Bisphenol A-induced oxidative stress, hepatotoxicity and altered estrogen receptor expression in Labeo bata: impact on metabolic homeostasis and inflammatory response.

Bisphenol A (BPA), a weak estrogenic endocrine disruptor and a well-known plasticizer, has the potential to perturb diverse physiological functions; however, its impact on immune and metabolic function in aquatic vertebrates is relatively less understood. The present study aims to investigate the impact of BPA on hepatotoxicity, metabolic and immune parameters vis-à-vis estrogen receptor expression modulation in a freshwater teleost, Labeo bata (Cyprinidae, Cypriniformes). The 96-h median lethal concentration of BPA in L. bata has been determined as 4.79 mg/L. Our data demonstrate that congruent with induction of plasma vitellogenin (VTG), chronic exposure to sub-lethal BPA (2 and 4 µM/L) attenuates erythrocyte count, hemoglobin concentration, packed cell volume, mean corpuscular hemoglobin, but not leukocyte number. Further, a significant increase in MDA, concomitant with diminished catalase and heightened GST activity corroborates well with hepatic dystrophic changes, appearance of fatty liver (macrovesicular steatosis) and elevated serum lipids (triglyceride, cholesterol, LDL, VLDL) in BPA-treated groups. Interestingly, a differential regulation of estrogen receptor (ER) subtypes at transcript and protein level signifies negative influence of BPA on hepatic ERα/ERß homeostasis in this species. While at a lower dose it promotes Akt phosphorylation (activation), BPA at the higher dose attenuates ERK1/2 phosphorylation (activation), suggesting potential alteration in insulin sensitivity. Importantly, dose-dependent decrease in hepatic TNF-α, IL-1ß, iNOS (NOS2) expression and nitric oxide (NO) level corresponds well with progressive decline in p-NF-κB, p-p38 MAPK, albeit with differential sensitivity, in BPA-exposed groups. Collectively, BPA exposure has wide-spread negative influence on hematological, biochemical and hepatic events in this species.

Selective sensing of Al3+ ions by nitrophenyl induced coordination: imaging in zebrafish brain tissue.

A p-nitrophenyl based rhodamine probe (NPRB) has been designed and synthesized for the selective, real-time detection of Al(iii) in aqueous medium with a lower micromolar range detection limit at physiological pH. All the spectroscopic and theoretical analyses validated the proposed 1 : 1 complexation between NPRB and Al3+ along with an 80-fold enhancement in fluorescence intensity. Using the "turn on" response of the probe, binding of NPRB to Al3+ in the brain tissue of adult male zebrafish (D. rerio) has been visualized through fluorescence microscopy.

Nonylphenol attenuates SOCS3 expression and M1 polarization in lipopolysaccharide-treated rat splenic macrophages.

Endocrine disruptors interfere with normal sexual and reproductive development of numerous organisms. Widely used in several chemical and manufacturing industries, nonylphenol (NP), a potent xenoestrogen, has the potential to perturb immune system. Using rat splenic macrophages (SMΦ) as the model system, NP-modulation of lipopolysaccharide (LPS)-induced inflammatory response has been investigated. Our results demonstrate that NP (0.1-10 µM) attenuates catalase activity, reactive oxygen species (ROS) generation and nitric oxide (NO) synthesis in LPS-treated SMΦ in vitro. NP inhibition of LPS-induced nuclear factor kappa B (NF-κB) activation and pro-inflammatory cytokine gene expression corroborate well with attenuation of suppressor of cytokine signalling 3 (SOCS3). Besides, elevated expression of anti-inflammatory factors reveals inverse correlation with suppression of endotoxin-induced M1 polarization in NP pre-incubated cells. While LPS promotes, NP prevents ERK1/2 (extracellular-signa1-regulated kinase 1/2) phosphorylation and MEK-inhibitor abrogates SOCS3 expression and NO production suggesting involvement of ERK1/2 in NP inhibition of SOCS3 expression. Further, translational inhibitor cycloheximide prevents LPS-induced NF-κB activation indicating functional importance of de novo synthesis of SOCS3, at least in part, in toll-like receptor 4 (TLR4)-mediated inflammatory response. Collectively, present study provides evidence favouring participation of SOCS3 in NP modulation of inflammatory response in rat SMΦ.

Participation of follicular superoxides, inflammatory modulators, and endocrine factors in zebrafish (Danio rerio) ovulation: Cross-talk between PKA and MAPK signaling in Pgr regulation of ovulatory markers.

The ovulatory response involves diverse molecular determinants, the interplay between which remains less investigated in fish. This study explores the temporal changes in the follicular microenvironment, regulatory factors, and underlying signaling events during ovulation in female zebrafish subjected to 14L:10D at 28 ± 1 °C in vivo vis-à-vis in hCG-stimulated full-grown (FG) follicles in vitro. Congruent with reduced GSH levels, SOD, and GPx activity, a graded increase in follicular free radicals, Nox4, and p38 MAPK phosphorylation in the morning hour groups (05:00 and 06:30) correlates positively with the ovulatory surge in inflammatory mediators (Tnf-α, Il-1ß, Il-6, Nos2, and Cox-2). Further, elevated Pgr expression and its nuclear translocation, congruent with follicular lhcgr, star, and hsd20b2 upregulation in vivo, corroborates well with the transcriptional activation of genes (pla2g4aa, ptgesl, ptger4b, mmp9, adamts9), triggering ovulation in this species. Mechanistically, an elevated ovulatory response in hCG-treated FG follicles in vitro involves the upregulation of inflammatory mediators, pgr and ovulation-associated genes in a manner sensitive to PKA- and MAPK3/1-mediated signaling.

Leiomyoma of the palatine tonsil - report of a rare and unusual tumor at this site.

A leiomyoma is a remarkably rare cause of a benign, one-side tonsillar enlargement. The diagnosis is essentially histologic and will not normally be suspected clinically. Immunohistochemistry is needed for substantiation of the morphology and confirmation. We submit this illustrative case report.

Solitary fibrous tumor of the seminal vesicle.

Solitary fibrous tumors (SFTs) are mesenchymal neoplasms with variable clinical behavior depending on age, tumor site, and size, and pathologic factors such as mitoses and necrosis. Imaging features on computed tomography (CT) or magnetic resonance imaging (MRI) are not specific, and the diagnosis relies on histopathology with immunohistochemistry. SFTs arising from seminal vesicles is rare and reported in only eight earlier cases. We discuss the clinical, histopathologic and positron emission tomography (PET) imaging characteristics of a 54-year-old patient with SFT of the seminal vesicle. The patient was treated with robot-assisted seminal vesiculotomy and is doing well on follow-up at two years.

Primary dural follicular lymphoma masquerading as meningioma: a case report.

Patient presented with a dural-based mass lesion and was diagnosed as having meningioma on imaging. Post-resection histological examination revealed a low grade follicular lymphoma. The patient received cranial radiotherapy and is recurrence-free at 6-month follow-up. Primary dural follicular lymphoma is an exceedingly rare entity with only as few as six reported cases. Herein, the clinico-radio-pathological appearances and treatment protocol of this entity are discussed.

Reappraisal of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1/INI-1 deficient tumor: Report of two cases.

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 is a tumor suppressor gene located at chromosome 22q11.2. In the past decade, a major stride has been taken for decoding the molecular genesis of various tumors which has resulted in the addition of newer tumors harboring loss of this gene.

Chronic exposure to nonylphenol induces oxidative stress and liver damage in male zebrafish (Danio rerio): Mechanistic insight into cellular energy sensors, lipid accumulation and immune modulation.

Nonylphenol (NP), an environmentally persistent and toxic endocrine-disrupting chemical with estrogenic properties, has severe implications on humans and wildlife. Accumulating evidence demonstrates the toxic response of NP on the developmental process, nervous system, and reproductive parameters. Although NP exposure has been implicated in chronic liver injury, the underlying events associated with hepatic pathophysiology remain less investigated. Using male zebrafish (Danio rerio) as the model, the present study investigates the impact of environmentally relevant concentrations of NP (50 and 100 µg/L, 21 days) on hepatic redox homeostasis vis-à-vis cellular energy sensors, inflammatory response, and cell death involving a mechanistic insight into estrogen receptor (ER) modulation. Our results demonstrate that congruent with significant alteration in transcript abundance of antioxidant enzymes (SOD1, SOD2, Catalase, GPx1a, GSTα1), chronic exposure to NP promotes ROS synthesis, more specifically superoxide anions and H2O2 levels, and lipid peroxidation potentially through elevated NOX4 expression. Importantly, NP perturbation of markers associated with fatty acid biosynthesis (srebf1/fasn) and cellular energy-sensing network (sirt1/ampkα/pgc1α) indicates dysregulated energy homeostasis, metabolic disruption, and macrovesicular steatosis, albeit with differential sensitivity at the dose level tested. Besides, elevated p38-MAPK phosphorylation (activation) together with loss of ER homeostasis at both mRNA (esr1, esr2a, esr2b) and protein (ERα, ERß) levels suggest that NP modulation of ER abundance may have a significant influence on hepatic events. Elevated expression of inflammatory markers (TLR4, p-NF-κB, TNF-α, IL-6, IL-1ß, and NOS2) and pro-apoptotic and necrotic regulators, e.g., Bax, caspase- 8, -9 and cleaved PARP1 (50 kDa), indicate chronic inflammation and hepatotoxicity in NP-exposed males. Collectively, elevated oxidative stress, metabolic dysregulation and immune modulation may lead to chronic liver injury in organisms exposed to metabolic disrupting chemicals.

Extranodal Follicular dendritic cell sarcoma presenting as a rectal polyp: An entity overlooked by its differentials.

Extranodal follicular dendritic cell sarcoma (ENFDCS) is a rare hematolymphoid tumor, masquerading as soft tissue sarcoma on initial histological examination. So, for its confirmation, the application of immunohistochemistry (IHC) is of paramount importance. Over the years there has been a major shift in the demography of follicular dendritic cell sarcoma (FDCS), with a rise in the number of extranodal cases. Herein we report a case of ENFDCS presenting as a rectal polyp, who had a history of intermittent bleeding per rectum and passage of fleshy mass while defecation. As these tumors share an overlapping morphology with other spindle cell tumors and can occur at unpredictable locations, they pose a diagnostic challenge, especially for young pathologists.

Primary diffuse large B-cell lymphoma masquerading as uterine fibroid: A pathologistsf diagnosis.

Lymphoma involving the uterus is rare, and the diagnosis is usually difficult due to the rarity and nonspecific presentation. The treatment is often delayed and difficult because there is no standard treatment. We report our experience with a case of diffuse large B-cell lymphoma (DLBCL) involving the uterus. A 40-year-old female presented to our hospital posthysterectomy for suspected fibroid. Computed tomography scan and the tissue biopsy along with the immunoprofile revealed uterine DLBCL. She was treated with chemotherapy followed by radiation therapy and showed the complete response to the treatment, and thus, the clinicians should be aware of this rare disease for prompt diagnosis.

Bisphenol A impairs reproductive fitness in zebrafish ovary: Potential involvement of oxidative/nitrosative stress, inflammatory and apoptotic mediators.

Bisphenol A (BPA) is a highly pervasive chemical in consumer products with its ascribed endocrine-disrupting properties. Several studies have shown the cytotoxic, genotoxic, and carcinogenic property of BPA over a multitude of tissues. Although BPA exposure has earlier been implicated in female infertility, the underlying molecular mechanisms explaining the toxicity of BPA in the ovary remains less understood. In the present study, a plausible correlation between redox balance or inflammatory signaling and reproductive fitness upon BPA exposure has been examined in zebrafish (Danio rerio) ovary. Congruent with significant alteration of major antioxidant enzymes (SOD1, SOD2, catalase, GPx1α, GSTα1) at the transcript level, 30 d BPA exposure at environmentally relevant concentrations (1, 10 and 100 µg L-1) promotes ovarian ROS/RNS synthesis, lipid peroxidation but attenuates catalase activity indicating elevated stress response. BPA promotes a sharp increase in ovarian p38 MAPK, NF-κB phosphorylation (activation), inducible nitric oxide synthase (Nos2a), and pro-inflammatory cytokines (TNF-α and IL-1ß) expression, the reliable markers for inflammatory response. Congruent to an increased number of atretic follicles, BPA-exposed zebrafish ovary reveals elevated Bax/Bcl2 ratio, activation of caspase-8, -3 and DNA breakdown suggesting heightened cell death. Importantly, significant alteration in nuclear estrogen receptor (ER) transcripts (esr1, esr2a, and esr2b) and proteins (ERα, ERß), gonadotropin receptors, and markers associated with steroidogenesis and growth factor gene expression in BPA-exposed ovary correlates well with impaired ovarian functions and maturational response. Collectively, elevated oxidative/nitrosative stress-mediated inflammatory response and altered ER expression can influence ovarian health and reproductive fitness in organisms exposed to BPA environment.

Expression of nitric oxide synthase (NOS) in Anabas testudineus ovary and participation of nitric oxide-cyclic GMP cascade in maintenance of meiotic arrest.

Participation of cyclic nucleotide-mediated signaling in nitric oxide/soluble guanylate cyclase (NO/sGC) regulation of oocyte maturation (OM) in perch (Anabas testudineus) follicle-enclosed oocytes has been investigated. Congruent with sharp decline in follicular cyclic GMP (cGMP) level, nitric oxide synthase (NOS)-inhibitor (L-NAME) attenuates protein kinase A (PKA) phosphorylation but promotes p-ERK1/2 and p-p34Cdc2 (Thr-161) in maturing oocytes. Conversely, NO donor (SNP) prevents OM, potentially through elevated cGMP synthesis. Expression and localization of Nos2 and Nos3 immunoreactivity in perch ovary varied considerably at progressively higher stages of folliculogenesis. While sGC inhibitor (ODQ) alone could induce OM, 8-bromo-cGMP attenuates 17,20ß-P-induced OM indicating functional significance of NO/sGC/cGMP in perch ovary. Interestingly, high NO/cGMP inhibition of OM shows positive relation with elevated cAMP level. MIS induced OM is more susceptible to the oocyte-specific phosphodiesterase (PDE) 3 than PDE4 inhibition. Collectively, high NO/cGMP attenuation of OM potentially involves PDE3 inhibition, cAMP accumulation and PKA activation.

An unusual case of hepatic lymphoma with multiple epithelial malignancies.

Primary hepatic mucosa-associated lymphoid tissue lymphoma (MALToma) is a rare entity. Its coexistence with other malignancies is even rarer. Only few case reports of its association with other malignancies mostly gastric and colon cancer have been published. We report a case of primary MALToma of liver in an unusual setting of dual solid malignancy.

Significance of perineural invasion in locally advanced bucco alveolar complex carcinomas treated with surgery and postoperative radiation ± concurrent chemotherapy.

BACKGROUND: The purpose of this study was to evaluate prognostic factors, locoregional control, and survival in locally advanced bucco-alveolar complex cancers. METHODS: A retrospective review of 83 patients treated between January 2009 and December 2012 with bucco-alveolar complex cancers was conducted. All patients had surgery and adjuvant radiotherapy with intensity-modulated radiotherapy (IMRT) with/without concurrent chemotherapy. Survival analysis was performed using Kaplan-Meier and multivariable Cox regression model. RESULTS: On univariate and multivariate analysis, perineural invasion (PNI) was found to be an independent adverse risk factor. Patients with PNI-positive disease had significantly worse 2-year disease-free survival (DFS), locoregional failure free survival, and overall survival (OS) as compared to patients with PNI-negative disease (P < 0. 001, 0.001 and < 0. 001) respectively. CONCLUSION: Compared with patients with PNI-negative disease, patients with PNI-positive disease had much worse outcome despite aggressive adjuvant treatment. It warrants escalation of therapy and modification in radiation portals to cover neural pathways in patients with PNI-positive disease.

Primary retroperitoneal mucinous cystadenocarcinoma in a male patient.

Primary retroperitoneal mucinous neoplasms are extremely rare tumors. Less than sixty cases have been reported in international literature until date, with striking female predominance. We report a case of primary mucinous cystadenocarcinoma of the retroperitoneum in a 51-year-old male presenting with nonspecific abdominal complaints. This case is being highlighted for its rare occurrence in a male patient.