Cadila Pharmaceuticals

Eucalyptus globulus is one of the most important medicinal plants known for its volatile oil content. It has several uses in respiratory disorders as well as cough and cold, due to the presence of certain triterpenoids. In the present work a simple, consistent, and robust densitometric HPTLC method was devised and validated for simultaneous estimation of four triterpenoids in E. globulus leaves and bark, namely ursolic acid, betulinic acid, oleanolic acid, and lupeol. Various extraction procedures, including maceration, ultra sonication, heat reflux, and Soxhlet, were utilized to produce optimal extraction conditions of four triterpenoids from the plant sources. Pet. ether: ethyl acetate: acetone (8:2:0.5v/v/v) was used as the mobile phase for the chromatographic separation. After derivatization, the measurement of four triterpenoid was done using densitometric reflection/absorption mode at 366nm. In the linear working concentration range of 0.25-1.25µg/spot, precise quantification of UA, BA, OA, and lupeol were done with good correlation (r2=0.9917, 0.9986, 0.9950 and 0.990, respectively). Soxhlet extraction method provided best extraction yield, selectivity, and efficiency for all four triterpenoids. By this method, the estimated amounts of UA, BA, and, OA in leaves were found to be 6.85±0.273, 2.443±0.076, and 5.3±0.615mg/g dry weight [DW] , respectively, but the highest content of lupeol was detected in bark (0.377±0.035mg/g DW). The present work can serve as an exhaustive standardization tool for E. globulus since four of its bioactive phytochemicals have been estimated simultaneously, as well as throw light on the best extraction method.

Desmocollin-3 (DSC3), a transmembrane glycoprotein is expressed in various cancers like squamous lung, head & neck, Cervical, Melanoma, bladder cancer etc. DSC3 is also a predictive biomarker for efficacy of Mycobacterium w (Mw) vaccine, a heat-killed suspension of a non-pathogenic mycobacterium. It induces a DSC3-specific cell-mediated (CD8+ T cells) immune response and considered to be a barrier for immune infiltrate. Efficacy of anti-PD1/PDl1 therapy depends on tumor infiltrating immune cells. Present study focuses on the key immune genes and their relationship with DSC3 gene. DSC3 and other genes encoding various immune functions (Table) were evaluated across 17 cancers using cBioPortal TCGA PAN CANCER data set. For correlation between DSC3 and other immune genes, samples with a positive Z score for DSC3 or upper quartile DSC3 (lower of two) were used. DSC3 expression in Squamous lung cancer, Cancer cervix, head & neck, melanoma, colorectal cancer, mesothelioma and adenocarcinoma stomach were found to have major impact with negative Z score for majority of CD8, M1, Th1, T exhaust, M2 and Th2 genes suggesting lower infiltration of immunosuppressive and immunostimulant immune cells. Following genes had negative Z scores in all seven cancers:1. CD8 group: CD8A, CD8B, GZMA, GZMB, GZMK, GZMM, PRF1, TBX12. M1 group: CCL15, CCL20, CCR7, CXCL10, FCGR1BP, CYBB, Il15, 1l15RA3. Th1 group: CXCR3, IL274. Texhast; BTLA, LAG3, PDCD1, SLAMF6, TIGIT 5. Th2: BATF, CXCR6, SOCS1 6. M2: CD163Similar finding of lower magnitude were also seen in bladder cancer, ovarian cancer, thyroid cancer, pancreatic cancer, adenocarcinoma lung, uterine cancer, testicular germ cell cancer, renal cancer, sarcoma, hepatocellular cancer. DSC3 expressing tumours are likely to have lower TIL (immunostimulant as well immunosuppressive) and may not be ideal candidate for check point inhibitors. Bakulesh M. Khamar, Sanjay V. Malhotra. Desmocollin3 and tumor immune infiltrate: A bioinformatics evaluation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7065.

Background: Vitamin D deficiency (VDD) is a common condition in India with prevalence in general population varying from 50-94%. VDD has been associated with increased susceptibility to a wide range of viral infections including COVID-19. It is associated with worse outcomes and greater morbidity and mortality in medical as well as surgical ICUs. The objective of the study was to evaluate the pharmacokinetic (PK)/pharmacodynamic (PD) of aqueous cholecalciferol injection in comparison with conventional oil-based injection in VDD healthy adult subjects. Methods: 24 eligible vitamin D deficient healthy adult males, fulfilling the inclusion/exclusion criteria, were enrolled in the study. Subjects received a single dose of either test (T) [Aqueous cholecalciferol injection 600K IU/2 mL] or reference (R) [Cholecalciferol 600K IU oil-based injection] intramuscularly. Various PK parameters (Cmax, AUC0-t, AUC0-∞ and Tmax) and PD parameters (concentration of cholecalciferol and 25(OH)D) were measured along with safety analysis. Results: A significantly higher concentration of cholecalciferol and 25(OH)D were observed with test product compared to reference (p<0.01) from 1-hour post-administration till end of the study. A statistically significant difference between test and reference product was observed for the calculated Cmax and Tmax for cholecalciferol and 25(OH)D (p<0.0001). All 12 (100%) subject in test arm achieved the normal level of 25(OH)D by 72 hr post-administration as compared to none in reference arm (p=0.0017). There were no serious adverse events (SAEs) or deaths reported during the study. Conclusions: This first in world, aqueous formulation of cholecalciferol injection was found to be superior in various PK/PD parameters as compared to conventional oil based injection, which resulted in rapid and sustained rise in serum 25(OH)D levels.

Background: Initial wave of COVID-19 created a massive health crisis everywhere including India due to a limited understanding of the disease pathology. Most physicians used sepsis as a prototype to manage COVID-19, as there are similarities. Heat-killed Mycobacterium w (Mw) (inj. sepsivac®) is a known immunomodulator approved for the treatment of gram-negative sepsis. Our purpose of this observation is to evaluate the safety and efficacy of Inj sepsivac in COVID-19 patients along with the standard of care. Methods: Total 49 patients data with reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed critically ill COVID-19 patients who were admitted at Velocity Hospital, Surat between May 4, 2021, and May 18, 2021 were evaluated. They were evaluated for vital parameters like pulse, blood pressure, respiratory rate and temperature as well as laboratory parameters like ALT, S IL-6, serum creatinine and CRP during three follow-up visits after the administration of Inj sepsivac. Further follow-up was done until the discharge/death of the patient. Results: There was a statistically significant reduction of mean CRP observed compared to the baseline value during all follow-up visits. The rest of the laboratory parameters as well as clinical assessment did not show any significant change as compared to baseline. Out of 49, two patients died (mortality rate; 4%). Inj. sepsivac was found to be well tolerated without any systemic side effects. Conclusions: The addition of Mw to the standard of care can improve laboratory parameters like CRP, without any safety concerns. These results should be further substantiated by larger randomised clinical trials.

This work presented the first report on designing, synthesizing of novel pyrazole-triazole-persulfonimide (7a-i) and pyrazole-triazole-aryl derivatives (8a-j) via click reaction using CuI catalyst and evaluated for their anti diabetic activity and DPP-4 inhibitory effect. Click reactions went smoothly with CuI catalyst in the presence of tridentate chelating ligands and produced copper-free target pyrazole-triazole-persulfonimide analogues in excellent yield at RT. The designed compounds were docked against DPP-4 enzyme and showed excellent interaction with active amino acids residue. Further, all novel pyrazole-triazole-persulfonimide and pyrazoletriazole derivatives were subjected to enzyme-based in vitro DPP-4 inhibitory activity. Based on the SAR study DPP-4 inhibitory capacity compounds 7f (9.52 nM) and 8h (4.54 nM) possessed the significant inhibition of DPP 4. Finally compounds 7f and 8h were evaluated for their in vivo anti-diabetic activity using STZ induced diabetic mice model, and 8h showed a significant diabetic control effect compared to the sitagliptin drug. These studies demonstrated that the novel pyrazole-triazole-persulfonimide and pyrazole-triazole-aryl derivatives might be used as the leading compounds to develop novel DPP-4 inhibitors as potential anti-diabetic agents.