Gymnemic acid protects murine pancreatic ß-cells by moderating hyperglycemic stress-induced inflammation and apoptosis in type 1 diabetic rats.

Type 1 diabetes is a chronic immune-mediated disease caused by pancreatic ß-cell dysfunction with consequent severe insulin deficiency. Exacerbated blood glucose levels can cause oxidative stress in the pancreatic ß-cells, which leads to inflammation, and apoptosis resulting in islet dysfunction. Although massive studies have been carried out to elucidate the causative factors for ß-cell damage in diabetes, the therapeutic approach to pancreatic ß-cell damage has not been extensively studied. Hence, the present study has been designed to delineate the role of gymnemic acid (GA) in protecting pancreatic ß-cells in diabetic animals, with special reference to inflammation and apoptosis. Our data revealed that the treatment with GA significantly reverted the alteration in both biochemical and histochemical observations in young diabetic rats. Moreover, treatment with the GA downregulates the expression of proinflammatory markers (nuclear factor-κB, tumor necrosis factor-α, interleukin-[IL]-6, and IL-1ß), proapoptotic proteins (Bax, cytochrome c, and cleaved caspase-3), as well as upregulates the expression of antiapoptotic protein Bcl-2 in diabetic rats. These findings suggest that the anti-inflammatory and antiapoptotic nature of GA mitigates ß-cell damage in hyperglycemic rats.

Farnesol alleviates diethyl nitrosamine induced inflammation and protects experimental rat hepatocellular carcinoma.

Hepatocellular carcinoma is a well-known internal malignancy with increased worldwide mortality. The increased progression rate is closely associated with chronic liver diseases such as cirrhosis. Chemical carcinogens cause tumor advocacy over free radical metabolites to causes numerous biochemical and molecular changes that bring oxidative stress. In addition, inflammatory cells and its growth factor promotes the progression of liver cancer through deregulates the numerous cellular signaling pathways involved in normal cellular proliferation. Plant derived phytochemicals have a better complimentary potency to defend against a wide array of free radical mediated diseases such as cancer. More recently, we have evaluated the anticancer effect of Farnesol against DEN induced hepatocellular carcinoma in male wistar albino rats. However, the possible mechanism in which Farnesol attributes its anticancer effect against DEN induced liver cancer remains unknown. Hence in the present study, an attempt has been made to reduce the oxidative stress by appraise the antioxidant effect by Farnesol in DEN induced hepatocellular carcinoma. Elevated oxidative stress markers with concomitant decreased cellular antioxidants levels were observed in DEN induced hepatic tissues. Further, proliferating nuclei with increased proliferating cell nucleolar antigen (PCNA) and inflammatory mediator expression were observed in DEN induced rats. Oral supplementation of Farnesol to DEN induced rats significantly decrease the oxidative stress markers and increase the cellular antioxidant status. Moreover, Farnesol treatment decreases the argyrophilic nuclear organizer region and PCNA along with decreased expression of inflammatory mediators suggest that Farnesol treatment restores DEN induced hepatic abnormalities and protects liver from cancer progression.

Citral inhibits N-nitrosodiethylamine-induced hepatocellular carcinoma via modulation of antioxidants and xenobiotic-metabolizing enzymes.

Hepatocellular carcinoma (HCC) ranks the sixth position among various cancers worldwide. Recent research shows that natural and dietary compounds possess many therapeutic effects. Citral is a monoterpene aldehyde that contains geranial and neral. The present study was considered to study the role of citral against N-nitrosodiethylamine (NDEA)-induced HCC via modulation of antioxidants and xenobiotic-metabolizing enzymes in vivo. NDEA-alone-administered group II animals profoundly showed increased tumor incidence, reactive oxygen species, liver marker enzyme levels, serum bilirubin levels, tumor markers of carcinoembryonic antigen, α-fetoprotein, proliferative markers of argyrophilic nucleolar organizing regions, proliferating cell nuclear antigen (PCNA) expressions, phase I xenobiotic-metabolic enzymes and simultaneously decreased antioxidants, and phase II enzymes levels. Citral (100 mg/kg b.w.) treatment significantly reverted the levels in group III cancer-bearing animals when compared to group II cancer-bearing animals. In group IV animals, citral-alone administration did not produce any adverse effect during the experimental condition. Based on the results, citral significantly inhibits the hepatocellular carcinogenesis through restoring the antioxidants and phase II xenobiotic-enzyme levels; thereby, it strongly proves as an antiproliferative agent against rat HCC.

Hepatoprotective effect of boldine against diethylnitrosamine-induced hepatocarcinogenesis in wistar rats.

Discovering the utmost effective and targeted chemotherapy for hepatocellular carcinoma is still a significant challenge. In the present study, diethylnitrosamine was used as a liver carcinogen and boldine a compound of boldo. We anticipated the hypothesis that boldine endow antiproliferative and promote apoptosis on hepatocarcinoma rats. We analyzed that boldine alters the tumor biomarkers and liver markers enzyme levels. Also, we determined boldine modulate the enzymatic and nonenzymatic antioxidant activities, as well as messenger RNA and protein expressions of Bcl2, Bax, and cleaved caspase 3 by reverse transcription polymerase chain reaction and Western blot analysis, respectively. It was also manifested by histopathology studies in liver tissues of HCC rats. Our finding suggested that boldine has antioxidant activity, and moreover, also contributes apoptotic nature by upregulating the protein expression of Bax, and cleaved caspase 3. Our data accomplishes that boldine a candidate drug has dynamic therapeutic activity and suitable for the treatment of HCC.

Microcystic adnexal carcinoma of the orbit mimicking pagetoid sebaceous gland carcinoma.

Microcystic adnexal carcinoma (MAC) is a rare malignancy of sweat glands that has been reported most often on the face in the form of a cutaneous lesion, with the potential for deeper invasion. The synonyms of MAC include sclerosing sweat duct carcinoma, syringomatous carcinoma, and malignant syringoma. Clinically, MAC in the periocular area has been misdiagnosed as basal cell carcinoma, squamous cell carcinoma, or even chalazia. We report a case of MAC presenting clinically as sebaceous gland carcinoma with pagetoid spread for the first time in literature.

Localized orbital amyloidosis - A varied presentation.

Localized orbital amyloidosis is rare, usually slowly progressive and benign disorder. The most common signs and symptoms include visible periocular mass, ptosis, proptosis, globe displacement, ocular motility disturbances, recurrent periocular subcutaneous hemorrhages, and dry eyes. Herein, we report a case of localized recurrent orbital amyloidosis with strabismus, restricted eye movement, ptosis, and orbital mass as the presentation in a 60-year-old female and managed with debulking and strabismus surgery, resulting in a good cosmetic and functional outcome.

Potential Chemopreventive Role of Boldine Against Hepatocellular Carcinoma via Modulation of Cell Cycle Proteins in Rat Model.

BACKGROUND: To evaluate the chemopreventive potential of boldine against diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) in Wistar albino rats. OBJECTIVE: Boldine is an alkaloid isolated from Peumus boldus. The primary active constituents of boldine exhibited several potential medicinal properties. The present study was evaluated to explore the chemopreventive agent of boldine on anti-proliferative efficacy against diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) in Wistar albino rats. METHODS: The effect of boldine on cellular proliferative markers, i.e., PCNA and Ki67on hepatocellular carcinoma rats was determined by immuno expression study. Liver marker enzymes, tumor biomarker, oxidative stress markers, antioxidant status, and xenobiotic phase I and II enzymes in HCC rats were analyzed. Moreover, cell cycle proteins, i.e., p21Cip1/Kip1and p27 Cip1/Kip1, Cyclin D1, CDK 4, Cyclin E1, and CDK 2 were investigated using immuno expression analysis. RESULTS: Treatment of boldine protected the liver against reactive oxygen species such as hydrogen peroxide, superoxide, protein carbonyl, and lipid peroxide during hepatocarcinogenesis by boosted antioxidants-superoxide dismutase (SOD), catalase (CAT). Boldine caused a substantial enhanced detoxification process by moderating phase I and II xenobiotic-metabolizing enzymes. Besides, the study found that boldine significantly inhibited the cellular proliferative markers like PCNA and Ki67 and regulated the specific cell cycle-associated proteins by up-regulated expression of p21Cip1/Kip1and p27 Cip1/Kip1 and down-regulated expression of Cyclin D1, CDK 4, Cyclin E1, and CDK 2. CONCLUSION: Our data manifests the anti-proliferative effect of boldine, which negatively modulates cellular proliferation and regulates cell cycle by protecting the cell from reactive oxygen species (ROS), suggesting that boldine establishes it as a chemopreventive agent in diethylnitrosamine-induced hepatocarcinogenesis in rats.

Mucoepidermoid carcinoma of the conjunctiva with lung metastasis.

A 36-year-old lady presented with redness and decreased vision in right eye since 6 months. She was earlier diagnosed of cavitary lung lesion, presumed secondary to tuberculosis and treated with anti-tubercular treatment for 4 months. Examination of affected right eye revealed nil light perception, conjunctival congestion with an exuberant mass in the inferotemporal bulbar conjunctiva, proptosis, iris neovascularization, 360° closed angles, intraocular pressure of 48 mm Hg, exudative retinal detachment, uveal mass and orbital extension. A diagnostic needle biopsy of uveal mass revealed malignant cells. Computed tomography-guided lung biopsy revealed squamous cell carcinoma (SCC), indicating metastatic spread from the orbit. She underwent lid-sparing exenteration of the right eye. Histopathological examination of the orbital tissue revealed mucoepidermoid carcinoma arising from the conjunctiva with extensive invasion into the orbital tissue, muscle fibers, sclera, choroid and optic nerve. Multiple tumor emboli were seen in the lumen of orbital blood vessels. In conclusion, mucoepidermoid carcinoma of the conjunctiva is a rare, aggressive variant of SCC. Early intervention is essential to prevent intraocular invasion and systemic metastasis.

Primary liposarcoma of the orbit: a clinicopathological study.

Primary liposarcoma of the orbit is a rare tumour. There are very few cases of orbital liposarcoma reported in the literature, mostly of the myxoid variety. In this paper, the authors report the clinical presentation, histopathological features, results of diagnostic studies and management of a case of orbital low grade myxoliposarcoma with local recurrence, together with a review of the literature.

Prepucial skin graft for forniceal and socket reconstruction in complete cryptophthalmos with congenital cystic eye.

We report the case of a 23-day-old boy with unilateral complete cryptophthalmos and congenital cystic eye, who had no associated systemic anomalies. We describe the technique of socket reconstruction with autologous prepucial skin graft used in this patient.