Mannose-Binding Lectin Gene Variants as Disease Susceptibility Biomarkers in Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease characterized by progressive destruction of peripheral joints. About 1% of the human population worldwide is suffering from this disease. The pathophysiology of RA is largely being influenced by immune dysregulation. Mannose-binding lectin (MBL), an acute-phase protein, has been reported to play an important role in pathogenesis of RA by the activation of complement pathway. Various studies documented the established the role of MBL in pathogenesis of various autoimmune diseases, including RA. MBL protein is encoded by gene MBL2, mapped on chromosome 10q11.2-q21. Objective: Both MBL serum levels and activity are mainly determined genetically by its variants. So considering the putative clinical role of MBL2, this case-control association study was designed to assess its six functional variants in a northwestern Indian cohort. Methods: Genetic typing of six MBL2 variants was done by amplification refractory mutation system-polymerase chain reaction. Data were analyzed using suitable statistical tools. Results: Significant difference has been observed in genotypic and allelic distribution between cases and controls for rs11003125. Comparison of allelic distribution for rs1800450 showed significantly high prevalence of A allele in cases than controls. Conclusion: These results indicate that MBL2 variants may act as plausible marker for susceptibility toward RA. Keeping this in view, it is pertinent to screen these variants in other population groups of India.

Point-of-care ultrasound (POCUS) in the surgery of a paraplegic pregnant female: A case of "do no harm".

We present here a case of multidisciplinary management of a 20-year-old pregnant woman who presented with sudden paraplegia attributed to a large paraspinal tumor. Magnetic resonance imaging (MRI) revealed compressive dorsal myelopathy due to an extramedullary tumor. Given the urgency of her symptoms and pregnancy status, a multidisciplinary team decided to proceed with surgery while avoiding radiation exposure (eg, O/C-arm). Intraoperative point-of-care ultrasound (POCUS) was utilized for tumor localization and surgical guidance, facilitating successful gross total excision with minimal risk to the fetus. Postoperative recovery was uneventful, with improvement in muscle strength and preservation of the pregnancy. Beyond tumor localization, POCUS offers additional benefits in assessing maternal hemodynamics and detecting potential complications. This case highlights the utility of POCUS as a radiation-free theranostic imaging modality in pregnant patients with spinal tumors, enhancing safety in surgery and optimizing outcomes for both mother and fetus.

A case report on multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection.

Key Clinical Message: Early recognition and treatment of Multisystem Inflammatory Syndrome in Children (MIS-C) within the context of COVID-19 infection is crucial for improved outcomes. Prompt intervention with IVIG and steroids leads to significant improvement in a severe case of MIS-C. Clinicians should be vigilant for MIS-C symptoms and initiate timely management. Abstract: We report a case involving a fourteen-year-old male with COVID-19 infection who developed multisystem inflammatory disease. A previously healthy child presented with a history of 10 days of fever and cough, along with diarrhea, and vomiting for 3 days. His COVID-19 infection was confirmed through Polymerase Chain Reaction (PCR), and the laboratory values were remarkable for high levels of C-reactive protein, D-dimers, B-type natriuretic peptide (BNP), and troponin I. He developed circulatory shock on the second day of the presentation and needed inotropic support. Steroids and intravenous immunoglobulin (IVIG) were started in light of Multisystem Inflammatory Syndrome in Children (MIS-C), which improved his condition. Thus, during the management of COVID-19 infection, early detection and a careful clinical characterization for MIS-C are essential.

Current Status and Emerging Trends in Colorectal Cancer Screening and Diagnostics.

Colorectal cancer (CRC) is a prevalent and potentially fatal disease categorized based on its high incidences and mortality rates, which raised the need for effective diagnostic strategies for the early detection and management of CRC. While there are several conventional cancer diagnostics available, they have certain limitations that hinder their effectiveness. Significant research efforts are currently being dedicated to elucidating novel methodologies that aim at comprehending the intricate molecular mechanism that underlies CRC. Recently, microfluidic diagnostics have emerged as a pivotal solution, offering non-invasive approaches to real-time monitoring of disease progression and treatment response. Microfluidic devices enable the integration of multiple sample preparation steps into a single platform, which speeds up processing and improves sensitivity. Such advancements in diagnostic technologies hold immense promise for revolutionizing the field of CRC diagnosis and enabling efficient detection and monitoring strategies. This article elucidates several of the latest developments in microfluidic technology for CRC diagnostics. In addition to the advancements in microfluidic technology for CRC diagnostics, the integration of artificial intelligence (AI) holds great promise for further enhancing diagnostic capabilities. Advancements in microfluidic systems and AI-driven approaches can revolutionize colorectal cancer diagnostics, offering accurate, efficient, and personalized strategies to improve patient outcomes and transform cancer management.

Association of mannose binding lectin with chronic obstructive pulmonary disease susceptibility and its clinical outcomes.

BACKGROUND: The physiological interactions of MBL suggest its contribution towards the pathogenesis of COPD. OBJECTIVE: The present case-control study was undertaken to elucidate the role of MBL with COPD risk and clinical outcomes in north Indian cohort. METHODS: Patients were enrolled as per GOLD criteria. MBL2 variants were selected based on the literature and their putative functional significance. Genotyping of six single nucleotide polymorphisms of MBL2 comprising of two coding (rs1800450, rs1800451) and four non-coding variants (rs11003125, rs7096206, rs11003123 and rs7095891) was done by using PCR-RFLP and ARMS-PCR. Serum MBL levels were analysed by sandwich ELISA. RESULTS: Overall findings of the molecular genetic analysis of MBL2 indicated significant difference in frequency of three of the six studied variants, between patients and controls or among different disease severity stages. Heterozygous genotype of rs7095891 showed significant protective association towards severity of disease. Linkage disequilibrium (LD) analysis indicated a strong LD between rs1800450 and rs7095891 while intermediate LD was observed for rs11003123/rs11003125 and rs7096206/rs11003125. Haplotype analysis revealed 17.14-fold risk of developing exacerbations conferred by GGGTGG haplotype. Significantly low serum MBL levels observed in COPD patients as compared to controls. Significant difference in MBL deficiency levels were also observed for homozygous wild and variant genotypes of rs11003125 and rs7096206 respectively, as well as for all genotypes of rs11003123 than respective controls. CONCLUSION: The present study reinforces the role played by MBL in the susceptibility, protection and clinical outcomes of COPD. Therefore, including the reported associations at diagnostic, prognostic and therapeutic interventions may prove helpful.

Quality-by-design-based development of ultradeformable nanovesicular transgelosome of standardized Piper longum extract for melanoma.

Background: Melanoma is the most aggressive and deadly form of skin cancer. The stratum corneum of the skin is a major obstacle to dermal and transdermal drug delivery. Ultradeformable nanovesicular transferosome has the capacity for deeper skin penetration and its incorporation into hydrogel forms a transgelosome that has better skin permeability and patient compliance. Method: Here, the quality-by-design-based development and optimization of nanovesicular transgelosome of standardized Piper longum fruit ethanolic extract (PLFEE) for melanoma therapy are reported. Results: Compared with standardized PLFEE-loaded plain gel, the transgelosome displayed optimal pharmaceutical properties and improved ex vivo skin permeability and in vivo tumor regression in B16F10 melanoma-bearing C57BL/6 mice. Conclusion: The results reflect the potential of transgelosome for melanoma therapy.

Melanoma is a deadly form of skin cancer that originates from melanocytes in the skin. Skin is a major barrier to drug delivery. Transferosome is a liquid nanoformulation that has the capacity for deeper skin penetration. The transferosome was prepared from standardized Piper longum fruit ethanolic extract (PLFEE) and loaded into gel to form a transgelosome for improved skin application and patient compliance. Compared with extract-loaded plain gel, the transgelosome showed good pharmaceutical properties with better activity in melanoma (B16F10)-bearing female C57BL/6 mice. The therapeutic activity of the standard anticancer drug dacarbazine was improved with the prepared PLFEE transgelosome.

Transfer learning-driven ensemble model for detection of diabetic retinopathy disease.

In this study, we propose an ensemble model for the detection of diabetic retinopathy (DR) illness that is driven by transfer learning. Due to diabetes, the DR is a problem that affects the eyes. The retinal blood vessels in a person with high blood sugar deteriorate. The blood arteries may enlarge and leak as a result, or they may close and stop the flow of blood. If DR is not treated, it can become severe, damage vision, and eventually result in blindness. Medical experts study the colored fundus photos for this reason in order to manually diagnose disease, however this is a perilous technique. As a result, the condition was automatically identified utilizing retinal scans and a number of computer vision-based methods. A model is trained on one task or datasets employing the transfer learning (TL) technique, and then the pre-trained models or weights are applied to another task or dataset. Six deep learning (DL)-based convolutional neural network (CNN) models were trained in this study using huge datasets of reasonable photos, including DenseNet-169, VGG-19, ResNet101-V2, Mobilenet-V2, and Inception-V3. We also applied a data-preprocessing strategy to improve the accuracy and lower the training costs in order to improve the results. The experimental results demonstrate that the suggested model works better than existing approaches on the same dataset, with an accuracy of up to 98%, and detects the stage of DR.

Quality by design-based development and optimization of fourth-generation ternary solid dispersion of standardized Piper longum extract for melanoma therapy.

The study aimed to enhance the solubility, dissolution, and oral bioavailability of standardized Piper longum fruits ethanolic extract (PLFEE) via fourth-generation ternary solid dispersion (SD) for melanoma therapy. With the use of solvent evaporation method, the standardized PLFEE was formulated into SD, optimized using Box-Wilson's central composite design (CCD), and evaluated for pharmaceutical performance and in vivo anticancer activity against melanoma (B16F10)-bearing C57BL/6 mice. The optimized SD showed good accelerated stability, high yield, drug content, and content uniformity for bioactive marker piperine (PIP). The X-ray diffraction (XRD), differential scanning calorimetry (DSC), polarized light microscopy (PLM), and selected area electron diffraction (SAED) analysis revealed its amorphous nature. The attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and high-performance thin layer chromatography (HPTLC) revealed the compatibility of excipients with the PLFEE. The contact angle measurement and in vitro dissolution study revealed excellent wetting of SD and improved dissolution profile as compared to the plain PLFEE. The in vivo oral bioavailability of SD reflected a significant (p < 0.05) improvement in bioavailability (Frel = 188.765%) as compared to plain extract. The in vivo tumor regression study revealed the improved therapeutic activity of SD as compared to plain PLFEE. Further, the SD also improved the anticancer activity of dacarbazine (DTIC) as an adjuvant therapy. The overall result revealed the potential of developed SD for melanoma therapy either alone or as an adjuvant therapy with DTIC.

Bioengineered dual fluorescent carbon nano dots from Indian long pepper leaves for multifaceted environmental and health utilities.

In this article, we present the synthesis of Piper longum leaves-derived ethanolic carbon dots (PLECDs) using the most simplistic environmentally friendly solvothermal carbonization method. The PLECDs fluoresced pink color with maximum emission at 670 nm at 397 nm excitation. Additionally, the dried PLECDs dissolved in water showed green fluorescence with higher emission at 452 nm at 370 nm excitation. The UV spectra showed peaks in the UV region (271.25 nm and 320.79 nm) and a noticeable tail in the visible region, signifying the efficient synthesis of nano-sized carbon particles and the Mie scattering effect. Various functional groups (-OH, -N-H, -C-H, -C = C, -C-N, and -C-O) were identified using Fourier transform infrared spectroscopy (FTIR). Its nanocrystalline property was revealed by the sharp peaks in the X-ray diffraction (XRD). High-resolution transmission electron microscopy (HRTEM) photomicrograph displayed a roughly spherical structure with a mean size of 2.835 nm. The energy dispersive X-ray (EDAX) and X-ray photoelectron spectroscopy (XPS) revealed the elemental abundance of C, O, and N. The high-performance thin-layer chromatography (HPTLC) fingerprint of PLECDs showed an altered pattern than its precursor (Piper longum leaves ethanolic extract or PLLEE). The PLECDs sensed Cu2+ selectively with a limit of detection (LOD) and limit of quantification (LOQ) of 0.063 µM and 0.193 µM, respectively. It showed excellent cytotoxicity toward MDA-MB-231 (human breast cancer), SiHa (human cervical carcinoma), and B16F10 (murine melanoma) cell lines with excellent in vitro bioimaging outcomes. It also has free radical scavenging activity. The PLECDs also showed outstanding bacterial biocompatibility, pH-dependent fluorescence stability, photostability, physicochemical stability, and thermal stability.

Chemometric-Based Analysis of Metabolomics Studies of Bioactive Fractions of Pleurotus osteratus and Their Correlation with In Vitro Anti-Cancer Activity.

Richness in nutrients with an ample of the myco-bioactive molecules makes Pleurotus osteratus preferential mushroom. In this paper, we conducted a preliminary study on bio-assay-guided fractionation of dichloromethane:ethanol crude extract (1:1, v/v) of P. osteratus (CD) against human breast cancer cell line (MDA-MB-231). Later, CD and its potent hexane (H) and ethyl acetate (EA) fraction were screened against a panel of a human cancer cell lines. H fraction possesses higher cytotoxicity followed by EA and CD. Literature review revealed that polyphenol and ergosterol are the biomarkers found in P. osteratus and could responsible for its cytotoxic potential. Accordingly, hyphenated liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based polyphenol and ergosterol-targeted myco-metabolite profiling of CD, H, and EA fractions were carried out. Despite being significantly rich in polyphenol and ergosterol content, EA fraction showed moderate cytotoxicity. Considering this, liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF/MS)-based untargeted myco-metabolite profiling of CD, H and EA fractions was further conducted to identify a new biomarker. Tentatively, 20 myco-metabolites were identified, belonging to the class of steroids, alkaloid, terpenoid, fatty alcohol, and polyketide. The myco-metabolite variabilities among potent samples in correlation to their in vitro anti-cancer activity was explored using the different chemometric tools: principal component analysis (PCA), hierarchical clustering analysis (HCA), and partial least square (PLS). A probable synergistic action among identified myco-metabolites (betulin, solanocapsine, ophiobolin F, linoleoyl ethanolamide, (13R,14R)-7-labdene-13,14,15-triol, asterosterol, cholest-5-ene, (3b,6b,8a,12a)-8,12-epoxy-7(11)-eremophilene-6,8,12-trimethoxy-3-ol, beta-obscurine, myxalamid B, momordol, and avocadyne 4-acetate) may be responsible for the observed cytotoxicity potential of H fraction of P. osteratus.

Tracing the Anti-cancer Mechanism of Pleurotus osteratus by the Integrative Approach of Network Pharmacology and Experimental Studies.

The present study identified the probable mechanism behind the anti-cancer activity of the hexane fraction of Pleurotus osteratus (HFPO) using network pharmacology and experimental validation. HFPO myco-metabolites targets and targets related to the cancer were mined from the online web server, and overlapping targets were screened. Out of the 74 overlapping targets, 33 targets were identified in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of cancer. Furthermore, the main active myco-metabolites and hub targets were identified by network analysis of the compound-targets network and protein-protein interaction (PPI), respectively. Molecular docking results showed good binding affinity of the hub targets with their respective myco-metabolites. HFPO induced in-vitro anti-cancer activity by affecting the PI3K-AKT-mTOR pathway, besides time-dependent cell cytotoxicity and apoptotic cell body formation. Additionally, tumor volume reduction was observed in HFPO-treated Ehrlich ascites carcinoma (EAC) bearing Swiss albino mice. Overall, HFPO induces anti-cancer potential by modulating the PI3K-AKT-mTOR signaling pathway.