E3 ubiquitin ligase CBLB regulates innate immune responses and bacterial dissemination during nontuberculous mycobacteria infection.

Nontuberculous Mycobacteria (NTM) are emerging opportunistic pathogens causing pulmonary infection to fatal disseminated disease. NTM infections are steadily increasing in children and adults, and immune-compromised individuals are at a greater risk of fatal infections. The NTM disease's adverse pathology and the drug resistance to antibiotics have further worsened the therapeutic measures. Innate immune regulators are potential targets for therapeutics to NTM, especially in T cell suppressed population and many ubiquitin ligases modulate pathogenesis and innate immunity during infections, including mycobacterial infections. Here, we investigated the role of an E3 ubiquitin ligase, Casitas B-lineage lymphoma proto-oncogene B (CBLB), in immunocompromised mouse models of NTM infection. We found that CBLB is essential to prevent bacterial growth and dissemination. Cblb-deficiency debilitated NK cells, inflammatory monocytes, and macrophages in vivo. However, Cblb-deficiency in macrophages did not wane its ability to inhibit bacterial growth or production of reactive oxygen species nor the IFNγ production by NK cells in vitro. CBLB restricted the NTM growth and dissemination by promoting early granuloma formation in vivo. Our study shows that CBLB bolsters innate immune responses and helps prevent the dissemination of NTM during compromised T-cell immunity.

A smart coating with integrated physical antimicrobial and strain-mapping functionalities for orthopedic implants.

The prevalence of orthopedic implants is increasing with an aging population. These patients are vulnerable to risks from periprosthetic infections and instrument failures. Here, we present a dual-functional smart polymer foil coating compatible with commercial orthopedic implants to address both septic and aseptic failures. Its outer surface features optimum bioinspired mechano-bactericidal nanostructures, capable of killing a wide spectrum of attached pathogens through a physical process to reduce the risk of bacterial infection, without directly releasing any chemicals or harming mammalian cells. On its inner surface in contact with the implant, an array of strain gauges with multiplexing transistors, built on single-crystalline silicon nanomembranes, is incorporated to map the strain experienced by the implant with high sensitivity and spatial resolution, providing information about bone-implant biomechanics for early diagnosis to minimize the probability of catastrophic instrument failures. Their multimodal functionalities, performance, biocompatibility, and stability are authenticated in sheep posterolateral fusion model and rodent implant infection model.

Immunohistochemical evaluation of E-cadherin in oral epithelial dysplasia and squamous cell carcinoma.

Aim: To evaluate the expression of E-cadherin (E-cad) in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Material and Method: Immunohistochemistry was used to detect E-cad expression in 20 cases each of normal oral mucosa, oral epithelial dysplasia and squamous cell carcinoma. Statistical Analysis Used: Inferential statistical methods for statistical analysis used were Chi-square test for comparison of the frequency between different severity of dysplasia and OSCC. Results: Upon assessing the expression of E-cad in OED and OSCC, increase in E-cad immunoreactivity was seen in early lesions. However, the expression of E-cad decreased significantly as the grade of dysplasia increased. Conclusion: We observed a significant decrease in E-cad expression from dysplasia to poorly differentiated squamous cell carcinoma suggesting that loss of expression of E-cad is closely related to carcinoma.

GM-CSF+ Tc17 cells are required to bolster vaccine immunity against lethal fungal pneumonia without causing overt pathology.

GM-CSF co-expressing T17 cells instigate pathologic inflammation during autoimmune disorders, but their function in immunity to infections is unclear. Here, we demonstrate the role of GM-CSF+Tc17 cells for vaccine immunity against lethal fungal pneumonia and the cytokine requirements for their induction and memory homeostasis. Vaccine-induced GM-CSF+ Tc17 cells are necessary to bolster pulmonary fungal immunity without inflating pathology. Although GM-CSF expressing Tc17 cells preferentially elevate during the memory phase, their phenotypic attributes strongly suggest they are more like Tc17 cells than IFNγ-producing Tc1 cells. IL-1 and IL-23, but not GM-CSF, are necessary to elicit GM-CSF+ Tc17 cells following vaccination. IL-23 is dispensable for memory Tc17 and GM-CSF+ Tc17 cell maintenance, but recall responses of effector or memory Tc17 cells in the lung require it. Our study reveals the beneficial, nonpathological role of GM-CSF+ Tc17 cells during fungal vaccine immunity.

T cell responses to control fungal infection in an immunological memory lens.

In recent years, fungal vaccine research emanated significant findings in the field of antifungal T-cell immunity. The generation of effector T cells is essential to combat many mucosal and systemic fungal infections. The development of antifungal memory T cells is integral for controlling or preventing fungal infections, and understanding the factors, regulators, and modifiers that dictate the generation of such T cells is necessary. Despite the deficiency in the clear understanding of antifungal memory T-cell longevity and attributes, in this review, we will compile some of the existing literature on antifungal T-cell immunity in the context of memory T-cell development against fungal infections.

Effect of Killed PRRSV Vaccine on Gut Microbiota Diversity in Pigs.

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important pathogens affecting the global swine industry. Vaccination is still a main strategy for PRRSV control; however, host factors associated with vaccine efficacy remain poorly understood. Growing evidence suggests that mucosa-associated microbiomes may play a role in the responses to vaccination. In this study, we investigated the effects of a killed virus vaccine on the gut microbiome diversity in pigs. Fecal microbial communities were longitudinally assessed in three groups of pigs (vaccinated/challenged with PRRSV, unvaccinated/challenged with PRRSV, and unvaccinated/unchallenged) before and after vaccination and after viral challenge. We observed significant interaction effects between viral challenge and vaccination on both taxonomic richness and community diversity of the gut microbiota. While some specific taxonomic alterations appear to be enhanced in vaccinated/challenged pigs, others appeared to be more consistent with the levels in control animals (unvaccinated/unchallenged), indicating that vaccination incompletely protects against viral impacts on the microbiome. The abundances of several microbial taxa were further determined to be correlated with the level of viral load and the amount of PRRSV reactive CD4+ and CD8+ T-cells. This study highlights the potential roles of gut microbiota in the response of pigs to vaccination, which may pave the road for the development of novel strategies to enhance vaccine efficacy.

Desmoplastic ameloblastoma of anterior maxilla - A case report.

The recently recognized desmoplastic ameloblastoma is considered a rare variant of central ameloblastoma. It has been included in the World Health Organization's histopathological typing of odontogenic tumors, similar to benign, locally invasive tumors with low recurrence rate and peculiar histological features, characterized by epithelial changes due to the pressure of stroma on epithelial tissue. The aim of this paper is to report a unique case of desmoplastic ameloblastoma in the mandible of a 21-year-old male with a painless swelling in the anterior region of the maxilla. To our knowledge, only a few cases of adult patients affected by desmoplastic ameloblastoma have been published.

Comparison of calretinin expression in dentigerous cysts and ameloblastoma: An immunohistochemical study.

BACKGROUND: Calretinin is a calcium-binding protein of 29-kilodalton (kDa), which is widely expressed in normal human tissues and tumorigenic tissues. Its expression in the odontogenic epithelium during odontogenesis and in neoplastic odontogenic tissues has been demonstrated. Unicystic ameloblastoma poses a diagnostic challenge, as its histologic presentation can be sometimes mistaken for cystic odontogenic lesions. In the present study, an attempt is made to overcome the confusion encountered in the diagnosis of dentigerous cyst and unicystic ameloblastoma, using the expression of calretinin in both lesions and to compare this expression with conventional ameloblastoma to accurately diagnose and differentiate these lesions. MATERIALS AND METHODS: A total of eighty cases, in which twenty cases each of ameloblastoma, unicystic ameloblastoma, dentigerous cyst, and odontogenic keratocyst (OKC) were included in the study. Slides were made from the archival blocks of each case and were stained immunohistochemically with calretinin. RESULTS: Correlation between calretinin staining and histopathological diagnosis was done, and it was found that all twenty cases of ameloblastoma showed positivity for calretinin, whereas 17 of twenty cases of unicystic ameloblastoma showed positivity for calretinin staining. All the cases of OKC and dentigerous cyst were negative for calretinin. CONCLUSION: Calretinin may serve as an important diagnostic adjunct in the differential diagnosis of ameloblastoma and cystic odontogenic lesions.

Hormone receptor status of breast cancer in the himalayan region of northern India.

The role of hormone receptors as a prognostic and therapeutic tool in breast cancer is widely accepted. The frequency of nonreactivity of estrogen and progesterone receptors in breast cancer patients of India is much more common than in the West. This study was conducted with the aim of analysis of steroid receptor status in breast cancer with clinico-pathological characteristics from the northern hilly state of Himachal Pradesh, India located in the region of the Western Himalayas. Fifty five consecutive patients with the diagnosis of breast cancer were included in this study. Detailed clinical and histopathologic data was recorded in all cases. Estrogen receptor and progesterone receptor status was evaluated by immunohistochemistry. Chi-square test was used for statistical analysis. On immunohistochemical staining, 34.5% cases proved to be estrogen receptor positive and 36.4% cases progesterone receptor positive. The results in the present study documented low estrogen receptor and progesterone receptor positivity in breast cancer from this region of India.

Metastatic ovarian tumor.

58-year-old woman with a history of breast carcinoma presented with a bilateral ovarian tumor. On fine needle aspiration cytology, diagnosis of metastatic adenocarcinoma was made. At subsequent hysterectomy and bilateral salpingo-oophrectomy, specimen showed extensive metastatic carcinoma involving both ovaries.

Lymphoepithelioma-like carcinoma of the uterine cervix.

Lymphoepithelioma-like carcinoma (LELC) of the uterine cervix is a rare variant of squamous cell carcinoma (SSC). It differs from the usual SSC of the cervix in its morphology and clinical behavior and shows a better prognosis than the more common SSC of the cervix. We report a case of LELC of the cervix, diagnosed on the basis of histopathology in a 42-year-old female who presented with a history of postcoital bleeding.

Matrix-producing mammary carcinoma: a rare breast tumor.

Matrix-producing carcinoma of the breast is a unique subclass of metaplastic carcinoma which is characterized by the existence of a ductal carcinomatous component with direct transition to areas showing cartilagenous or osseous differentiation, lacking an interspersed spindle cell component. This article reports one such rare case in a 50-year-old woman who had a right breast mass. f0 ine needle aspiration (FNA) smears showed abundant chondromyxoid extracellular matrix to which were variably admixed carcinomatous cells. Histological examination revealed a neoplasm composed of invave ductal carcinoma with a direct transition to chondrosarcomatous areas. The case is reported not only for its peculiar microscopic characteristics but also to highlight its better prognostic features and hence, the need for its recognition.

Mucoepidermoid carcinoma arising in Warthin's tumor: a case report.

Malignant transformation of the epithelial component of Warthin's tumor is extremely rare. We describe our experience of mucoepidermoid carcinoma arising in Warthin's tumor of the parotid gland in a 35 year old female. The tumor removed from the parotid region was well encapsulated and histologically comprised ofmucoepidermoid carcinoma along with areas of Warthin's tumor. The pathogenesis and differential diagnosis of this rare occurrence have been discussed.