsible for energy production via TCA cycle that might be responsible for growth and recovery of tolerant genotypes after IM treatment. Higher γ-GCS activity in tolerant genotypes led to increased glutathione content required for glyoxalase pathway. However, decreased activities of glyoxalase enzymes and MGR in susceptible genotypes result in MG accumulation which limit plant growth. This is the first ever study elucidating the role of MG detoxification pathway conferring IM tolerance in lentil.