Genome-wide identification, characterization, and expression analysis unveil the roles of pseudouridine synthase (PUS) family proteins in rice development and stress response.

Pseudouridylation, the conversion of uridine (U) to pseudouridine (Ñ°), is one of the most prevalent and evolutionary conserved RNA modifications, which is catalyzed by pseudouridine synthase (PUS) enzymes. Ñ°s play a crucial epitranscriptomic role by regulating attributes of cellular RNAs across diverse organisms. However, the precise biological functions of PUSs in plants remain largely elusive. In this study, we identified and characterized 21 members in the rice PUS family which were categorized into six distinct subfamilies, with RluA and TruA emerging as the most extensive. A comprehensive analysis of domain structures, motifs, and homology modeling revealed that OsPUSs possess all canonical features of true PUS proteins, essential for substrate recognition and catalysis. The exploration of OsPUS promoters revealed presence of cis-acting regulatory elements associated with hormone and abiotic stress responses. Expression analysis of OsPUS genes showed differential expression at developmental stages and under stress conditions. Notably, OsTruB3 displayed high expression in salt, heat, and drought stresses. Several OsRluA members showed induction in heat stress, while a significant decline in expression was observed for various OsTruA members in drought and salinity. Furthermore, miRNAs predicted to target OsPUSs were themselves responsive to variable stresses, adding an additional layer of regulatory complexity of OsPUSs. Study of protein-protein interaction networks provided substantial support for the potential regulatory role of OsPUSs in numerous cellular and stress response pathways. Conclusively, our study provides functional insights into the OsPUS family, contributing to a better understanding of their crucial roles in shaping the development and stress adaptation in rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01396-4.

Sub-chronic and chronic toxicity evaluation of 7-methylxanthine: a new molecule for the treatment of myopia.

Myopia (nearsightedness) is a vision disorder with a blurring of far objects, affect millions worldwide. 7-methylxanthine (7-MX) is a molecule that is presently under clinical investigation for the treatment of myopia. In the present study, we have investigated sub-chronic and chronic toxicity of 7-MX in comparison to other clinically used methylxanthines i.e., caffeine and theobromine as per OECD guidelines 408 and 452. 7-MX was administered orally for 90 days at three different doses of 250, 500, and 1000 mg/kg for sub-chronic toxicity evaluation, and at a limit dose of 1000 mg/kg in 180 days chronic toxicity evaluation in rats. In sub-chronic treatment, 7-MX showed no mortality and signs for toxicity in any group, whereas 10% and 40% mortality with signs for toxicity were observed in caffeine and theobromine treated groups, respectively. A similar, safety profile was observed with 7-MX in 180 days of chronic toxicity study. Further, to confirm any morphological changes in organs; ultrasound and X-rays analysis were performed and no changes in the size of organs, cyst formation, fluid retention, or crystal formation was observed. Thus, the repeated dose study of 7-MX for 180 days may augment the possibility of using 7-MX clinically for the safe and effective treatment of myopia.

Pre-clinical and cellular toxicity evaluation of 7-methylxanthine: an investigational drug for the treatment of myopia.

The present study entails the toxicity evaluation of 7-methyl xanthine (7-MX), first of its kind molecule found effective in phase II clinical trials for the treatment of myopia, in comparison to other clinically used xanthines i.e., caffeine and theobromine. For acute toxicity evaluation, 7-MX was administered orally in two rodent species (rat and mice) at the doses of 300 mg/kg and 2000 mg/kg and for repeated dose 28-d oral toxicity, at 250, 500, and 1000 mg/kg in rats. Further, cellular toxicity was evaluated in normal breast epithelial (fR2), rat brain C6 glioma (C6 glioma) and human colorectal (Caco-2) cell lines. Also, the cell uptake assay to determine the intestinal permeability of drug was performed in Caco-2 cells. In acute toxicity, 7-MX treatment showed no mortality and toxicity, whereas 66.6% (mice) and 33.3% (rat) mortality was observed in both caffeine and theobromine treatment groups. In repeated dose 28-d oral toxicity, 7-MX treatment was found to have no-observed-adverse-effect level up to the dose of 1000 mg/kg in the present study conducted as per OECD guidelines 407. Also, very high IC50 value of 305.5 and 721 µg/mL was observed for 7-MX in fR2 and C6 glioma cells, respectively. In Caco-2 cells, linear bioavailability and high % cell viability was observed. Thus, 7-MX may be classified as Globally Harmonized System (GHS) category 5 drug with LD50 >2000-5000 mg/kg. Also, the repeated dose 28-d oral toxicity study demonstrated 7-MX to be nontoxic in nature, with cell line toxicity results further endorsing its nontoxic nature.

Myopia, its prevalence, current therapeutic strategy and recent developments: A Review.

Myopia is a widespread and complex refractive error in which a person's ability to see distant objects clearly is impaired. Its prevalence rate is increasing worldwide, and as per WHO, it is projected to increase from 22% in 2000 to 52% by 2050. It is more prevalent in developed, industrial areas and affects individuals of all ages. There are a number of treatments available for the control of myopia, such as glasses, contact lenses, laser surgery, and pharmaceuticals agents. However, these treatments are less beneficial and have significant side effects. A novel molecule, 7-methylxanthine (7-MX), has been found to be a highly beneficial alternate in the treatment of myopia and excessive eye elongation. Many preclinical and clinical studies showed that 7-MX is effective for the treatment of myopia and is presently under phase II of clinical investigation. We have also investigated preclinical toxicity studies such as acute, sub-acute, sub-chronic, and chronic on rats. In these studies, 7-MX was found to be non-toxic as compared to other reported anti-myopic agents. Moreover, as an ideal drug, 7-MX is observed to have no or low toxicity, brain permeability, non-allergic, higher oral administration efficacy, and low treatment costs and thus qualifies for the long-term treatment of myopia. This review article on 7-MX as an alternative to myopia treatment will highlight recent findings from well-designed preclinical and clinical trials and propose a potential future therapy.

An in silico comparative dosimetric study of postmastectomy locoregional irradiation using intensity-modulated vs 3-dimensional conventional radiotherapy.

An in silico dosimetric evaluation of intensity-modulated radiation therapy (IMRT) vs 3-dimensional conventional radiation therapy (3D-CRT) treatment plans in postmastectomy radiation therapy (PMRT) to the chest wall and regional lymphatics was conducted. Twenty-five consecutive patients with breast cancer referred for locoregional PMRT, stages T2-4 with N1-3, were planned to receive 50 Gy in 25 fractions with IMRT. Additionally, a 3D-CRT plan was generated using identical contours for the clinical target volumes (CTV), planning target volumes (PTV), and organs at risk (OAR). Treatment plans were assessed using dose-volume histogram (DVH) parameters of D98, D95, D50, D2, and homogeneity index for individual CTVs and PTVs. OARs evaluated were ipsilateral and contralateral lungs, heart, spinal cord, and opposite breast. Most DVH parameters pertaining to CTVs and PTVs significantly favored IMRT. V20 for ipsilateral and contralateral lungs, D33 of heart and maximum dose to spinal cord favored IMRT (all p < 0.001). The mean dose to the opposite breast was significantly lesser with 3D-CRT (5.8 ± 1.8 Gy vs 2.0 ± 1.0 Gy, p < 0.001). Thus, except for the mean dose to the opposite breast, the compliance to DVH constraints applied to PTV and OARs were significantly better with IMRT. At a median follow-up of 76 months (7-91), none had locoregional failure or pulmonary or cardiac morbidity. For PMRT, requiring comprehensive irradiation to both chest wall and regional lymphatics, IMRT offers superior dosimetric advantages over 3D-CRT. This was also corroborated by long-term outcomes in these patients treated with IMRT.

The use of adaptive intensity-modulated radiotherapy in the treatment of small-cell carcinoma lung refractory to chemotherapy in a patient with preexisting interstitial lung disease.

This is a case report of a 60-year-old diabetic, hypertensive male with a good performance status and a history of bilateral interstitial lung disease with a left upper lobe lung mass diagnosed to be a Stage IIB mixed small-cell/squamous cell carcinoma which was refractory to carboplatin- and etoposide-based chemotherapy. The patient was then taken up for adaptive intensity-modulated radiotherapy with tighter margin under image guidance with a mid-treatment replanning done at 25#. Acute toxicities were assessed weekly and showed no Grade 3 or more reactions. Pulmonary function test showed no detrimental changes during or after radiation. Response assessment at 12 and 20 weeks showed a partial response with decrease in metabolic activity on serial scans.

Dapsone induced acute photosensitivity dermatitis; a case report and review of literature.

Dapsone is one of the main constituents of anti-leprosy treatment and has been in use for various dermatological and non-dermatological indications since the 1940s. Dapsone-induced photosensitivity is a rare complication. Only 11 cases seem to have been reported in the literature. We report a case of dapsone-induced photosensitivity in an Indian patient with leprosy, and briefly review the literature. Dapsone (diaminodiphenyl sulphone or DDS) is the most commonly used anti-leprosy drug since the 1940s. Apart from leprosy, it is used for various other infectious and non- infectious dermatoses as well as for prevention of Pneumocystis carinii pneumonia in HIV infected patients. It is one of the main constituents of multidrug therapy (MDT) in leprosy by virtue of its anti-mycobacterial properties. It acts by interference with folate metabolism. Because of its inhibitory effect in neutrophil chemotaxis and neutrophilic oxygen burst, it acts as a potent anti-inflammatory agent. Documented cutaneous adverse effects of dapsone include generalised maculopapular rash, exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, erythema nodosum, pustular and acneiform skin eruptions. Photosensitivity dermatitis is a very rare side-effect of dapsone and to the best of our knowledge, only 11 cases have been reported in the literature to date.

Dosimetric Comparison of Pencil-Beam Scanning and Photon-Based Radiation Therapy as a Boost in Carcinoma of Cervix.

PURPOSE: Brachytherapy is essential for local treatment in cervical carcinoma, but some patients are not suitable for it. Presently, for these patients, the authors prefer a boost by using intensity-modulated radiation therapy (IMRT). The authors evaluated the dosimetric comparison of proton-modulated radiation therapy versus IMRT and volumetric-modulated arc therapy (VMAT) as a boost to know whether protons can replace photons. PATIENTS AND METHODS: Five patients who received external beam radiation therapy to the pelvis by IMRT were reviewed. Three different plans were made, including pencil beam scanning (PBS), IMRT, and VMAT. The prescribed planning target volume (PTV) was 20 Gy in 4 fractions. The dose to 95% PTV (D95%), the conformity index, and the homogeneity index were evaluated for PTV. The Dmax, D2cc, and Dmean were evaluated for organs at risk along with the integral dose of normal tissue and organs at risk. RESULTS: The PTV coverage was optimal and homogeneous with modulated protons and photons. For PBS, coverage D95% was 20.01 ± 0.02 Gy (IMRT, 20.08 ± 0.06 Gy; VMAT, 20.1 ± 0.04 Gy). For the organs at risk, Dmax of the bladder for PBS was 21.05 ± 0.05 Gy (IMRT, 20.8 ± 0.21 Gy; VMAT, 21.65 ± 0.41 Gy) while the Dmax for the rectum for PBS was 21.04 ± 0.03 Gy (IMRT, 20.81 ± 0.12 Gy; VMAT, 21.66 ± 0.38 Gy). Integral dose to normal tissues in PBS was 14.17 ± 2.65 Gy (IMRT, 25.29 ± 6.35 Gy; VMAT, 25.24 ± 6.24 Gy). CONCLUSIONS: Compared with photons, modulated protons provide comparable conformal plans. However, PBS reduces the integral dose to critical structures significantly compared with IMRT and VMAT. Although PBS may be a better alternative for such cases, further research is required to substantiate such findings.

Gambling control self-efficacy as a mediator of the effects of low emotional intelligence on problem gambling.

This study investigated whether lower emotional intelligence would be related to less self-efficacy to control gambling and more problem gambling and whether gambling self-efficacy would mediate the relationship between emotional intelligence and problem gambling. A total of 117 participants, including 49 women and 68 men, with an average age of 39.93 (SD = 13.87), completed an emotional intelligence inventory, a gambling control self-efficacy scale, and a measure of problem gambling. Lower emotional intelligence was related to lower gambling self-efficacy and more problem gambling. Gambling control self-efficacy partially mediated the relationship between emotional intelligence and problem gambling.

Dosimetric impact of setup errors in head and neck cancer patients treated by image-guided radiotherapy.

To assess and analyze the impact of setup uncertainties on target volume coverage and doses to organs at risk (OAR) in head and neck cancer (HNC) patients treated by image-guided radiotherapy (IGRT). Translational setup errors in 25 HNC patients were observed by kilovoltage cone beam computed tomography (kV CBCT). Two plans were generated. Plan one - the original plan which was the initially optimized and approved plan of the patient. All patients were treated according to their respective approved plans at a defined isocenter. Plan two - the plan sum which was the sum of all plans recalculated at a different isocenter according to setup errors in x, y, and z-direction. Plan sum was created to evaluate doses that would have been received by planning target volume (PTV) and OARs if setup errors were not corrected. These 2 plans were analyzed and compared in terms of target volume coverage and doses to OARs. A total 503 kV CBCT images were acquired for evaluation of setup errors in 25 HNC patients. The systematic (mean) and random errors (standard deviation) combined for 25 patients in x, y, and z directions were 0.15 cm, 0.21 cm, and 0.19 cm and 0.09 cm, 0.12 cm, and 0.09 cm, respectively. The study showed that there was a significant difference in PTV coverage between 2 plans. The doses to various OARs showed a nonsignificant increase in the plan sum. The correction of translational setup errors is essential for IGRT treatment in terms of delivery of planned optimal doses to target volume.

Augmented primary humoral immune response and decreased cell-mediated immunity by Murraya koenigii in rats.

BACKGROUND: Murraya koenigii (Rutaceae) (curry patta: Hindi) of the family Rutaceae is used in the traditional Indian system of medicine for its immunomodulatory properties. The essential oil of the leaves of M. koenigii possesses antimicrobial, antifungal, and pesticidal activities and is used for the treatment of amebiasis, diabetes, and hepatitis. The present study was performed to evaluate the effect of M. koenigii on humoral and cell-mediated immune responses in rats. METHODS: Aqueous extract of M. koenigii leaves was administered orally in a dose of 350 mg/kg. Cell-mediated immunity was assessed by measuring foot pad thickness following sensitization by injection of keyhole limpet hemocyanin and subsequent challenge by the same. Humoral immunity was assessed by measurement of hemagglutination titer to sheep red blood cells (SRBCs). RESULTS: In the humoral immune response, the administration of M. koenigii [350 mg/kg per os (p.o.)] from day 1 to day 7 after sensitization with SRBC on day 0 caused a significant increase in the primary anti-SRBC titer. However, the secondary immune response was decreased significantly (p<0.05) as shown by a decrease in secondary anti-SRBC titer measured on day 11 following a booster dose of antigen on day 8. In the delayed-type hypersensitivity test, M. koenigii (350 mg/kg, p.o.), when administered for 14 days, produced a significant (p<0.05) decrease in foot pad thickness when compared with the control group. CONCLUSIONS: Thus, these results suggest that oral administration of M. koenigii augments primary humoral immune response and decreases cell-mediated immunity.

Hand eczema: correlation of morphologic patterns, atopy, contact sensitization and disease severity.

BACKGROUND: Hand eczema is a common distressing condition aggravated by a number of endogenous and exogenous factors. Various morphological forms of hand eczema have been described, but categorization into one of them is not always possible. AIMS: To study the morphological patterns of hand eczema, relationship of atopy with hand eczema, and the implications of contact sensitization with respect to severity and diagnosis of hand eczema. METHODS: Hundred consecutive patients of hand eczema attending the contact dermatitis clinic of the institute were recruited over a two year period from 2004-05. Objective assessment was done using hand eczema severity index (HECSI) and all the patients were patch tested using Indian standard series. RESULTS: Unspecified type of hand eczema with no definite morphologic picture was seen in 62% followed by pompholyx in 14%. Hand eczema severity was not found to be statistically associated with age, sex, and atopic status of the patient. Positive patch test to one or more allergen was present in 65% of patients. The most common allergens were potassium dichromate (25%), fragrance mix (16%), nickel sulphate (14%), and PPD (13%). There was no significant correlation between patch test positivity and hand eczema severity or atopic status of the patient. Among the morphological patterns pompholyx was strongly associated with an atopic status (P=0.004). CONCLUSIONS: Hand eczema was seen twice more commonly in men. Atopic and non-atopic patients of hand eczema had no difference in the severity of disease. Contact sensitivity to different allergens did not correlate with increased eczema severity.

Side Lab Diagnosis of Chromoblastomycosis.

A 35 year old male having erythematous and verrucous plaques and scars on his right lower limb, diagnosed as a case of chromoblastomycosis is described. The importance of close scrutiny of lesions for brownish- black dots and their direct microscopic exarmination in 10% KOH for the causative fungus is highlighted. The causative fungus was identified as Cladosporium carrionni.