Andrographolide protect against lipopolysacharides induced vascular endothelium dysfunction by abrogation of oxidative stress and chronic inflammation in Sprague-Dawley rats.

The development of heart disease involves interconnected factors such as oxidative stress, inflammation, and vascular dysfunction. Andrographolide (AG), known for its potent antioxidant and anti-inflammatory properties, has the potential to counteract lipopolysaccharides (LPS)-induced endothelial dysfunction by reducing oxidative stress and inflammation. Our research aimed to investigate the effects of AG on alleviating vascular endothelium dysfunction, oxidative stress, and inflammation in an experimental model induced by LPS. To create chronic vascular endothelium dysfunction, inflammation, and oxidative stress, rats received weekly injections of LPS via their tail vein over a 6-week period. The study evaluated the therapeutic effects of orally administered AG (50 mg/kg/day) on diseased conditions. We conducted aortic histology and measured nitric oxide (NO) thresholds, superoxide dismutase (SOD) activity, constitutive nitric oxide (cNOS) activity, and inducible nitric oxide (iNOS) levels, alongside several inflammatory biomarkers. To evaluate endothelial dysfunction, we assessed endothelium-dependent and endothelium-independent vasorelaxation in aortas through histopathological and various immunoassays examinations. Vascular Endothelial inflammatory activity was consequently enhanced in LPS groups animals when compared to normal control, also endothelial performance were dependently improved by AG therapy. IL-1ß and tumors necrosis factor levels in the aorta decreased in a dose-dependent manner after exogenous AG delivery to LPS-treated rats. However, in current research work aortic SOD activity, NO levels, and cNOS activity increased, whereas aortic malondialdehyde levels and iNOS activity decreased after the AG treatment. These findings suggest that long-term AG therapy could be considered as a potential therapy to avoid vascular endothelial dysfunction and major nonobstructive coronary artery disease.

5-Fluorouracil and Anti-EGFR antibody scaffold chitosan-stabilized Pickering emulsion: Formulations, physical characterization, in-vitro studies in NCL-H226 cells, and in-vivo investigations in Wistar rats for the augmented therapeutic effects against squamous cell carcinoma.

This research seeks to optimize a chitosan-stabilized Pickering emulsion (PE) containing 5-fluorouracil (5-FU) as a potential Squamous Cell Carcinoma therapy. The 5-Fluorouracil was also thoroughly analysed using UV spectrophotometry and RP-HPLC, demonstrating exceptional linearity, sensitivity, precision, and robustness. The techniques of characterization revealed Pickering emulsion (PE) morphology, solid-like gel properties, successful encapsulation, and promising anticancer effects. FTIR was used to validate the efficacy of encapsulation, and DSC was used to confirm the post-encapsulation drug stability. The 0.6 % chitosan-stabilized PE showed exceptional stability and drug loading efficiency. Anti-EGFR-5-FU-CS-PE gel was developed for sustained drug release in the treatment of Squamous Cell Carcinoma. Anti-EGFR-5-FU-CS-PE demonstrated potent anticancer effects in vitro, with a lower IC50 than 5-FU and 5-FU-CS-PE. Anti-EGFR-5-FU-PE Pickering emulsions based on chitosan were investigated for their rheological properties, cellular interactions, and therapeutic potential. Both emulsions and gel exhibited sustained in vitro drug release after successful encapsulation. Anti-EGFR-5-FU-CS-PE induced apoptosis, decreased mitochondrial membrane potential, and inhibited the migration of cancer cells. Wistar mice were tested for safety and tumour growth inhibition. All formulations exhibited exceptional six-month stability. Anti-EGFR-5-FU-CS-PE emerges as a viable therapeutic option, necessitating additional research.

A shift in focus towards precision oncology, driven by revolutionary nanodiagnostics; revealing mysterious pathways in colorectal carcinogenesis.

Multiple molecular mechanisms contribute to the development of colorectal cancer (CRC), with chromosomal instability (CIN) playing a significant role. CRC is influenced by mutations in several important genes, including APC, TP53, KRAS, PIK3CA, BRAF, and SMYD4. The three molecular subtypes of this disease are CIN, MSI-H, and CIMP (CpG-island phenotype). p53 dysfunction and aberrant Wnt signalling are common characteristics of CRC carcinogenesis. Despite advances in conventional therapy, metastatic CRC remains difficult to treat due to toxicity and resistance. Theranostics for cancer could significantly benefit from nanotechnology, as it would enable more targeted, individualised care with fewer side effects. Utilising functionalized nanoparticles has enabled MRI-guided gene therapy, magnetic hyperthermia, chemotherapy, immunotherapy, and photothermal/photodynamic therapy, thereby radically modifying the way cancer is treated. Active targeting using ligands or peptides on nanoparticles improves the delivery of drugs to cancer cells. Nanostructures such as drug peptide conjugates, chitosan nanoparticles, gold nanoparticles, carbon nanotubes, mesoporous silica-based nanoparticles, silver nanoparticles, hybrid lipid-polymer nanoparticles, iron oxide nanoparticles, and quantum dots may enable targeted drug delivery and enhanced therapeutic efficacy against CRC. Nanomedicines are presently being evaluated in clinical trials for the treatment of colorectal cancer, with the promise of more effective and individualised therapies. This article examines current nanomedicine patents for CRC, including the work of Delta-Fly, Merrimack, and Pfenning, Meaning & Partner, among others. In terms of future nanomedicine research and development, ligand production, particle size, and clearance are crucial factors. Lastly, the numerous nanostructures utilized in nanomedicine for targeted drug administration and diagnostics indicate optimistic prospects for enhancing CRC treatment. The successes of nanomedicine research and development for existing colon cancer treatments are also highlighted in this review.

Physicochemical characterization, in vitro and in vivo evaluation of chitosan/carrageenan encumbered with Imatinib mesylate-polysarcosine nanoparticles for sustained drug release and enhanced colorectal cancer targeted therapy.

The objective of this investigation was to fabricate nanoparticles consisting of Imatinib mesylate-poly sarcosine-loaded chitosan/carrageenan in order to attain prolonged drug release and efficacious therapy for colorectal cancer. The study involved the synthesis of nanoparticles through the utilisation of ionic complexation and nanoprecipitation techniques. The subsequent nanoparticles were subjected to an assessment of their physicochemical characteristics, anti-cancer efficacy using HCT116 cell line, and acute toxicity. The present study examined two distinct nanoparticle formulations, namely IMT-PSar-NPs and CS-CRG-IMT-NPs, with respect to their particle size, zeta potential, and morphology. Both formulations demonstrated satisfactory characteristics, as they displayed consistent and prolonged drug release for a duration of 24 h, with the highest level of release occurring at a pH of 5.5. The efficacy and safety of IMT-PSar-NPs and CS-CRG-IMT-PSar-NPs nanoparticles were evaluated through various tests including in vitro cytotoxicity, cellular uptake, apoptosis, scratch test, cell cycle analysis, MMP & ROS estimate, acute toxicity, and stability tests. The results suggest that these nanoparticles were well fabricated and have promising potential for in vivo applications. The prepared polysaccharide nanoparticles have great potential for active targeting and could potentially reduce dose-dependent toxicity in the treatment of colon cancer.

Dacarbazine-encapsulated solid lipid nanoparticles for skin cancer: physical characterization, stability, in-vivo activity, histopathology, and immunohistochemistry.

Background: This study examined the use of solid lipid nanoparticles (SLNs) to administer Dacarbazine (DTIC) to skin melanoma cells with minimal adverse effects. Melanoma is a tricky skin cancer to cure, and standard chemotherapy has many negative effects. Encapsulating DTIC in SLNs may allow the drug to target melanoma cells without harming healthy cells. The study developed and tested DTIC-loaded SLNs for skin melanoma treatment. Methods: This study encapsulated Dacarbazine (DTIC) in solid lipid nanoparticles (SLNs). SLNs with reversed micelles were produced utilizing specified ratios of the surfactant Kolliphor® P188 and phosphatidylcholine. To track SLN drug localisation, gold nanoparticles were conjugated to the DTIC. Nanoparticle size and form were examined using DLS and TEM. These approaches ensured SLNs had the correct size and shape for drug delivery. Significant findings: In the study, various parameters of the developed solid lipid nanoparticles (SLNs) were evaluated, including particle size, zeta potential, polydispersity index (PDI), entrapment efficacy, and cumulative drug permeation. The values for these parameters varied across the different formulations, with particle size ranging from 146 ± 4.71 nm to 715 ± 7.36 nm, zeta potential from -12.45 ± 2.78 mV to -30.78 ± 2.83 mV, PDI from 0.17 ± 0.013 to 0.51 ± 0.023, entrapment efficacy from 37.78 ± 2.78% to 87.45 ± 4.78%, and cumulative drug permeation from 117 ± 4.77 µg/cm2 to 275 ± 5.67 µg/cm2. To determine the optimal anti-cancer formulation, the DTIC-SLNs-8 nanoparticles were mixed with an optimized concentration of Gellan gum (0.01% w/v) and applied to DMBA-induced skin tumors in rats for six weeks, twice daily. Histopathology demonstrated that DTIC-SLNs-8-treated rats had less keratosis, inflammatory responses, and angiogenesis than free DTIC-treated rats. The development of SLNs may be a promising approach for melanoma treatment due to their improved drug retention over the skin. The optimised anti-cancer formulation DTIC-SLNs-8 showed improved efficacy with minimal side effects as compared to free DTIC.

The neuroprotective effect of ascorbic acid against imidacloprid-induced neurotoxicity and the role of HO-1 in mice.

Imidacloprid (IMI) is not only a neurotoxic agricultural pesticide but also a possible food contaminant. The aims of this study were to (1) explore the relationship between recurrent IMI administration and neuronal toxicity in mice and (2) evaluate the potential neuroprotective effect of ascorbic acid (AA), a substance with significant free radical scavenger and having property to block the inflammatory pathways. Mice were categorized as naïve controls (administered vehicles for 28 days); the IMI-treatment animal group (administered po 45-mg/kg body weight of IMI per day for 28 days); and the IMI + AA treatment animal group (administered the same IMI dose + 200 mg/kg of AA orally for 28 days). On day 28, memory losses were assessed using the Y-maze and novel target identification behavioral tests. Mice were sacrificed 24 h after the final IMI treatments, as well as hippocampus tissues, were utilized to determine histological assessments, oxidative stress biomarkers, and Heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression levels. The findings demonstrated that IMI-treated mice had substantial impairment of spatial and non-spatial memory functions, as well as reduced antioxidant enzyme and acetylcholinesterase activity. The AA neuroprotective action was achieved through the suppression of the HO-1 expression as well as the stimulation of Nrf2 expression in hippocampal tissues. In summary, recurrent IMI exposure causes oxidative stress and neurotoxicity in mice, and the administration of AA significantly reduces the IMI toxicity possibly by the activation of the HO-1/Nrf2 pathway.

Serratiopeptidase Attenuates Lipopolysaccharide-Induced Vascular Inflammation by Inhibiting the Expression of Monocyte Chemoattractant Protein-1.

Lipopolysaccharide (LPS) has potent pro-inflammatory properties and acts on many cell types including vascular endothelial cells. The secretion of the cytokines MCP-1 (CCL2), interleukins, and the elevation of oxidative stress by LPS-activated vascular endothelial cells contribute substantially to the pathogenesis of vascular inflammation. However, the mechanism involving LPS-induced MCP-1, interleukins, and oxidative stress together is not well demonstrated. Serratiopeptidase (SRP) has been widely used for its anti-inflammatory effects. In this research study, our intention is to establish a potential drug candidate for vascular inflammation in cardiovascular disorder conditions. We used BALB/c mice because this is the most successful model of vascular inflammation, suggested and validated by previous research findings. Our present investigation examined the involvement of SRP in vascular inflammation caused by lipopolysaccharides (LPSs) in a BALB/c mice model. We analyzed the inflammation and changes in the aorta by H&E staining. SOD, MDA, and GPx levels were determined as per the instructions of the kit protocols. ELISA was used to measure the levels of interleukins, whereas immunohistochemistry was carried out for the evaluation of MCP-1 expression. SRP treatment significantly suppressed vascular inflammation in BALB/c mice. Mechanistic studies demonstrated that SRP significantly inhibited the LPS-induced production of proinflammatory cytokines such as IL-2, IL-1, IL-6, and TNF-α in aortic tissue. Furthermore, it also inhibited LPS-induced oxidative stress in the aortas of mice, whereas the expression and activity of monocyte chemoattractant protein-1 (MCP-1) decreased after SRP treatment. In conclusion, SRP has the ability to reduce LPS-induced vascular inflammation and damage by modulating MCP-1.

Development of D-α-Tocopherol polyethylene glycol 1000 succinate fabricated nanostructural lipid carrier of sorafenib tosylate for metastatic colorectal targeting application: Stability, physical characterization, cytotoxicity, and apoptotic studies against SW48 cells PTEN.

The study aimed to create D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) nanostructured lipid carriers (NLC) of sorafenib tosylate (ST) as lymphatic delivery systems (LDDS) to fight Metastatic colorectal cancer. Initially, ST-SLN, ST-NLC, and ST-LNE were formulated considering oleic acid (OA), glycerol monolinoleate (GMO), glycerol monolinoleate (GML) as solid lipid and further characterised, and tested for stability. The most stable ST-NLC was fabricated with TPGS to produce ST-TPGS-NLC and evaluated by performing in vitro drug profiling, in vitro cytotoxicity, and apoptotic studies against human female colorectal adenocarcinoma cell lines (SW48 Cells PTEN). Stability studies on three lipidic nanoparticles (ST-SLN, ST-NLC, ST-LEN) showed particle size, polydispersity index, and zeta potential ranging from 165 nm to 298 nm, 0.125 to 0.288, and -31 mV to -16 mV. At 1600 minutes, more than 80% of ST-NLC1 was released, confirming the sustained release pattern of the formulation. ST-NLC and ST-TPGS-NLC have entrapment efficiencies above 50%. Pure ST's IC50 at 72 hr was 3.45 µg/mL, while 1.56 µg/mL was for ST-TPGS-NLC. The ST-TPGS-NLC reduced the number of livings SW48 Cells PTEN from 91% to 5%, compared to 75% to 8% of pure ST. The ST-TPGS-NLC is a promising LDDS for delivering ST for metastatic colorectal cancer.

Why Do People Live or Die? A Retrospective Study from a Crisis Intervention Clinic in North India.

Background: Suicide results from complex interactions of various risk factors-reasons for dying (RFD)-and protective factors-reasons for living (RFL). Suicide is not necessarily a wish to die but may be an appeal for help. We analyzed RFD and RFL in persons who had attempted suicide, through their clinical records at a Crisis Intervention Clinic (CIC). Methods: We retrospectively analyzed demographic and clinical data, and classified RFD and RFL, among patients with either ideas or attempt of suicide registered at our CIC (N = 83). Using two open-ended questions from the clinical history data, we derived their RFD or RFL; (n = 53) completed these questions regarding RFD-RFL. Results: In the total sample, males and females were equally represented and educated, but males were significantly older. Most common diagnosis was nonpsychotic mood disorder. Commonest mode of suicide attempt was hanging. Family conflict vs. family responsibility, hope vs. hopelessness, stressful life events, and negative cognitions about the self and the world were important RFD. RFL included feeling responsible, love for family and for self, hope, career success, and religious beliefs. Conclusion: RFD and RFL could both be grouped in similar categories related to family, career, hope, etc.

Psychometric properties of a screening tool for autism in the community-The Indian Autism Screening Questionnaire (IASQ).

INTRODUCTION: Currently available screening questionnaires for Autism spectrum disorders were tested in developed countries, but many require additional training and many are unsuitable for older individuals, thus reducing their utility in lower/ middle- income countries. We aimed to derive a simplified questionnaire that could be used to screen persons in India. METHODS: We have previously validated Indian Scale for Assessment of Autism (ISAA), that is now mandated for disability assessment by the Government of India. This detailed tool requires intensive training and it is time consuming. It was used to derive a new screening questionnaire: 1) items most frequently scored as positive by participants with autism in original ISAA validation study were modified for binary scoring following expert review. 2) In a new sample, clinically diagnosed individuals with/without autism were administered the screening tool and ISAA following written informed consent. Its psychometric properties were determined. RESULTS: A 10-item scale named Indian Autism Screening Questionnaire (IASQ) was prepared in Hindi and English. Thereafter 145 parents/caregivers of participants (autism, n = 90, other psychiatric disorders, n = 55) (ages 3-18), were administered IASQ and ISAA (parents/caregivers plus observation) by separate interviewers, blind to each other and to diagnosis. At a cutoff of 1, sensitivity was 99%, specificity 62%, Positive Predictive Value 81%, and Negative Predictive Value 95%. Test-retest reliability was r = 0.767 (CI = 0.62-0.86) and interrater reliability- Krippendorff"s-alpha was 0.872. The area under Receiver Operating Characteristic Curve (ROC) was 95%. There was a significant difference on IASQ-scores between participants with and without a clinical diagnosis of Autism (t = 14.57, p<0.0001). DISCUSSION: The IASQ is a simple, easy to use screening tool with satisfactory reliability and validity, that can be administered to caregivers in 15 minutes and provides information about DSM 5 criteria for autism. It may be applicable outside India, following additional adaptation, for community-based studies.

Protocol for Development of the Indian Autism Screening Questionnaire: The Screening Version of the Indian Scale for Assessment of Autism.

INTRODUCTION: Autism is included as a certifiable disability in the Indian Rights of Persons with Disability Act, 2016. The Indian Scale for Assessment of Autism (ISAA), developed by the Government of India and mandated for certifying disability, is a detailed instrument that needs trained mental health experts and takes time to administer. The current project was planned to develop a simple, easy to use screening tool based on the ISAA to identify possible cases in the community. METHODS: The project is planned in three phases. During the first phase, data collected during the development of the ISAA (N = 433/436 children with autism) will be used to identify questions answered as frequently, mostly, and always. During the second phase, the psychometric properties of the screening tool based on these items will be evaluated among research participants recruited from hospitals and special schools (n = 100). In the third phase, the screening questionnaire will be administered in the community (n = 500). RESULTS: The most frequently answered questions will be selected for inclusion in the proposed screening tool. The number of items in the screening tool will be kept as few as possible, with yes or no responses. DISCUSSION: Indian Autism Screening Questionnaire (IASQ) will be tested as a screening version of ISAA, which can be used by community health workers, teachers, or school counselors. The IASQ will not provide a diagnosis of autism. A positive screening result should be followed by a thorough assessment by a trained specialist. Analyzing the psychometric properties of the test can help ensure cost-effective screening of the community to identify autism.

Circular RNA Profiling by Illumina Sequencing via Template-Dependent Multiple Displacement Amplification.

Circular RNAs (circRNAs) are newly discovered incipient non-coding RNAs with potential roles in disease progression in living organisms. Significant reports, since their inception, highlight the abundance and putative functional roles of circRNAs in every organism checked for, like O. sativa, Arabidopsis, human, and mouse. CircRNA expression is generally less than their linear mRNA counterparts which fairly explains the competitive edge of canonical splicing over non-canonical splicing. However, existing methods may not be sensitive enough for the discovery of low-level expressed circRNAs. By combining template-dependent multiple displacement amplification (tdMDA), Illumina sequencing, and bioinformatics tools, we have developed an experimental protocol that is able to detect 1,875 novel and known circRNAs from O. sativa. The same method also revealed 9,242 putative circRNAs in less than 40 million reads for the first time from the Nicotiana benthamiana whose genome has not been fully annotated. Supported by the PCR-based validation and Sanger sequencing of selective circRNAs, our method represents a valuable tool in profiling circRNAs from the organisms with or without genome annotation.

Introduction of a pseudo demons force to enhance deformation range for robust reconstruction of super-resolution time-resolved 4DMRI.

PURPOSE: The purpose of this study was to enhance the deformation range of demons-based deformable image registration (DIR) for large respiration-induced organ motion in the reconstruction of time-resolved four-dimensional magnetic resonance imaging (TR-4DMRI) for multi-breath motion simulation. METHODS: A demons-based DIR algorithm was modified to enhance the deformation range for TR-4DMRI reconstruction using the super-resolution approach. A pseudo demons force was introduced to accelerate the coarse deformation in a multi-resolution (n = 3) DIR approach. The intensity gradient of a voxel was applied to its neighboring (5 × 5 × 5) voxels with a weight of Gaussian probability profile (σ = 1 voxel) to extend the demons force, especially on those voxels that have little intensity gradience but high-intensity difference. A digital 4DMRI phantom with 3-8 cm diaphragmatic motions was used for DIR comparison. Six volunteers were scanned with two high-resolution (highR: 2 × 2 × 2 mm3 ) breath-hold (BH) 3DMR images at full inhalation (BHI) and full exhalation (BHE) and low-resolution (lowR: 5 × 5 × 5 mm3 ) free-breathing (FB) 3DMR cine images (2 Hz) under an IRB-approved protocol. A cross-consistency check (CCC) (BHI→FB←BHE), with voxel intensity correlation (VIC) and inverse consistency error (ICE), was introduced for cross-verification of TR-4DMRI reconstruction. RESULTS: Using the digital phantom, the maximum deformable magnitude is doubled using the modified DIR from 3 to 6 cm at the diaphragm. In six human subjects, the first 15-iteration DIR using the pseudo force deforms 200 ± 150% more than the original force, and succeeds in all 12 cases, whereas the original demons-based DIR failed in 67% of tested cases. Using the pseudo force, high VIC (>0.9) and small ICE (1.6 ± 0.6 mm) values are observed for DIR of BHI&BHE, BHI→FB, and BHE→FB. The CCC identifies four questionable cases, in which two cases need further DIR refinement, without missing true negative. CONCLUSIONS: The introduction of a pseudo demons force enhances the largest deformation magnitude up to 6 cm. The cross-consistency check ensures the quality of TR-4DMRI reconstruction. Further investigation is ongoing to fully characterize TR-4DMRI for potential multi-breathing-cycle radiotherapy simulation.

A Pilot Study of Correlation between Intelligence Quotient, Social Quotient, and Ayurveda Parameters in Children.

BACKGROUND: Intelligence quotient (IQ) and social quotient (SQ) are comparable in predicting intelligence status. The latter is assessed whenever IQ testing is not possible. According to Ayurveda, Buddhi (intelligence) is affected by Prakriti (body constitution) which depends on the predominance of Tridosha and Triguna. There is a paucity of studies to examine their association. The study was designed to examine correlation among IQ, SQ, performance quotient (PQ) and maladaptive behaviour; and to find out their relationship with primary (Anubandhya) and secondary (Anubandha) doshas with intelligence in children with mild to moderate intellectual disability. METHODOLOGY: Children (n = 120) were recruited from outpatient department of a tertiary care hospital as part of a clinical trial of a novel Ayurveda formulation. Stanford Binet Scale, Vineland Social Maturity Scale, Seguin Form Board Test, and Maladaptive Behavior Schedule-II were administered. Ayurvedic parameters were assessed clinically by Ayurveda practitioner. Separate regression analyses were carried out to look for associations. RESULTS: IQ and SQ were positively correlated (P = 0.01). Maladaptive behavior and SQ were negatively correlated (0.05). SQ was associated with secondary dosha (P = 0.002) and stage of disease (Roga Kriyakala) (P = 0.015). IQ was also associated with secondary dosha (P = 0.008). CONCLUSION: SQ and IQ are positively correlated. The correlation of Anubandha (secondary) dosha was high on IQ and SQ.

Lingual versus buccal mucosa graft urethroplasty for anterior urethral stricture: a prospective comparative analysis.

OBJECTIVE: To compare lingual and buccal mucosa graft urethroplasty for anterior urethral stricture with respect to intraoperative, postoperative parameters and urethroplasty outcome. METHODS: From January 2011 to December 2011, a total of 30 patients with anterior urethral stricture whereas group 2 underwent dorsal onlay buccal mucosa graft urethroplasty. Patients were evaluated for postoperative, tongue protrusion, oral opening, and difficulty in speech and swallowing pain score. Surgical outcome was evaluated with pre- and postoperative work-up involving retrograde urethrogram, uroflow and urethroscopy. RESULTS: Mean age, stricture length and overall pain score were comparable in two groups. All the patients were mostly pain free by postoperative day 7. Group 1 patients had significant difficulty in speech and delayed return to normal diet as compared with group 2. The group 2 patients had a significant reduction in oral opening for the first week after surgery. In group 1, approximately 20% patients (with bilateral lingual grafts and stricture length >7 cm) complained of a change in speech character with restricted tongue movement in the long term, whereas there was no significant long-term morbidity in group 2. At mean follow up of 14.5 months, urethroplasty outcome was comparable in the two groups with one failure in group 1, and two failures in group 2. CONCLUSION: Lingual mucosa graft urethroplasty provides outcomes equivalent to those of buccal mucosa graft urethroplasty. Postoperative morbidity and long-term change in speech make it a second choice for strictures >7 cm, only for cases where buccal mucosa graft is unavailable.