Extensive protein pyrophosphorylation revealed in human cell lines.

Reversible protein phosphorylation is a central signaling mechanism in eukaryotes. Although mass-spectrometry-based phosphoproteomics has become routine, identification of non-canonical phosphorylation has remained a challenge. Here we report a tailored workflow to detect and reliably assign protein pyrophosphorylation in two human cell lines, providing, to our knowledge, the first direct evidence of endogenous protein pyrophosphorylation. We manually validated 148 pyrophosphosites across 71 human proteins, the most heavily pyrophosphorylated of which were the nucleolar proteins NOLC1 and TCOF1. Detection was consistent with previous biochemical evidence relating the installation of the modification to inositol pyrophosphates (PP-InsPs). When the biosynthesis of PP-InsPs was perturbed, proteins expressed in this background exhibited no signs of pyrophosphorylation. Disruption of PP-InsP biosynthesis also significantly reduced rDNA transcription, potentially by lowering pyrophosphorylation on regulatory proteins NOLC1, TCOF1 and UBF1. Overall, protein pyrophosphorylation emerges as an archetype of non-canonical phosphorylation and should be considered in future phosphoproteomic analyses.

SERPINA11 related novel serpinopathy - A perinatal lethal disorder.

SERPINA11 is a hitherto poorly characterised gene belonging to Clade A of the SERPIN superfamily, with unknown expression pattern and functional significance. We report a perinatal lethal phenotype in two foetuses from the same family associated with a biallelic loss of function variant in SERPINA11, and provide functional evidence to support its candidature as a Mendelian disorder. The SERPINA11 variant-associated foetal phenotype is characterised by gross and histopathological features of extracellular matrix disruption. Western blot and immunofluorescence analyses revealed SERPINA11 expression in multiple mouse tissues, with pronounced expression in the bronchiolar epithelium. We observed a significant decrease in SERPINA11 immunofluorescence in the affected foetal lung compared with a healthy gestation-matched foetus. Protein expression data from HEK293T cell lines following site-directed mutagenesis support the loss of function nature of the variant. Transcriptome analysis from the affected foetal liver indicated the possibility of reduced SERPINA11 transcript abundance. This novel serpinopathy appears to be a consequence of the loss of inhibition of serine proteases involved in extracellular matrix remodelling, revealing SERPINA11 as a protease inhibitor critical for embryonic development.

Nanoencapsulation of Docetaxel Induces Concurrent Apoptosis and Necroptosis in Human Oral Cancer Cells (SCC-9) via TNF-α/RIP1/RIP3 Pathway.

Human oral squamous cell carcinoma is the sixth most frequent malignant cancer, with an unacceptably high death rate that affects people's health. Albeit, there are several clinical approaches for diagnosing and treating oral cancer they are still far from ideal. We previously synthesised and characterised the docetaxel nanoformulation (PLGA-Dtx) and discovered that docetaxel nanoencapsulation may suppress oral cancer cells. The goal of this study was to figure out the mechanism involved in the suppression of oral cancer cell proliferation. We discovered that PLGA-Dtx inhibited SCC-9 cell growth considerably as compared to free docetaxel (Dtx), and that the viability of SCC-9 cells treated with PLGA-Dtx was decreased dose-dependently. MTT assay showed that PLGA-Dtx selectively inhibited the growth of PBMCs from oral cancer patients while sparing PBMCs from normal healthy controls. Further, flow cytometry analysis showed that PLGA-Dtx induced apoptosis and necroptosis in SCC-9 cells. G2/M cell cycle arrest has been confirmed on exposure of PLGA-Dtx for 24 h in SCC-9 cells. Interestingly, western blot investigation found that PLGA-Dtx increased the amounts of necroptic proteins and apoptosis-related proteins more efficiently than Dtx. Furthermore, PLGA-Dtx was more effective in terms of ROS generation, and mitochondrial membrane potential depletion. Pretreatment with necroptosis inhibitor Nec-1 efficiently reversed the ROS production and further recover MMP caused by PLGA-Dtx. Overall, this study revealed a mechanistic model of therapeutic response for PLGA-Dtx in SCC-9 cells and proposed its potency by inducing cell death via activation of concurrent apoptosis and necroptosis in SCC-9 cells via TNF-α/RIP1/RIP3 and caspase-dependent pathway.

Increased Serum Levels of Matrix-metalloproteinase-9, Cyclo-oxygenase-2 and Prostaglandin E-2 in Patients with Chronic Obstructive Pulmonary Disease (COPD).

Chronic obstructive pulmonary disease (COPD), a heterogeneous lung disorder that is characterized by airflow obstruction and the third leading cause of death, globally. COPD is influenced by environmental and genetic factors. Here, we measured the serum level of matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2) and prostaglandin E-2 (PGE-2) and reveal the correlation between their levels in COPD subjects. In this study, we included a total of 79 COPD and 79 healthy controls. We assessed demographic profile, risk factors, respiratory symptoms, clinical history, COPD Assessment Test (CAT) score and spirometry. Further, we determined the serum levels of MMP-9, COX-2 and PGE-2 by enzyme-linked immunosorbent assay (ELISA). The correlation between their serum levels was also determined. Among the studied population age, gender, body mass index and socioeconomic status were comparable. Serum levels of MMP-9, COX-2 and PGE-2 were significantly increased in the COPD group than in healthy controls (P < 0.0001). Moreover, MMP-9, COX-2 and PGE-2 levels were increased with the GOLD grades and CAT score (> 10). Serum levels of MMP-9, COX-2 and PGE-2 was enhanced in patients with larger clinical history (> 20 years) than those with lower clinical history (< 10 years). Serum levels of MMP-9 and COX-2; MMP-9 and PGE-2; COX-2 and PGE-2 showed a positive correlation (P < 0.0001) with the COPD group. Our data demonstrate that serum levels of MMP-9, COX-2 and PGE-2 were correlated with the GOLD grade, CAT score and clinical history of the COPD group, pointing that they can be used as a indicators to understand the disease progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-021-00973-2.

Mechanistic insights and therapeutic opportunities of antimicrobial chemokines.

Chemokines are a family of small proteins best known for their ability to orchestrate immune cell trafficking and recruitment to sites of infection. Their role in promoting host defense is multiplied by a number of additional receptor-dependent biological activities, and most, but not all, chemokines have been found to mediate direct antimicrobial effects against a broad range of microorganisms. The molecular mechanism(s) by which antimicrobial chemokines kill bacteria remains unknown; however, recent observations have expanded our fundamental understanding of chemokine-mediated bactericidal activity to reveal increasingly diverse and complex actions. In the current review, we present and consider mechanistic insights of chemokine-mediated antimicrobial activity against bacteria. We also discuss how contemporary advances are reshaping traditional paradigms and opening up new and innovative avenues of research with translational implications. Towards this end, we highlight a developing framework for leveraging chemokine-mediated bactericidal and immunomodulatory effects to advance pioneering therapeutic approaches for treating bacterial infections, including those caused by multidrug-resistant pathogens.

Smokeless tobacco control: Litigation & judicial measures from Southeast Asia.

Recourse to litigation and positive judicial interventions is one of the most effective tools to meet public health objectives. The present review envisions compiling litigation and judicial measures in Southeast Asia Region (SEAR) while assessing their role in advancing smokeless tobacco (SLT) control, and equally highlighting, how tobacco industry has used litigation to undermine tobacco control efforts in the Region. The litigation, especially from the SEAR, up to 2017, that have facilitated SLT control or have been used by the tobacco industry to challenge an SLT control policy decision were reviewed. Most of the litigation related to SLT control from the Region are on pictorial health warnings. Bhutan has imposed a complete prohibition on sale, manufacture and import of all kinds of tobacco products and the litigation there relates to the prosecution of offenders for violating the ban. Judiciary in the Region is well informed about the ill-effects of tobacco use and remains positive to tobacco control initiatives in the interest of public health. In India, several SLT-specific litigation helped in better regulation of SLT products in the country. Litigation has compelled governments for effective enforcement of the domestic tobacco control laws and the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC). Parties to the WHO FCTC must now use Treaty Article 19 to strengthen their legal procedures and make the tobacco industry liable, for both criminal and civil wrongs.

Coincidental loss of DOCK8 function in NLRP10-deficient and C3H/HeJ mice results in defective dendritic cell migration.

Dendritic cells (DCs) are the primary leukocytes responsible for priming T cells. To find and activate naïve T cells, DCs must migrate to lymph nodes, yet the cellular programs responsible for this key step remain unclear. DC migration to lymph nodes and the subsequent T-cell response are disrupted in a mouse we recently described lacking the NOD-like receptor NLRP10 (NLR family, pyrin domain containing 10); however, the mechanism by which this pattern recognition receptor governs DC migration remained unknown. Using a proteomic approach, we discovered that DCs from Nlrp10 knockout mice lack the guanine nucleotide exchange factor DOCK8 (dedicator of cytokinesis 8), which regulates cytoskeleton dynamics in multiple leukocyte populations; in humans, loss-of-function mutations in Dock8 result in severe immunodeficiency. Surprisingly, Nlrp10 knockout mice crossed to other backgrounds had normal DOCK8 expression. This suggested that the original Nlrp10 knockout strain harbored an unexpected mutation in Dock8, which was confirmed using whole-exome sequencing. Consistent with our original report, NLRP3 inflammasome activation remained unaltered in NLRP10-deficient DCs even after restoring DOCK8 function; however, these DCs recovered the ability to migrate. Isolated loss of DOCK8 via targeted deletion confirmed its absolute requirement for DC migration. Because mutations in Dock genes have been discovered in other mouse lines, we analyzed the diversity of Dock8 across different murine strains and found that C3H/HeJ mice also harbor a Dock8 mutation that partially impairs DC migration. We conclude that DOCK8 is an important regulator of DC migration during an immune response and is prone to mutations that disrupt its crucial function.

Hep-2000 indirect immunofluorescence assay - an emerging screening tool for detection of antinuclear autoantibodies in various connective tissue disorders.

BACKGROUND: Connective tissue disorders (CTD's) are a group of autoimmune disorders having multifactorial etiology, multisystem involvement and overlapping clinical features. Their prevalence has been increasing in India, with Systemic lupus erythematosus (SLE) being the most common CTD, affecting mostly females. Antinuclear Antibodies (ANA) directed against a variety of nuclear antigens detectable in the serum are used for screening, diagnoses, and monitoring of autoimmune diseases, with immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA) being the most widely used methods. AIMS: 1.To evaluate the diagnostic significance of IFA in screening of Autoimmune CTDs. 2.To study different titres and patterns shown by ANA positive samples. MATERIALS AND METHODS: For IFA, patient's sera is incubated with substrate cells, and bound antibodies are detected by incubation with a dye-conjugated anti-human immunoglobulin which are visualized by fluorescent microscopy and different ANA titres and patterns were analysed. RESULTS: 57 samples were examined for ANA by Indirect IFA, of which 21 (36.8%) were ANA positive with a female preponderance (71.9%) in the peri-menopausal age group. Most common pattern reported was Speckled followed by Homogenous. The sensitivity & specificity of IIFA was found to be comparable with ELISA. CONCLUSION: CTD's are a group of autoimmune disorders with a plethora of clinical presentations, necessitating the need of a more specific and accurate screening test. ANA by IIFA gives patterns, which are associated with specific antibodies that help in reaching a diagnosis. ANA testing is a cost effective and non-invasive technique that can be used as a reliable screening test for Autoimmune disorders.

The severity of non-smoking chronic obstructive pulmonary disease is correlated with biomass fuel exposure and COPD assessment test score.

BACKGROUND AND OBJECTIVE: Tobacco smoking is an established risk factor for chronic obstructive pulmonary disease (COPD). Current evidence suggests that non-tobacco-related risk factors vary geographically and are less understood than smoking. This study aims to compare the risk factors, symptoms, and clinical features of smoking (S-COPD) and non-smoking (NS-COPD) in a COPD population. MATERIALS AND METHODS: In this retrospective cross-sectional study, 489 COPD patients were screened. Data on socio-demographics, smoking and medical history, other risk factors, symptoms, and clinical characteristics including COPD Assessment Test (CAT) score, and Modified Medical Research Council (mMRC) Dyspnea Scale were examined. RESULTS: Of the total selected 416 COPD patients, 35.34% were NS-COPD while 64.66% were S-COPD. S-COPD was predominant in males, whereas NS-COPD was predominant in females (P < 0.0001). In NS-COPD, biomass fuel exposure was a major risk factor (P < 0.0001), and 61% of subjects had a biomass fuel exposure index of >60. In bivariate and multivariate analyses, no risk factors were correlated with forced expiratory volume in 1 second (FEV1)% predicted, while among clinical features, duration of illness (P = 0.001) was correlated with lower values of FEV1 in the multivariate table of S-COPD. In the multivariate analysis, biomass fuel exposure (P = 0.039) and CAT score (P < 0.0001) were correlated with FEV1(%) in NS-COPD. CONCLUSION: Biomass fuel exposure is a substantial risk factor for NS-COPD and was correlated with FEV1(%) predicted. In addition, the CAT score correlated with disease severity in patients with NS-COPD. The development of COPD in non-smokers is being recognized as a separate phenotype and it should be managed according to risk factors.

Methylation of glycosylated sphingolipid modulates membrane lipid topography and pathogenicity of Cryptococcus neoformans.

In previous studies we showed that the replication of Cryptococcus neoformans in the lung environment is controlled by the glucosylceramide (GlcCer) synthase gene (GCS1), which synthesizes the membrane sphingolipid GlcCer from the C9-methyl ceramide. Here, we studied the effect of the mutation of the sphingolipid C9 methyltransferase gene (SMT1), which adds a methyl group to position 9 of the sphingosine backbone of ceramide. The C. neoformans Δsmt1 mutant does not make C9-methyl ceramide and, thus, any methylated GlcCer. However, it accumulates demethylated ceramide and demethylated GlcCer. The Δsmt1 mutant loses more than 80% of its virulence compared with the wild type and the reconstituted strain. Interestingly, growth of C. neoformans Δsmt1 in the lung was decreased and C. neoformans cells were contained in lung granulomas, which significantly reduced the rate of their dissemination to the brain reducing the onset of meningoencephalitis. Thus, using fluorescent spectroscopy and atomic force microscopy we compared the wild type and Δsmt1 mutant and found that the altered membrane composition and GlcCer structure affects fungal membrane rigidity, suggesting that specific sphingolipid structures are required for proper fungal membrane organization and integrity. Therefore, we propose that the physical structure of the plasma membrane imparted by specific classes of sphingolipids represents a critical factor for the ability of the fungus to establish virulence.

Spatiotemporal regulation of PKC via interactions with AKAP7 isoforms.

The regulation of kinases by scaffolding proteins greatly contributes to the fidelity of signal transduction. In the present study, we explored an interaction between the ubiquitous enzyme PKC (protein kinase C) and the scaffolding protein AKAP7 (A-kinase-anchoring protein 7). Using protein biochemistry and surface plasmon resonance approaches, we demonstrate that both AKAP7γ and AKAP7α are capable of high-affinity interactions with multiple isoenzymes of PKC. Furthermore, this interaction is achieved via multi-site binding on both proteins. FRET (fluorescence resonance energy transfer) analysis using a PKC activity reporter suggests that anchoring of the kinase within AKAP7 complexes enhances the phosphorylation of substrate proteins. Finally, we determined using FRAP (fluorescence recovery after photobleaching) and virtual modelling that AKAP7 restricts the mobility of PKC within cells by tethering it to subcellular compartments. Collectively, the results of the present study suggests that AKAP7 could play an integral role in dictating PKC localization and function in tissues where the two proteins are co-expressed.

Direct antimicrobial effects of chemokines on Cryptococcus spp, with special emphasis on a 'CXC' chemokine.

Cryptococcus species are ingenious human pathogens that are widespread globally. They continue to cause over 200,000 deaths per year. Presently due to the rise in resistance and therapy failure, it is necessary to shift the focus to an alternate therapeutic strategy against this pathogen. One promising approach is to emphasize the host defense system in order to develop more precise and customized treatment strategies. In this regard, research has revealed that interferon-γ-inducible CXCL10 chemokine, amongst other chemokines spanning both CXC and CC categories, has a direct killing effect in vitro against Cryptococcus neoformans and Cryptococcus gattii, with a significantly greater microbicidal effect against the former. Moreover, when CXCL10 is used in combination with CCL5, there is a significant reduction in the survival of C. gattii at normal-serum level concentration, indicating a previously unreported synergistic effect of these two chemokines. Confocal and STED microscopic studies have demonstrated that CXCL10 has both cell wall/membrane and intracellular targets against this fungus. These findings present new possibilities for developing chemokine-derived small molecule antifungals and may represent a step forward in creating precision medicine tailored to each patient.

Assessment of knowledge, attitude, and practice regarding intellectual property rights among medical, dental, and nursing professionals in a tertiary institution in Bhubaneswar City, Odisha: A cross-sectional survey.

BACKGROUND: To assess the knowledge, attitude, and practice (KAP) about intellectual property rights (IPRs) among medical, dental, and nursing students and faculties in a tertiary institute through cross-sectional survey in Bhubaneswar City, Odisha. MATERIALS AND METHODS: This study was a cross-sectional survey conducted from October to December, 2021 in a tertiary institution in Bhubaneswar city, Odisha. A self-structured, 29 close-ended questionnaires based on IPRs was used in the survey. The data obtained were tabulated and analyzed statistically using the Statistical Package for Social Sciences version 23.0. All the components of KAP were measured as absolute and relative frequencies. They were also assessed as mean and standard deviation. Descriptive analysis through frequency distribution was calculated and the Chi-square test was applied. The correlation between the domains was determined using Pearson's correlation coefficient. RESULT: A total of 489 participants participated in the survey, out of which 196 (40.1%) were males and 293 (59.9%) were females; 177 (36.2%) were interns, 147 (30.1%) were postgraduates, and 165 (33.7%) were faculties from all the three fields (medical, dental, and nursing). A total of 192 (39.3%) participants were from medical, 198 (40.5%) from dental, and 99 (20.2%) were from the nursing field. The mean KAP scores were significantly (P < 0.0001) higher among nursing interns respondents (2.963, 0.637, and 0.390), dental postgraduate respondents (2.213, 0.844, and 0.351), and dental faculties (1.953, 0.876, and 0.481). The mean knowledge score was significantly (P < 0.0001) greater among females than males and the mean attitude and practice scores were significantly (P < 0.0001) greater among males than females. Pearson's correlation coefficientwas found to be significant for knowledge-attitude, knowledge-practice domain. The values obtained were statistically significant. CONCLUSION: This study showed that more KAP was found in dental faculties, dental postgraduates, and nursing interns. However, the need to know IPR is still lacking among the healthcare professionals. Since IPR is the need of the hour and it has a potential ahead, it is necessary to include it in the curriculum so as to increase the knowledge about IPR among individuals, which will enable to creation of dynamic innovations in the near future.

Assessing knowledge, attitude, and readiness to use e-health among doctors in a tertiary health care unit in Bhubaneswar city, Odisha - A cross-sectional survey.

BACKGROUND: The term ""e-health"" refers to all technological applications in the delivery of a more affordable, high-speed, and widely accessible mode of health care. It is a definite solution to managing the public's health and well-being during the coronavirus disease (COVID-19) pandemic, and doctors from all fields of expertise are required to be at par with it in terms of knowledge, attitude, and readiness to use it to their advantage under the current circumstances. MATERIALS AND METHOD: A cross-sectional survey was conducted among the faculty, postgraduates, and interns of the medical and dental schools of a university, which used an expert-validated self-administered questionnaire assessing knowledge, attitude, and readiness to use e-health. RESULTS: Among the 400 participants, it was observed that the categories of age (P < 0.0001), gender (P = 0.018), designation (P = 0.031), and years of service (P < 0.0001) have significant differences across the groups. It was seen that the mean e-health knowledge (3.55 ± 0.52) and mean attitude (2.42 ± 0.59) to use e-health were more in dentists while participants from the medical field showed higher mean readiness (1.97 ± 0.58) to use e-health in daily practice. It was observed that male professionals had more mean knowledge (3.54 ± 0.60) than female professionals (3.43 ± 0.52) while female participants had more mean e-health readiness (1.96 ± 0.57). CONCLUSION: In a broad sense, the majority of participants responded positively to using e-health in their everyday practice. While medical doctors have a stronger outlook and preparedness, dentists showed more literacy and a supportive attitude to adopting e-health and telemedicine. Thus, it is necessary to step up comprehensive e-health workshops and training sessions for health care experts.

Pattern of Care and Outcomes of Gallbladder Cancer Patients: Retrospective Study from a High Incidence Region in India.

Lakhan KasyapIntroduction Gallbladder cancer (GBC) is the 20th most common cancer in India with a crude incidence rate of 2.3 per 100,000 persons. Of note, it is relatively common in states which fall in the Gangetic plains. Patients often present in the advanced stage and have an unfavorable prognosis. Materials and Methods From January to June 2021, 170 treatment-naive GBC (adenocarcinoma) patients who were registered at a tertiary care cancer center in North India, were included. Data were extracted from electronic medical records and was analyzed with SPSS. Results Median age was 56 years (range 32-77 years) and 65.5% ( n = 112) were female. Incidental GBC was found in 20% patient ( n = 34). Majority of patients (79.4%, n = 135) had preserved performance status. Advanced GBC was present in 85.8% ( n = 146) patients (locally advanced = 37.0% and metastatic = 48.8%). Biliary drainage procedure was performed in 24% of patients (68% of patients with obstructive jaundice). More than half of patients (53.5%) were lost to follow-up without any treatment. There were 33 patients (19.4%) who underwent surgery and 20 of them received neoadjuvant chemotherapy. Adjuvant chemotherapy and adjuvant radiotherapy were received by 13 and 2 patients, respectively. Palliative chemotherapy was administered to 46 patients. The most common chemotherapy regimen was gemcitabine-cisplatin. At a median follow-up of 1.7 months (95% confidence interval, 1-2.4 months), 42 patients (24%) progressed and 24 patients (14%) died, with 6 months estimated progression-free survival and overall survival being 60.2 and 79%, respectively. Conclusion GBC is an aggressive and lethal malignancy predominantly affecting females in the fifth decade with dismal outcomes. Improved access to health care, an aggressive approach in operable cases, and optimization of systemic and adjuvant therapy are the need of the hour.

Gestational Trophoblastic Neoplasia-A Retrospective Analysis of Patients Treated at a Tertiary Care Oncology Center in North India.

Anuj GuptaObjectives The aim of this study was to do a retrospective analysis of patients of gestational trophoblastic neoplasia (GTN) treated at our center concerning their clinical features and treatment outcomes. Materials and Methods Patients diagnosed and treated from May 2018 to December 2021 were included. All relevant information pertaining to eligible patients was retrieved from the electronic medical records. Patients were risk-stratified based on the World Health Organization (WHO) risk scoring system with a score of seven and above being classified into the high-risk category. Patients were monitored for response by measuring ß-human chorionic gonadotrophin (ß-HCG) levels before each consecutive cycle. Statistical Analysis Appropriate statistical analysis was performed using SPSS version 26. Results Records of 39 eligible patients were analyzed for clinical features out of which 38 were eligible for response assessment. The median age of presentation was 28 years with the majority of patients (79.4%) diagnosed based on ß-HCG levels and clinical history alone. The most common symptom was bleeding per vagina (64%), while the majority of antecedent pregnancies were abortions (59%). Of the 14 low-risk category patients, 12 received single-agent methotrexate/actinomycin D, while 2 received etoposide, methotrexate actinomycin D (EMACO) regimen. Overall response rates were 85.7% with the others responding to the second-line EMACO regimen. Five patients in this group had a WHO score of 5 or 6 and all of them responded to single-agent treatment. Among the 25 high-risk category patients, all received the EMACO regimen with high-dose methotrexate added to those with brain metastasis. The response rate was 87.5% with all the nonresponders having features of ultra-high risk of liver/brain metastasis and/or a WHO score of more than 12. While one nonresponder had expired despite treatment, the other two responded to the etoposide methotrexate and actinomycin D/ etoposide and cisplatin regimen. Conclusion Our results are in consonance with other reported studies. The subcategories of low-risk GTN with a WHO score of 5 and 6 and high-risk GTN with ultra-high-risk features deserve further research in the form of multicenter prospective studies.

Lipid signalling in pathogenic fungi.

In recent years, the study of lipid signalling networks has significantly increased. Although best studied in mammalian cells, lipid signalling is now appreciated also in microbial cells, particularly in yeasts and moulds. For instance, microbial sphingolipids and their metabolizing enzymes play a key role in the regulation of fungal pathogenicity, especially in Cryptococcus neoformans, through the modulation of different microbial pathways and virulence factors. Another example is the quorum sensing molecule (QSM) farnesol. In fact, this QSM is involved not only in mycelial growth and biofilm formation of Candida albicans, but also in many stress related responses. In moulds, such as Aspergillus fumigatus, QSM and sphingolipids are important for maintaining cell wall integrity and virulence. Finally, fungal cells make oxylipins to increase their virulence attributes and to counteract the host immune defences. In this review, we discuss these aspects in details.

Congenital granular cell tumor: Report of a case with literature review and differential diagnosis.

Congenital granular cell tumor (CGCT) is a rare benign lesion and presents as a fibrous mass arising from the alveolus in the newborn. The prenatal screening of lesions can help in parent counseling, determining the complications, as larger size lesions may interfere with normal delivery and require a cesarean section.

A long-standing case of desmoplastic fibroblastoma of the face.

The present case report depicts an unusually large desmoplastic fibroblastoma. The diagnosis of the lesion appears to be deceptive clinically. The purpose of this case image is to highlight its size and presenting symptoms, which could easily be mistaken for an odontogenic, salivary gland, or a soft tissue neoplasm.

Advancements in diagnostic techniques for oral cancer detection.

Oral malignancy is among the highest prevalent malignancies all over the world. In comparison to systemic malignancies such as lung cancer and colon cancer, they are frequently overlooked by the general public. Nevertheless, they can be exceedingly lethal if left ignored, regardless at the early stage of the condition. Dentists are the finest qualified healthcare specialists in this sector and are responsible for detecting benign and potentially malignant oral conditions such as oral cancers. Oral carcinoma's high prevalence and delayed appearance are serious international medical concerns. Early detection and management of oral carcinoma are the key goals of the World Health Organization (WHO). The identification of key clinical manifestations during the preliminary oral examination can enhance the patient's likelihood of living. Unfortunately, the conventional technology's practical value is limited by a number of drawbacks. Current advancements in optical scanning techniques, such as tissue-fluorescence imaging and optical coherence tomography, have proven to be quite effective. In particular, nanoparticle-based immunosensors, genomics, and salivary biomarkers, epigenetics and microarray have all received a lot of attention. Raising awareness about frequent dental examinations and using noninvasive, effective, and cost-effective screening tools would improve initial stage detection of oral carcinoma and improve patients' longevity.