Fibroblastic reticular cell tumor of eyelid: Rare case report and review of literature.

Fibroblastic reticular cell tumours (FRCT) originate from the fibroblastic reticular cells (FBRC) which are histiocytic cells, belonging to the dendritic cell family. These tumours are extremely rare, with only a few cases reported in literature. Histomorphologically, they resemble follicular dendritic cell sarcoma (FDCS); however, they differ immunophenotypically. Extranodal presentations are rare. We report a case of malignant FBRC tumour of the left eyelid, in a 23-year-old woman, who had presented with a recurrent swelling over left lower eyelid. Microscopy revealed an ill circumbscribed tumour composed of oval to spindle cells in storiform pattern, sprinkled with lymphocytes. Immunohistochemistry was performed and diagnosis of FRCT was offered. To the best of our knowledge, this is the first report of malignant FBRC tumour arising in the eyelid region. Here we present this extremely rare case with review of the available literature.

Integrated single-cell transcriptomics reveals the hypoxia-induced inflammation-cancer transformation in NASH-derived hepatocellular carcinoma.

Non-alcoholic fatty liver disease (NAFLD) has emerged as the primary risk factor for hepatocellular carcinoma (HCC), owing to improved vaccination rates of Hepatitis B and the increasing prevalence of metabolic syndrome related to obesity. Although the importance of innate and adaptive immune cells has been emphasized, the malignant transformation of hepatocytes and their intricate cellular network with the immune system remain unclear. The study incorporated four single-cell transcriptomic datasets of liver tissues covering healthy and NAFLD-related disease status. To identify the subsets and functions of hepatocytes and macrophages, we employed differential composition analysis, functional enrichment analysis, pseudotime analysis, and scenic analysis. Furthermore, an experimental mouse model for the transformation of nonalcoholic steatohepatitis into hepatocellular carcinoma was established for validation purposes. We defined CYP7A1+ hepatocytes enriched in precancerous lesions as 'Transitional Cells' in the progression from NAFLD to HCC. CYP7A1+ hepatocytes upregulated genes associated with stress response, inflammation and cancer-associated pathways and downregulated the normal hepatocyte signature. We observed that hypoxia activation accompanied the entire process of inflammation-cancer transformation. Hepatocyte-derived HIF1A was gradually activated during the progression of NAFLD disease to adapt to the hypoxic microenvironment and hepatocytes under hypoxic environment led to changes in the metabolism, proliferation and angiogenesis, promoting the occurrence of tumours. Meanwhile, hypoxia induced the polarization of RACK1+ macrophages that enriched in the liver tissues of NASH towards immunosuppressed TREM2+ macrophages. Moreover, immunosuppressive TREM2+ macrophages were recruited by tumour cells through the CCL15-CCR1 axis to enhance immunosuppressive microenvironment and promote NAFLD-related HCC progression. The study provides a deep understanding of the development mechanism of NAFLD-related HCC and offers theoretical support and experimental basis for biological targets, drug research, and clinical application.

Assessment of Threshold Dose of Thoron Inhalation and Its Biological Effects by Mimicking the Radiation Doses in Monazite Placer Deposits Corresponding to the Normal, Medium and Very High Natural Background Radiation Areas.

The dose contributed from thoron (220Rn) and its progeny has been neglected in the dose assessment because of its short half-life (t1/2 = 55.6 s) and generally low concentrations. Recently, concentrations of 220Rn gas and its progeny were found to be pronounced in the traditional residential dwellings in China, on beaches of India and in other countries. Accordingly, we investigated the biological effects of thoron (220Rn) decay products in various mouse organs, succeeding inhalation of thoron gas in BALB/c mouse. We investigated the biological effects upon thoron inhalation on mouse organs with a focus on oxidative stress. These mice were divided into (4 random groups): sham inhalation, thoron inhalation for 1, 4 and 10 days. Various tissues (lung, liver and kidney) were then collected after the time points and subjected to various biochemical analyses. Immediately after inhalation, mouse tissues were excised for gamma spectrometry and 72 h post inhalation for biochemical assays. The gamma spectrometry counts and its subsequent calculation of the equivalent dose showed varied distribution in the lung, liver and kidney. Our results suggest that acute thoron inhalation showed a differential effect on the antioxidant function and exerted pathophysiological alterations via oxidative stress in organs at a higher dose. These findings suggested that thoron inhalation could alter the redox state in organs; however, its characteristics were dependent on the total redox system of the organs as well as the thoron concentration and inhalation time.

Thorium promotes lung, liver and kidney damage in BALB/c mouse via alterations in antioxidant systems.

Thorium (232Th), long lived (14.05 billion years) most stable thorium isotope, is thrice naturally abundant than uranium. 232Th occurs as rocky deposits and black monazite sands on the earth's crust geographically distributed in coastal South India and other places globally. Monazite sand comprises of cerium and large quantities of radioactive thorium. The environmental hazard lies in monazite rich area being termed as High Background Radiation Area (HBRA). In this study, we mimicked the HBRA under controlled chamber conditions using thorium oxalate as a thorium source for BALB/c mice exposure. Furthermore, sequential radio-disintegration of 232 Th leads to thoron (220Rn), the noble gas and other daughter products/progeny predominantly via alpha decay/emissions. Such progeny tend to attach to aerosol and dust particles having potential inhalation hazard followed by alpha emissions and damages that we evaluated in mouse lung tissues post thoron inhalation. Secondly, along with the radio disintegration and alpha emission, high energy gamma is also generated that can travel to various distant organs through the systemic circulation, as significant findings of our study as damages to the liver and kidney. The mechanistic findings include the damages to the hematological, immunological and cellular antioxidant systems along with activation of canonical NF-κß pathway via double stranded DNA damage.

Integrin αvß6 plays a bi-directional regulation role between colon cancer cells and cancer-associated fibroblasts.

Tumor microenvironment (TME) is the cellular environment in which tumor exists, and it contributes to tumor formation and progression. The TME is composed of tumor cells, stromal cells, cytokines, and chemotactic factors of which fibroblasts are the main cellular components. In our present study, we found that colorectal cancer (CRC) cells expressing integrin αvß6 clearly could induce morphological changes in inactive fibroblasts and increased the expression of activated fibroblast markers such as α-smooth muscle actin (α-SMA) and fibroblast-activating protein (FAP). Those activated fibroblasts in the TME are called cancer-associated fibroblasts (CAFs). In order to investigate the mechanism by which CRC cells expressing integrin αvß6 activated CAFs, a series of assays have been carried out in the follow-up. We found that CRC cells could secrete inactive transforming growth factor ß (TGF-ß); however, integrin αvß6 activated TGF-ß, which subsequently activated fibroblasts. This process was disrupted by knockdown of integrin αvß6. In contrast, activated fibroblasts could promote CRC cell invasion. In particular, the strengthening effect on expression of integrin αvß6 in colon cancer cells was obvious. Additionally, we found that CAFs could secrete stromal cell-derived factor-1 (SDF-1) and promote CRC cell metastasis in distant organs via the SDF-1/C-X-C chemokine receptor type 4 (CXCR4) axis. Taken together, we assumed that CRC cells and CAFs activated one another and worked together to promote cancer progression, with integrin αvß6 playing a role in the bi-directional regulation of these cells. Hence, integrin αvß6 may serve as a therapeutic target for the future CRC treatment.

Acetylpuerarin inhibits oxygen-glucose deprivation-induced neuroinflammation of rat primary astrocytes via the suppression of HIF-1 signaling.

In the central nervous system (CNS), ischemic injury induced by inflammation associated with astrocytes serves an important role in physiological and pathological processes. Neuroinflammation leads to the release of pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-1ß. The aim of the present study was to investigate whether acetylpuerarin attenuates oxygen-glucose deprivation (OGD)-induced astrocyte inflammation and secretion of pro-inflammatory cytokines via inhibiting hypoxia-inducible factor-1 (HIF-1) activation and suppressing downstream primary astrocyte signaling in rats. The results demonstrated that acetylpuerarin attenuates astrocyte viability and induces morphological changes following OGD stress. Furthermore, acetylpuerarin suppresses the stimulation of HIF-1α and nuclear factor (NF)-κB signaling pathways, while attenuating the expression and secretion of pro-inflammatory cytokines via HIF-1 suppression in OGD-induced astrocytes. These findings indicate that acetylpuerarin may attenuate OGD-induced astrocyte damage and inflammation in rat primary astrocytes via suppressing HIF-1 activation and NF-κB signaling. These results suggest that acetylpuerarin regulates inflammation associated with astrocytes and may represent a novel therapeutic agent for the treatment of neuroinflammation in the CNS.

Autographa californica Multiple Nucleopolyhedrovirus AC83 is a Per Os Infectivity Factor (PIF) Protein Required for Occlusion-Derived Virus (ODV) and Budded Virus Nucleocapsid Assembly as well as Assembly of the PIF Complex in ODV Envelopes.

Baculovirus occlusion-derived virus (ODV) initiates infection of lepidopteran larval hosts by binding to the midgut epithelia, which is mediated by per os infectivity factors (PIFs). Autographa californica multiple nucleopolyhedrovirus (AcMNPV) encodes seven PIF proteins, of which PIF1 to PIF4 form a core complex in ODV envelopes to which PIF0 and PIF6 loosely associate. Deletion of any pif gene results in ODV being unable to bind or enter midgut cells. AC83 also associates with the PIF complex, and this study further analyzed its role in oral infectivity to determine if it is a PIF protein. It had been proposed that AC83 possesses a chitin binding domain that enables transit through the peritrophic matrix; however, no chitin binding activity has ever been demonstrated. AC83 has been reported to be found only in the ODV envelopes, but in contrast, the Orgyia pseudotsugata MNPV AC83 homolog is associated with both ODV nucleocapsids and envelopes. In addition, unlike known pif genes, deletion of ac83 eliminates nucleocapsid formation. We propose a new model for AC83 function and show AC83 is associated with both ODV nucleocapsids and envelopes. We also further define the domain required for nucleocapsid assembly. The cysteine-rich region of AC83 is also shown not to be a chitin binding domain but a zinc finger domain required for the recruitment or assembly of the PIF complex to ODV envelopes. As such, AC83 has all the properties of a PIF protein and should be considered PIF8. In addition, pif7 (ac110) is reported as the 38th baculovirus core gene.IMPORTANCE ODV is essential for the per os infectivity of the baculovirus AcMNPV. To initiate infection, ODV binds to microvilli of lepidopteran midgut cells, a process which requires a group of seven virion envelope proteins called PIFs. In this study, we reexamined the function of AC83, a protein that copurifies with the ODV PIFs, to determine its role in the oral infection process. A zinc finger domain was identified and a new model for AC83 function was proposed. In contrast to previous studies, AC83 was found to be physically located in both the envelope and nucleocapsid of ODV. By deletion analysis, the AC83 domain required for nucleocapsid assembly was more finely delineated. We show that AC83 is required for PIF complex formation and conclude that it is a true per os infectivity factor and should be called PIF8.

Evaluation of facial artery perforator-based flaps in reconstruction of facial defects.

INTRODUCTION: Several flaps have been described for reconstructing facial or oral defects. Flaps such as forehead and pectoralis major are often too bulky for small-to-moderate-sized defects, for which nasolabial flaps are often ideal. However, nasolabial flaps have limited mobility and reach and may need two stages, particularly for intraoral defects. According to recent literatures, facial artery provides numerous small cutaneous perforators, based on which skin flaps can be islanded, with greater mobility and reach for reconstruction of small-to-moderate-sized intraoral and facial defects in one stage. Our study aims to evaluate the reliability and versatility of facial artery perforator-based flaps in the reconstruction of such defects. MATERIALS AND METHODS: A ethical committee-approved retrospective study was conducted on data of the patients attending our outpatient department between February 2014 and October 2015 with small-to-moderate-sized facial/oral lesions. The total sample size was 23. We studied the relation of flap survival with size of flap, route of inset and neck dissection, functional and aesthetic outcomes and feasibility of adjuvant therapy in cases of malignancies. RESULTS AND ANALYSIS: A wide range of facial defects, especially intraoral defects, could be reconstructed in one stage using facial artery perforator-based flaps. The flaps were reliable. Complications included only partial skin loss of the flaps in a few cases. Complications were directly related to the length of the flaps and the route of inset. Functional and aesthetic outcomes were satisfactory and none of the flaps showed any significant post-radiotherapy changes. CONCLUSIONS: We concluded that facial artery perforator flap can be a simple, safe, versatile and one-stage alternative to the traditional flaps in the reconstruction of small-to-moderate-sized facial defects. Neck dissection can be safely done in the same sitting.

Integrin ß6 serves as an immunohistochemical marker for lymph node metastasis and promotes cell invasiveness in cholangiocarcinoma.

Cholangiocarcinoma is a devastating malignancy that is notoriously difficult to diagnose and is associated with a high mortality. Despite extensive efforts to improve the diagnosis and treatment of this neoplasm, limited progress has been made. Integrin ß6 is a subtype of integrin that is expressed exclusively on the surfaces of epithelial cells and is associated with a variety of tumors. In the present study, we investigated the expression and roles of integrin ß6 in cholangiocarcinoma. ß6 upregulation in cholangiocarcinoma was correlated with lymph node metastasis and distant metastasis. Moreover, integrin ß6 was identified as a biomarker for the diagnosis of cholangiocarcinoma and an indicator of lymph node metastasis. Integrin ß6 significantly promoted the proliferation, migration and invasion of cholangiocarcinoma cells. Furthermore, integrin ß6 increased Rac1-GTPase, resulting in the upregulation of metalloproteinase-9 (MMP9) and F-actin polymerization. Taken together, our results indicate that integrin ß6 promotes tumor invasiveness in a Rac1-dependent manner and is a potential biomarker for tumor metastasis. Integrin ß6 may help to improve the diagnostic accuracy, and targeting ß6 may be a novel strategy for the treatment of cholangiocarcinoma.

Intrahepatic biliary papillomatosis associated with malignant transformation: report of two cases and review of the literature.

Biliary papillomatosis (BP) is a rare disease characterized by multiple numerous papillary adenomas in both the intrahepatic and extrahepatic biliary tree. Due to its high recurrence rate and frequent transformation to malignancy, BP should not be considered a benign disease, and a radical resection with an adequate resection margin is advocated in cases of localized intrahepatic biliary papillomatosis. Since BP is a rare disease and its clinical features and outcomes are not well known, it's really difficult to diagnose the disease before operation. We encountered two cases diagnosed as intrahepatic biliary papillomatosis postoperatively, and herein present the diagnostic difficulties and therapeutic options for this rare disease.

Congenital urethrocutaneous fistula-our experience with nine cases.

Congenital urethrocutaneous fistula is a very rare anomaly with about 40 odd cases reported in literature till 2008 .We present here 9 such cases all of whom were uncircumcised at presentation.7 out of 9 cases had a fistula in the distal shaft and the rest 2 cases had a fistula in the mid-shaft of the penis with an associated chordee.Associated congenital anomaly was present in only one case which had an associated imperforate anus . When the fistula was present distally , we did a primary repair of the fistula which was reinforced by a Bayer's Flap. When the fistula was present in the mid shaft we did a Primary repair of the fistula & reinforced it by a Tunica Vaginalis Flap.

Foreign bodies in urinary bladders.

We studied the patients admitted in our hospital with intravesical foreign bodies from February 2007 to January 2009 regarding their clinical presentation, nature of the foreign bodies, and methods used to remove them. The patients with intravesical foreign bodies were investigated and underwent cystoscopy for direct visualization of the foreign body and an attempt to remove it through the cystoscope. If cystoscopic removal failed, then suprapubic cystostomy was done to remove it. Nine patients (six males and three females, with a mean age of 24.5 years) with intra-vesical foreign bodies were admitted during the study period. In all the female patients and one male patient, foreign bodies were introduced inside the bladder by the patients themselves. In four cases, the foreign bodies were iatrogenic in nature, and in one case, it migrated accidentally through the urethra. In conclusion, intravesical foreign bodies are not very uncommon. Self-introduced and iatrogenic foreign bodies into the bladder are more common than accidental migration through the urethra. Cystoscopic removal is successful in most of the cases. If cystoscopic removal is not possible, then suprapubic cystostomy is required to accomplish this task.

Heteropagus twins-a tale of two cases.

Heteropagus twinning is a rare occurrence. Parasitic and asymmetric conjoined twins are rarer anomalies of monochorionic monoamniotic twins; which consist of an incomplete twin attached to the fully developed body of the co-twin. We present here two such cases of Heteropagus twinning.

A comparative study of two techniques of urethroplasty in repair of distal penile hypospadias.

Hypospadias is a common congenital anomaly of the penis in which the urethra opens proximal to its normal position at the tip of the glans and the overall incidence of hypospadias is between 0.3% and 0.6%. Distal penile hypospadias is the commonest amongst all hypospadias cases. One stage urethroplasty was performed among 64 cases using Mathieu-Mullen's procedure or Snodgrass Belman procedure. Of these 64 cases, in 29 cases the Mathieu-Mullen's procedure was followed and in the rest 35 cases of distal penile hypospadias the Snodgrass Belman procedure was employed. These two procedures were retrospectively compared in terms of operating time, operative blood loss, cosmetic result, postoperative fistula rate, duration of operation.

Transverse testicular ectopia with persistent Muellerian duct syndrome.

A one-year-old boy was admitted with complaints of swelling in the left inguinoscrotal region and an empty right scrotum since birth. The inguinoscrotum contained two ovoid solid swellings one above the other. The swellings were testes like in feel, size and shape. The diagnosis was transverse testicular ectopia. The case was managed by surgery. Tissue from gonads, the tubular structures and the fallopian tubes were sent for histopathological examination for confirmation. This was a case of an otherwise normal male with transverse testicular ectopia with persistent Muellerian duct syndrome in the left inguinoscrotal hernial sac.

Cytogenetic study of non-Hodgkin lymphoma from South India. histologic and geographic correlations.

Cytogenetic analysis of fine needle aspiration cultures was performed on 189 patients with non-Hodgkin lymphoma from South India. Successful karyotyping was possible in 97 patients (51.3%). Burkitt lymphoma constituted 56% of the cases studied followed by diffuse type 20%, follicular 8.8%, lymphoblastic 6.6%, and unclassified 6.6%. Characteristic chromosomal translocations were t(8;14)(q24;q32) [32.2%], t(8;22)(q24;q11) [10%], t(2;8)(p12;q24) [2.2%], t(14;18)(q34;q21) [3.3%], and t(11;14)(q23;q32) [2.2%]. Notable geographical variation of some structural abnormalities was the finding in the present study such as, lower frequency of t(14;18) in follicular lymphomas and higher frequency of t(8;14) in Burkitt lymphomas when compared with the Western studies.