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Fulltext Lymphatic Filariasis Presenting as a Swelling over the Upper Arm: A Case Report

Sharma GM, Bhardwaj AR, Relwani NR, Dubey S

Malays Orthop J, 2018 Mar;12(1):63-65.
PMID: 29725519 DOI: 10.5704/MOJ.1803.016

Filariasis continues to be one of the endemic problems worldwide with 40% of the cases in India. We report a case of lymphatic filariasis in a 32-year old female who presented with a non-tender swelling over left upper arm. Blood sample showed no eosinophilia while the FNAC was diagnostic of W. bancrofti. Patient responded well with oral diethylcarbamazine. High index of suspicion of filariasis is indicated when dealing with a swelling of unknown cause especially in filariasis endemic areas.
Fulltext Thigh Pain and Peri-Implant Fractures with the Use of Short Cephalo-medullary Nails: A Retrospective Study of 122 Patients

Dubey S, Iyer RD, Azam MQ, Sarkar B, Nongdamba H

Malays Orthop J, 2022 Nov;16(3):17-23.
PMID: 36589363 DOI: 10.5704/MOJ.2211.004

INTRODUCTION: To assess the incidence and causes of persistent thigh pain and peri-implant fractures after union in patients of intertrochanteric fractures treated with short cephalo-medullary nails.
MATERIALS AND METHODS: A retrospective observational study conducted at a Level 1 Trauma centre. A total of 122 patients of intertrochanteric fractures who were operated using short cephalo-medullary nails (170mm and 200mm lengths) between January 2018 to June 2019 were included in the study. Main outcomes measured were the incidence of thigh pain and peri-implant fractures.
RESULTS: Out of the 122 patients with a mean follow-up of 14.1 month, 12 patients had persistent thigh pain. Six patients had the helical blade protruding from the lateral cortex, two of them had distal tip of nail abutting on the anterior cortex and four cases had prominent proximal segment of nail which may explain the cause of their pain. Five of these patients had a combination of these findings. Two patients had pain for which no other obvious cause was found. There were no cases of peri-implant fractures in our study.
CONCLUSION: Thigh pain associated with the use of short cephalon-medullary nails is often unrelated to nail length and can be prevented by using proper surgical technique. There seems to be no association between the use of short nails and peri-implant fractures.
Emerging innovations in nano-enabled therapy against age-related macular degeneration: A paradigm shift

Kumar Dubey S, Pradhan R, Hejmady S, Singhvi G, Choudhury H, Gorain B, et al.

Int J Pharm, 2021 May 01;600:120499.
PMID: 33753164 DOI: 10.1016/j.ijpharm.2021.120499

Age-related macular degeneration (AMD), a degenerative eye disease, is the major cause of irreversible loss of vision among individuals aged 50 and older. Both genetic and environmental factors are responsible for the progressive damage to central vision. It is a multifactorial retinal disease with features such as drusen, hypopigmentation and/or hyperpigmentation of the retinal pigment epithelium, and even choroidal neovascularization in certain patients. AMD is of two major forms: exudative (wet) and atrophic (dry) with changes affecting the macula leading to impaired vision. Although the retina remains an accessible portion for delivering drugs, there are no current options to cure or treat AMD. The existing expensive therapeutics are unable to treat the underlying pathology but display several side effects. However, recent innovations in nanotherapeutics provide an optimal alternative of drug delivery to treat the neovascular condition. These new-age technologies in the nanometer scale would enhance bioactivity and improve the bioavailability of drugs at the site of action to treat AMD. The nanomedicine also provides sustained release of the drug with prolonged retention after penetrating across the ocular tissues. In this review, the insights into the cellular and molecular mechanisms associated with the pathophysiology of AMD are provided. It also serves to review the current progress in nanoparticle-based drug delivery systems that offer feasible treatments in AMD.
Fulltext The Marine Natural Product Manzamine A Inhibits Cervical Cancer by Targeting the SIX1 Protein

Karan D, Dubey S, Pirisi L, Nagel A, Pina I, Choo YM, et al.

J Nat Prod, 2020 Feb 28;83(2):286-295.
PMID: 32022559 DOI: 10.1021/acs.jnatprod.9b00577

Natural products remain an important source of drug leads covering unique chemical space and providing significant therapeutic value for the control of cancer and infectious diseases resistant to current drugs. Here, we determined the antiproliferative activity of a natural product manzamine A (1) from an Indo-Pacific sponge following various in vitro cellular assays targeting cervical cancer (C33A, HeLa, SiHa, and CaSki). Our data demonstrated the antiproliferative effects of 1 at relatively low and non-cytotoxic concentrations (up to 4 μM). Mechanistic investigations confirmed that 1 blocked cell cycle progression in SiHa and CaSki cells at G1/S phase and regulated cell cycle-related genes, including restoration of p21 and p53 expression. In apoptotic assays, HeLa cells showed the highest sensitivity to 1 as compared to other cell types (C33A, SiHa, and CaSki). Interestingly, 1 decreased the levels of the oncoprotein SIX1, which is associated with oncogenesis in cervical cancer. To further investigate the structure-activity relationship among manzamine A (1) class with potential antiproliferative activity, molecular networking facilitated the efficient identification, dereplication, and assignment of structures from the manzamine class and revealed the significant potential in the design of optimized molecules for the treatment of cervical cancer. These data suggest that this sponge-derived natural product class warrants further attention regarding the design and development of novel manzamine analogues, which may be efficacious for preventive and therapeutic treatment of cancer. Additionally, this study reveals the significance of protecting fragile marine ecosystems from climate change-induced loss of species diversity.
Manzamine A reduces androgen receptor transcription and synthesis by blocking E2F8-DNA interactions and effectively inhibits prostate tumor growth in mice

Karan D, Dubey S, Gunewardena S, Iczkowski KA, Singh M, Liu P, et al.

Mol Oncol, 2024 Apr 11.
PMID: 38605607 DOI: 10.1002/1878-0261.13637

The androgen receptor (AR) is the main driver in the development of castration-resistant prostate cancer, where the emergence of AR splice variants leads to treatment-resistant disease. Through detailed molecular studies of the marine alkaloid manzamine A (MA), we identified transcription factor E2F8 as a previously unknown regulator of AR transcription that prevents AR synthesis in prostate cancer cells. MA significantly inhibited the growth of various prostate cancer cell lines and was highly effective in inhibiting xenograft tumor growth in mice without any pathophysiological perturbations in major organs. MA suppressed the full-length AR (AR-FL), its spliced variant AR-V7, and the AR-regulated prostate-specific antigen (PSA; also known as KLK3) and human kallikrein 2 (hK2; also known as KLK2) genes. RNA sequencing (RNA-seq) analysis and protein modeling studies revealed E2F8 interactions with DNA as a potential novel target of MA, suppressing AR transcription and its synthesis. This novel mechanism of blocking AR biogenesis via E2F8 may provide an opportunity to control therapy-resistant prostate cancer over the currently used AR antagonists designed to target different parts of the AR gene.