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Introduction: Charcot arthropathy is a myriad of osseous degenerative changes that can affect theoretically any joint of the body. The pathophysiology of this condition is based on microtrauma, leading to the deterioration of articular nerves. The most common cause in the upper extremity is syringomyelia., Case Report: A 64-year-old male patient presented with painless right wrist swelling and deformity. His radiographs showed degenerative changes in radiocarpal and intercarpal joints. Magnetic resonance imaging of the brain and cervical spine demonstrated Type II Chiari malformation and syringomyelia, and neurological evaluation revealed myelopathy., Conclusion: Charcot arthropathy of the wrist, an exceedingly rare condition, is a diagnosis of exclusion. The common causes of arthritis of the wrist such as Rheumatoid arthritis and tuberculosis must be ruled out. When a patient presents with wrist Charcot arthropathy thorough neurological examination must be done. Diabetes mellitus, tabes dorsalis, and leprosy are the other frequently cited causes that must be looked for., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

With technology development, the growing self-communicating devices in IoT networks require specific naming and identification, mainly provided by IPv6 addresses. The IPv6 address in the IoT network is generated by using the stateless auto address configuration (SLAAC) mechanism, and its uniqueness is ensured by the DAD protocol. Recent research suggests that IPv6 deployment can be a risky decision due to the existing SLAAC-based addressing scheme and the DAD protocol being prone to reconnaissance and denial of service (DoS) attacks. This research paper proposes a new IPv6 generation scheme with an improved secure DAD mechanism to address these problems. The proposed addressing scheme generates IPv6 addresses by taking a hybrid approach based on vendor id of medium access control (MAC) address, physical location, and arbitrary random numbers, which mitigates reconnaissance attacks by malicious nodes. To prevent the DAD process from DoS attacks, hybrid values of interface identifier (IID) are multicast instead of actual values. The proposed scheme is evaluated under reconnaissance and DoS attacks in the presence of malicious nodes. The evaluation results demonstrate that the proposed method effectively mitigates reconnaissance and DoS attacks, outperforming the EUI-64 and SEUI-64 schemes in terms of address success rate (ASR), energy consumption, and communication overhead. Specifically, the proposed method significantly reduces the average probing rate for scanning the existence of an IPv6 address, with only a 1% probing rate compared to SEUI-64's 5% and EUI-64's 100%. Furthermore, the additional communication overhead introduced by the proposed method is less than 13% and 11% compared to EUI-64 and SEUI-64, respectively. Additionally, the energy consumption required to assign an IPv6 address using the proposed method is lower by 12% and 5% when compared to EUI-64 and SEUI-64, respectively. These findings highlight the effectiveness of the proposed method in enhancing security and optimizing resource utilization in IPv6 addressing., (© 2024. The Author(s).)

Sugar signaling forms the basis of metabolic activities crucial for an organism to perform essential life activities. In plants, sugars like glucose, mediate a wide range of physiological responses ranging from seed germination to cell senescence. This has led to the elucidation of cell signaling pathways involving glucose and its counterparts and the mechanism of how these sugars take control over major hormonal pathways such as auxin, ethylene, abscisic acid and cytokinin in Arabidopsis. Plants use HXK1(Hexokinase) as a glucose sensor to modulate changes in photosynthetic gene expression in response to high glucose levels. Other proteins such as SIZ1, a major SUMO E3 ligase have recently been implicated in controlling sugar responses via transcriptional and translational regulation of a wide array of sugar metabolic genes. Here, we show that these two genes work antagonistically and are epistatic in controlling responsiveness toward high glucose conditions.

Monosodium glutamate (MSG), a sodium salt derived from glutamic acid, is widely used in commercial food products to improve taste, quality, and preservation. However, its consumption may have detrimental effects on male reproductive function. Nevertheless, plant extracts, such as Lepidium meyenii (Maca), Trigonella foenum-graecum (Fenugreek), Spirulina platensis (Spirulina), and Tribulus arabica (Tribulus), may ameliorate these adverse effects. To this effect, the phytochemical properties of Lepidium meyenii , Trigonella foenum-graecum , Spirulina platensis , and Tribulus arabica were assessed, and their potential impact on MSG-induced impairment of reproductive parameters was examined. The phytochemical composition (steroids, terpenes, phenols, flavonoids) of the plants was profiled through spectrophotometry and the antioxidant activity was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. Thirty-six male Wistar rats were divided into six groups at random: a control group receiving distilled water, and five experimental groups (MSG, Maca, Fenugreek, Spirulina, and Tribulus) receiving 900 mg/kg/day of MSG dissolved in water for 45 days. Subsequently, the animals in the experimental groups were administered 500 mg/kg/day of the respective plant extract via oral gavage for an additional 35 days, while the MSG group continued to receive water only. Following the treatment period, the animals were sacrificed, and their reproductive tract organs were collected, weighed, and subjected to further analysis. Phytochemical analysis revealed the presence of diverse bioactive elements in the plant extracts, including phenolic and flavonoid compounds. Exposure to MSG negatively impacted total and progressive sperm motility, which was ameliorated by Lepidium meyenii treatment. Sperm morphology showed no significant differences among groups. Treatment of the phytochemical agents diminished histomorphometric alternations of the testicular length, germinal epithelium height, and number of cells in seminiferous tubules, which were caused by the initial administration of MSG. Testosterone and LH levels were reduced in the MSG group but improved in extract-treated groups. The study suggests Lepidium meyenii as a potential remedy for reproductive dysfunction. However, further investigation into its mechanisms and human safety and efficacy is warranted.

Phlebectasia of the internal jugular vein (IJV) is an unusual vascular anomaly, particularly in paediatric patients. Here, we present a case of IJV phlebectasia of a girl in her early childhood, highlighting its clinical presentation, diagnostic workup and management. The patient presented with a painless, non-pulsatile neck mass, which was identified as an enlarged IJV on imaging studies. Since it is a benign condition, and the patient is asymptomatic, observation with regular monitoring is advised., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Taenia solium , like other helminthic parasites, lacks key components of cellular machinery required for endogenous lipid biosynthesis. This deficiency compels the parasite to obtain all of its lipid requirements from its host. The passage of lipids across the cell membrane is tightly regulated. To facilitate effective lipid transport, the cestode parasite utilizes certain lipid binding proteins called FABPs. These FABPs bind with the lipid ligands and allow the transport of lipids across the membranes and into the cytosol. Here, by integrating a computational with homology protein prediction tools, we had identified five FABPs in the T. solium proteome. We confirmed their presence by RNA expression analysis of respective genes from the parasite's cysticerci transcript. During the molecular modeling and MD simulation studies, two of them, TsM_000544100 and TsM_001185100, were most stable. Furthermore, they had a robust interaction with the IgG1 molecule, as evidenced by MD simulation. In addition, by employing in silico screening, we had identified potential ligand interacting residues that are present on the probable druggable site. In combination with in vitro cysticidal assays, enalaprilat dihydrate showed efficacy against cysticerci, which suggests that FABPs play a significant role in the cysticercus life cycle. Together, we provided a detailed distribution of all FABPs expressed by T. solium cysticerci and the critical role of TsM_001185100 in cysticercus viability., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The excretory-secretory proteome plays a pivotal role in both intercellular communication during disease progression and immune escape mechanisms of various pathogens including cestode parasites like Taenia solium. The cysticerci of T. solium causes infection in the central nervous system known as neurocysticercosis (NCC), which affects a significant population in developing countries. Extracellular vesicles (EVs) are 30-150-nm-sized particles and constitute a significant part of the secretome. However, the role of EV in NCC pathogenesis remains undetermined. Here, for the first time, we report that EV from T. solium larvae is abundant in metabolites that can negatively regulate PI3K/AKT pathway, efficiently internalized by macrophages to induce AKT and mTOR degradation through auto-lysosomal route with a prominent increase in the ubiquitination of both proteins. This results in less ROS production and diminished bacterial killing capability among EV-treated macrophages. Due to this, both macro-autophagy and caspase-linked apoptosis are upregulated, with a reduction of the autophagy substrate sequestome 1. In summary, we report that T. solium EV from viable cysts attenuates the AKT-mTOR pathway thereby promoting apoptosis in macrophages, and this may exert immunosuppression during an early viable stage of the parasite in NCC, which is primarily asymptomatic. Further investigation on EV-mediated immune suppression revealed that the EV can protect the mice from DSS-induced colitis and improve colon architecture. These findings shed light on the previously unknown role of T. solium EV and the therapeutic role of their immune suppression potential., (© 2024 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Cell cycle involves the sequential and reiterative progression of important events leading to cell division. Progression through a specific phase of the cell cycle is under the control of various factors. Since the cell cycle in multicellular eukaryotes responds to multiple extracellular mitogenic cues, its study in higher forms of life becomes all the more important. One such factor regulating cell cycle progression in plants is sugar signalling. Because the growth of organs depends on both cell growth and proliferation, sugars sensing and signalling are key control points linking sugar perception to regulation of downstream factors which facilitate these key developmental transitions. However, the basis of cell cycle control via sugars is intricate and demands exploration. This review deals with the information on sugar and TOR-SnRK1 signalling and how they manoeuvre various events of the cell cycle to ensure proper growth and development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rawat and Laxmi.)

The new and evolving paradigms of psychiatric disorders pathogenesis are deeply inclined toward chronic inflammation that leads to disturbances in the neuronal networks of patients. A strong association has been established between the inflammation and neurobiology of depression which is mediated by different toll-like receptors (TLRs). TLRs and associated signalling pathways are identified as key immune regulators to stress and infections in neurobiology. They are a special class of transmembrane proteins, which are one of the broadly studied members of the Pattern Recognition Patterns family. This review focuses on summarizing the important findings on the role of TLRs associated with psychotic disorders and acquired epilepsy. This review also shows the promising potential of TLRs in immune response mediated through antidepressant therapies and TLRs polymorphism associated with various psychotic disorders. Moreover, this also sheds light on future directions to further target TLRs as a therapeutic approach for psychiatric disorders., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction Orthodontic diagnosis and treatment planning encounter distinctive complexities when dealing with cleft lip and palate anomalies. This research endeavors to thoroughly examine skeletal and dental characteristics through cephalometric analyses among individuals with bilateral cleft lip and palate (BCLP) within the central Indian population. Due to anatomical variations and growth constraints, traditional cephalometric mean values derived from standard population studies are often inadequate for these cases. Advanced technology, such as NemoCeph (Nemotech, Madrid, Spain) software, enhances measurement accuracy. Methods Fifty patients, including 25 with BCLP and 25 without BCLP, aged 10 to 18, were selected for this cross-sectional study. Lateral cephalograms were traced and analyzed using NemoCeph software. Skeletal and dental parameters were measured, and a comparison was made between BCLP patients and the general population. Statistical analysis was conducted using the Student's unpaired t-test. Both SPSS Statistics Version 24.0 (IBM Corp., Armonk, NY, USA) and GraphPad Prism Version 7.0 (GraphPad Software, San Diego, CA, USA) were used for data analysis. Results The investigation revealed significant disparities across several parameters, including sella-nasion-A point angle (SNA), sella-nasion-B point angle (SNB), A point-nasion-B point angle (ANB), the inter-incisal angle (the angle between the long axes of the upper and lower incisors), and UP 1 to A-pog (a specific vertical measurement between anatomical markers labeled "upper 1" and "A point to pogonion"), with associated p-values for the skeletal and dental parameters of 0.310, 0.259, 0.195, 0.0001, and 0.0001, respectively. A comparison between manual tracing and digital methods indicated a reduction in errors and an improvement in measurement precision. Notably, patients diagnosed with BCLP exhibited distinctive skeletal and dental traits, highlighting the necessity for tailored treatment approaches. Conclusion This study emphasizes the importance of personalized cephalometric evaluations for patients with BCLP. Standard mean values may not be applicable due to unique anatomical considerations in these cases. Advanced technology and patient-specific assessments are crucial for accurate diagnosis, treatment planning, and orthognathic procedures in individuals with cleft lip and palate conditions. Embracing digital tools and tailored approaches can enhance patient care quality and lead to better clinical outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Rawat et al.)

Breast cancer (BC) is one of the most common types of cancer in women in the United Arab Emirates. Immunogenic tumours, such as triple-negative breast cancer (TNBC), show increased neutrophil infiltration, which is associated with poor prognosis and limited efficacy of immunotherapy. This study aims to investigate in vitro the bidirectional effect of neutrophils on metastatic TNBC (MDA-MB-231) compared to less-metastatic luminal breast cancer (MCF-7) cell lines. We found that BC cells or their conditioned medium (CM) reduced the viability of neutrophil-like cells (HL60). This was supported by increased cellular stress and NETosis in differentiated HL60 cells (dHL60) upon exposure to MDA-MB-231 compared to MCF-7-CM using nucleic acid staining essays. Flow cytometry showed comparable expression of inflammatory markers by polymorphonuclear cells (PMN) when treated with MDA-MB-231-CM and standard polarizing cocktails. Furthermore, MDA-MB-231-CM triggered an inflammatory pattern with evidence of stronger adhesion (CD62L) and degranulation (CD11b and CD66b) phenotypes. The proinflammatory polarization of dHL60 by MDA-MB-231-CM was additionally confirmed by the elevated CD54 expression, myeloperoxidase, and CD11b protein levels, which matched an increased transwell migratory capacity. In conclusion, BC might use neutrophils to their benefit through NETosis and complement system activation, which makes this crosstalk a potential mechanism for understanding tumour progression.

Intrathoracic extraskeletal Ewing's sarcoma (EES) is a relatively uncommon malignant tumour. Here, we present a scenario involving an adult man in his 20s with a large intrathoracic EES that manifested as a lung abscess. Preoperative diagnostic tests were inconclusive; hence, the patient underwent an exploratory thoracotomy for the excision of the mass. Histopathology revealed a small round blue cell tumour, and immunohistochemistry, along with fluorescence in situ hybridisation, confirmed the diagnosis of Ewing's sarcoma. Adjuvant chemoradiotherapy was recommended, but the patient did not comply. A year later, he presented with a recurrence of the intrathoracic mass and subsequently received adjuvant chemotherapy. Currently, he is in remission., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Helminth infections are a global health menace affecting 24% of the world population. They continue to increase global disease burden as their unclear pathology imposes serious challenges to patient management. Neurocysticercosis is classified as neglected tropical disease and is caused by larvae of helminthic cestode Taenia solium. The larvae infect humans and localize in central nervous system and cause NCC; a leading etiological agent of acquired epilepsy in the developing world. The parasite has an intricate antigenic make-up and causes active immune suppression in the residing host. It communicates with the host via its secretome which is complex mixture of proteins also called excretory secretory products (ESPs). Understanding the ESPs interaction with host can identify therapeutic intervention hot spots. In our research, we studied the effect of T. solium ESPs on human macrophages and investigated the post-translation switch involved in its immunopathogenesis., Methodology: T. solium cysts were cultured in vitro to get ESPs and used for treating human macrophages. These macrophages were studied for cellular signaling and miR expression and quantification at transcript and protein level., Conclusion: We found that T. solium cyst ESPs treatment to human macrophages leads to activation of Th2 immune response. A complex cytokine expression by macrophages was also observed with both Th1 and Th2 cytokines in milieu. But, at the same time ESPs modulated the macrophage function by altering the host miR expression as seen with altered ROS activity, apoptosis and phagocytosis. This leads to activated yet compromised functional macrophages, which provides a niche to support parasite survival. Thus T. solium secretome induces Th2 phenomenon in macrophages which may promote parasite's survival and delay their recognition by host immune system., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Arora et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Metacestode, the larva of Taenia solium, is the causative agent for neurocysticercosis (NCC), which causes epilepsy. The unavailability of a vaccine against human NCC is a major cause for its widespread prevalence across the globe. Therefore, the development of a reliable vaccine against NCC is the need of the hour. Employing a combination of proteomics and immunoinformatics, we endeavored to formulate a vaccine candidate. The immune reactive cyst fluid antigens of T. solium were identified by immune-blotting two-dimensional gels with NCC patient's sera, followed by Matrix-assisted laser desorption-ionization analysis. We performed a detailed proteomic study of these immune reactive proteins by utilizing immune-informatics tools, identified the nontoxic, nonallergic, B-cell epitopes, and collected epitopes with the least sequence homology with human and other Taenia species. These epitopes were joined through linkers to construct a multiepitope vaccine. Different physiochemical parameters such as molecular weight (23.82 kDa), instability (39.91), and aliphatic index (49.61) were calculated to ensure the stability of the linked peptides vaccine. The vaccine demonstrated stable interactions with different immune receptors like Toll-like receptor 4 and IgG confirming that it will effectively stimulate the host immune response. We anticipate that our designed B-cell linear epitope-based vaccine will show promising results in in vitro and in vivo assays. This study provides a platform that would be useful to develop other suitable vaccine candidates to prevent helminthic neglected tropical diseases in near future., (© 2023 Wiley Periodicals LLC.)

Background: Helicobacter pylori is a prominent causative agent of gastric ulceration, gastric adenocarcinoma and gastric lymphoma and have been categorised as a group 1 carcinogen by WHO. The treatment of H. pylori with proton pump inhibitors and antibiotics is effective but also leads to increased antibiotic resistance, patient dissatisfaction, and chances of reinfection. Therefore, an effective vaccine remains the most suitable prophylactic option for mass administration against this infection., Results: We modelled a multi-chimera subunit vaccine candidate against H. pylori by screening its secretory/outer membrane proteins. We identified B-cell, MHC-II and IFN-γ-inducing epitopes within these proteins. The population coverage, antigenicity, physiochemical properties and secondary structure were evaluated using different in-silico tools, which showed it can be a good and effective vaccine candidate. The 3-D construct was predicted, refined, validated and docked with TLRs. Finally, we performed the molecular docking/simulation and immune simulation studies to validate the stability of interaction and in-silico cloned the epitope sequences into a pET28b(+) plasmid vector., Conclusion: The multiepitope-constructed vaccine contains T- cells, B-cells along with IFN-γ inducing epitopes that have the property to generate good cell-mediated immunity and humoral response. This vaccine can protect most of the world's population. The docking study and immune simulation revealed a good binding with TLRs and cell-mediated and humoral immune responses, respectively. Overall, we attempted to design a multiepitope vaccine and expect this vaccine will show an encouraging result against H. pylori infection in in-vivo use., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Allergic bronchopulmonary aspergillosis (ABPA) frequently complicates asthma. There is urgent need to develop evidence-based guidelines for the management of ABPA in children. The Evidence Based Guideline Development Group (EBGDG) of the Indian Academy of Pediatrics (IAP) National Respiratory Chapter (NRC) addressed this need., Methods: The EBGDG shortlisted clinical questions relevant to the management of ABPA in asthma. For each question, the EBGDG undertook a systematic, step-wise evidence search for existing guidelines, followed by systematic reviews, followed by primary research studies. The evidence was collated, critically appraised, and synthesized. The EBGDG worked through the Evidence to Decision (EtD) framework, to formulate recommendations, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Results: Seven clinical questions were prioritized, and the following recommendations formulated. (1) Children with poorly controlled asthma should be investigated for ABPA (conditional recommendation, moderate certainty of evidence). (2) Low dose steroid therapy regimen (0.5 mg/kg/d for the first 2 wk, followed by a progressive tapering) is preferable to higher dose regimens (conditional recommendation, very low certainty of evidence). (3) Oral steroid regimens longer than 16 wk (including tapering), should not be used (conditional recommendation, very low certainty of evidence). (4) Antifungals may or may not be added to steroid therapy as the evidence was neither in favour nor against (conditional recommendation, low certainty of evidence). (5) For clinicians using antifungal agents, the EBGDG recommends against using voriconazole instead of itraconazole (conditional recommendation, very low certainty of evidence). (6) No evidence-based recommendation could be framed for using pulse steroid therapy in preference to conventional steroid therapy. (7) Immunotherapy with biologicals including omalizumab or dupilumab is not recommended (conditional recommendation, very low certainty of evidence)., Conclusions: This evidence-based guideline can be used by healthcare providers in diverse clinical settings., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Competing Interests: The authors report no conflict of interest.

Statins have been shown to cause diverse male reproductive function impairment, and in some cases, orchialgia. Therefore, the current study investigated the possible mechanisms through which statins may alter male reproductive parameters. Thirty adult male Wistar rats (200-250 g) were divided into three groups. The animals were orally administered rosuvastatin (50 mg/kg), simvastatin (50 mg/kg), or 0.5% carboxy methyl cellulose (control), for a 30-day period. Spermatozoa were retrieved from the caudal epididymis for sperm analysis. The testis was used for all biochemical assays and immunofluorescent localization of biomarkers of interest. Rosuvastatin-treated animals presented with a significant decrease in sperm concentration when compared to both the control and simvastatin groups ( p < 0.005). While no significant difference was observed between the simvastatin and the control group. The Sertoli cells, Leydig cells and whole testicular tissue homogenate expressed transcripts of solute carrier organic anion transporters ( SLCO1B1 and SLCO1B3 ). There was a significant decrease in the testicular protein expression of the luteinizing hormone receptor, follicle stimulating hormone receptor, and transient receptor potential vanilloid 1 in the rosuvastatin and simvastatin-treated animals compared to the control. The expression of SLCO1B1 , SLCO1B2 , and SLCO1B3 in the different spermatogenic cells portray that un-bio transformed statin can be transported into the testicular microenvironment, which can subsequently alter the regulation of the gonadal hormone receptors, dysregulate pain-inflammatory biomarkers, and consequently impair sperm concentration.

This study aimed to review the existing literature to investigate the potential link between early-life antibiotic use and being overweight or obese in children. PubMed, Web of Science, Embase, Google Scholar, and Cochrane Library were searched to identify studies published until August 2021 that assessed the relationship between early-childhood antibiotic use and measures of body mass index. The studies included children aged 0-18 years. Only cohort studies were taken into consideration. Studies published in languages other than English were excluded. Antibiotic usage in early life may increase the risk of obesity in children and the addition of yeast probiotics, such as Saccharomyces boulardii CNCM I 745 , to antibiotic prescription can serve as a potential option to mitigate this risk., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2023, Rawat et al.)

Aims: Development of anticancer agents targeting tubulin protein., Background: Tubulin protein is being explored as an important target for anticancer drug development. Ligands binding to the colchicine binding site of the tubulin protein act as tubulin polymerization inhibitors and arrest the cell cycle in the G2/M phase., Objective: Synthesis and screening of benzotriazole-substituted 2-phenyl quinazolines as potential anticancer agents., Methods: A series of benzotriazole-substituted quinazoline derivatives have been synthesized and evaluated against human MCF-7 (breast), HeLa (cervical) and HT-29 (colon) cancer cell lines using standard MTT assays., Results: ARV-2 with IC 50 values of 3.16 μM, 5.31 μM, 10.6 μM against MCF-7, HELA and HT29 cell lines, respectively displayed the most potent antiproliferative activities in the series while all the compounds were found non-toxic against HEK293 (normal cells). In the mechanistic studies involving cell cycle analysis, apoptosis assay and JC-1 studies, ARV-2 and ARV-3 were found to induce mitochondria-mediated apoptosis., Conclusion: The benzotriazole-substituted 2-phenyl quinazolines have the potential to be developed as potent anticancer agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Colchicine binding site represent a crucial target for the anticancer drug development especially in view of emerging drug resistance from the currently available chemotherapeutics. A total of 16 novel 4-N-heterocyclic-2-aryl-6,7,8-trimethoxyquinazolines were synthesized and screened for antiproliferative and tubulin polymerization inhibition potential. The synthesized compounds were evaluated against MCF-7, HeLa and HT-29 cancer cell lines and normal cell line HEK-293 T. In the series, 2‑aryl group with 4‑bromophenyl substitution displayed IC 50 values of 6.37 µM, 17.43 µM, 6.76 µM and 4‑chlorophenyl substitution displayed IC 50 values of 2.16 µM, 8.53 µM, 10.42 µM against MCF-7, HELA and HT29 cancer cell lines, respectively. In the mechanistic studies involving cell cycle analysis, apoptosis assay and JC-1 studies, both the lead compounds were found to induce mitochondria mediated apoptosis and lead molecule with 4‑chlorophenyl substitution displayed significant tubulin polymerization inhibition activity. In the computation studies, lead molecule displayed significant binding affinites in the colchicine domain and showed good thermodynamic stability during 100 ns MD simulation studies. 4-N-Heterocyclic-2-aryl-6,7,8-trimethoxyquinazolines showed appreciable drug like characteristics and can be developed as potent anticancer agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

To combat the problem of acaricide resistance in ticks, efforts have been made to develop eco-friendly herbal acaricides which are safe for animal use with no possibilities of evoking environment and residual toxicity. In the present study, the acaricidal properties of a commonly available plant, Annona squamosa have been established to develop a novel antitick phytoformulation using leaf extract, suitable solvents and emulsifier for managing resistant tick infestations in animals. The quality control of the safe and stable phytoformulation using Rutin as a major constituent was maintained by HPTLC profiling. Several phytformulations (A-E) were prepared and formulation 'C' is identifried as the most effective showing 52.5-75% antitick activity against in vitro treated resistant strains of R. microplus (IVRI-IV and V) with 33.8-40.2% inhibition of oviposition while 65-85% mortality against multiacaricide resistant field populations. The phytoformulation provided 70.4% efficacy after first larval challenge in experimentally infested animals. The field efficacy of the formulation in different multilocational field trials was 68.53-77.8%. The detail antitick efficacy of the formulation along with safety and stability are explained as a component of antitck technology to manage resistant tick problem in livestock., (Copyright © 2022. Published by Elsevier B.V.)

Subepithelial fibrosis is a characteristic hallmark of airway remodeling in asthma. Current asthma medications have limited efficacy in treating fibrosis, particularly in patients with severe asthma, necessitating a deeper understanding of the fibrotic mechanisms. The NF-κB pathway is key to airway inflammation in asthma, as it regulates the activity of multiple pro-inflammatory mediators that contribute to airway pathology. Bcl10 is a well-known upstream mediator of the NF-κB pathway that has been linked to fibrosis in other disease models. Therefore, we investigated Bcl10-mediated NF-κB activation as a potential pathway regulating fibrotic signaling in severe asthmatic fibroblasts. We demonstrate here the elevated protein expression of Bcl10 in bronchial fibroblasts and bronchial biopsies from severe asthmatic patients when compared to non-asthmatic individuals. Lipopolysaccharide (LPS) induced the increased expression of the pro-fibrotic cytokines IL-6, IL-8 and TGF-β1 in bronchial fibroblasts, and this induction was associated with the activation of Bcl10. Inhibition of the Bcl10-mediated NF-κB pathway using an IRAK1/4 selective inhibitor abrogated the pro-fibrotic signaling induced by LPS. Thus, our study indicates that Bcl10-mediated NF-κB activation signals increased pro-fibrotic cytokine expression in severe asthmatic airways. This reveals the therapeutic potential of targeting Bcl10 signaling in ameliorating inflammation and fibrosis, particularly in severe asthmatic individuals.

Severe asthma and lung cancer are both heterogeneous pathological diseases affecting the lung tissue. Whilst there are a few studies that suggest an association between asthma and lung cancer, to the best of our knowledge, this is the first study to identify common genes involved in both severe asthma and lung cancer. Publicly available transcriptomic data for 23 epithelial brushings from severe asthmatics and 55 samples of formalin-fixed paraffin-embedded (FFPE) lung cancer tissue at relatively early stages were analyzed by absolute gene set enrichment analysis (GSEA) in comparison to 37 healthy bronchial tissue samples. The key pathways enriched in asthmatic patients included adhesion, extracellular matrix, and epithelial cell proliferation, which contribute to tissue remodeling. In the lung cancer dataset, the main pathways identified were receptor tyrosine kinase signaling, wound healing, and growth factor response, representing the early cancer pathways. Analysis of the enriched genes derived from the pathway analysis identified seven genes expressed in both the asthma and lung cancer sets: BCL3 , POSTN , PPARD , STAT1 , MYC , CD44 , and FOSB . The differential expression of these genes was validated in vitro in the cell lines retrieved from different lung cancer and severe asthma patients using real-time PCR. The effect of the expression of the seven genes identified in the study on the overall survival of lung cancer patients ( n = 1925) was assessed using a Kaplan-Meier plot. In vivo validation performed in the archival biopsies obtained from patients diagnosed with both the disease conditions provided interesting insights into the pathogenesis of severe asthma and lung cancer, as indicated by the differential expression pattern of the seven transcripts in the mixed group as compared to the asthmatics and lung cancer samples alone.

Designing a vaccine against a pathogen has been the toughest challenge to fight against any infectious diseases. To overcome this problem, use of artificial neural network with immuno-informatics is emerging as a front runner solution. For a successful designing of a potent vaccine, prediction of T-cell/B-cell epitopes, antigen processing and presentation analysis, antigenic potential analysis of epitopes, usages of linkers, population coverage, codon optimization, allergenicity assessment, toxicity prediction of construct, and finally protein-peptide docking for stability of vaccine are important steps. To achieve this, several bioinformatics software, tools and online web servers have been developed for each application, which have their own advantages and limitations. Scientists must evaluate these parameters and should take the decision to apply more suitable and precise servers for each analysis and prediction based on their accuracy, suitability, and robustness., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Ascaris lumbricoides infects 80 million people per year, causing malnutrition, stunted growth of children etc., but there is no vaccine available against it. We aimed to design a multimeric-subunit vaccine using comprehensive immunoinformatic approach., Research Design and Methods: The T and B cell epitopes were shortlisted on antigenicity, allergenicity, and toxicity from proteome data and joined with appropriate linkers. The physical characteristics of vaccine candidate was calculated and docking/molecular dynamic simulation performed to validate its robustness. The multimeric protein was codon optimized and in-silico cloned in pET28b., Results: From the 23,604 proteins of Ascaris, we filtered based on epitope prediction, localization, antigenicity, and allergenicity. Prepared a vaccine of 534 amino acid long, 56.31 kD weight and pI 4.52. Physiochemical features showed it is soluble, highly antigenic and non-allergenic. Its tertiary structure was forecasted, certified, and refined. The immunoinformatic simulation studies showed it to be potent T and B cell stimulator., Conclusions: We identified highly antigenic peptides of Ascaris from its proteome with good potential to induce innate as well as humoral immune response. These peptides were used to design a chimeric vaccine against Ascariasis infection, which can be used for prophylactic purpose but needs experimental and clinical validation.

Introduction: Taenia solium infection is among the 17 most neglected tropical diseases identified by World Health Organization and to be eradicated by 2030. This parasite infects the central nervous system (Neurocysticercosis [NCC]) and intestine [Taeniasis]). NCC is the most frequent cause of acquired epilepsy in endemic regions and Taeniasis is responsible for the widespread malnutrition and abdominal discomfort among children. Epilepsy caused by T. solium is preventable and the total elimination of NCC can be achieved by good hygiene, mass therapy, and most importantly vaccination of pigs or humans. Vaccine for pig is available but not widely in use and for humans it's still elusive., Area Covered: Several vaccine candidates for porcine cysticercosis have been tried like TSOL18, SP3Vac, KETc7, TSOL45, etc. with good success in the limited field trial. This review highlights some seminal contributions for the anti-cestode vaccine, the associated challenges, current status, suggestive future directions, and the need of vaccine for human use., Expert Opinion: Though several vaccines are available, none is being widely used due to lack of awareness, economic constraints, accessibility, etc. Hence, there is a need for a newer, economic, and reliable vaccine for humans or pigs use to reduce the disease burden.

Serotonin is a neurotransmitter that plays a crucial role in the regulation of several behavioral and cognitive functions by binding to a number of different serotonin receptors present on the cell surface. We report here the synthesis and characterization of several novel fluorescent analogs of serotonin in which the fluorescent NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl) group is covalently attached to serotonin. The fluorescent ligands compete with the serotonin 1A receptor specific radiolabeled agonist for binding to the receptor. Interestingly, these fluorescent ligands display a high environmental sensitivity of their fluorescence. Importantly, the human serotonin 1A receptor stably expressed in CHO-K1 cells could be specifically labeled with one of the fluorescent ligands with minimal nonspecific labeling. Interestingly, we show by spectral imaging that the NBD-labeled ligand exhibits a red edge excitation shift (REES) of 29 nm when bound to the receptor, implying that it is localized in a restricted microenvironment. Taken together, our results show that NBD-labeled serotonin analogs offer an attractive fluorescent approach for elucidating the molecular environment of the serotonin binding site in serotonin receptors. In view of the multiple roles played by the serotonergic systems in the central and peripheral nervous systems, these fluorescent ligands would be useful in future studies involving serotonin receptors.

The present investigation demonstrates a green and scalable chemical approach to prepare aminoborate-functionalized reduced graphene oxide (rGO-AmB) for aqueous lubricants. The chemical, structural, crystalline, and morphological features of rGO-AmB are probed by XPS, FTIR, Raman, XRD, and HRTEM measurements. The spectroscopic analyses revealed the multiple interaction pathways between rGO and AmB. rGO-AmB exhibited long-term dispersion stability and improved the thermal conductivity of water by 68%. The thermal conductivity increased with increasing concentration of rGO-AmB and temperature. rGO-AmB as an additive to water (0.2%) enhanced the tribological properties of a steel tribopair under the boundary lubrication regime by the significant reduction in friction (70%) and wear (68%). The tribo-induced gradual deposition of an rGO-AmB-based thin film facilitated the interfacial sliding between the steel tribopair and protected it from the wear. The ultralow thickness, excellent dispersibility in water, high thermal conductivity, intrinsic low frictional properties, and good affinity toward the tribo-interfaces make rGO-AmB a potential candidate for aqueous lubricants.

Safe blood transfusion being the cornerstone of any Blood Transfusion Services requires meticulous testing for Transfusion Transmitted Disease (TTD) markers in donated blood. We performed head-to-head comparison of ELISA and ECLIA for detection of TTD markers for Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV) in 10,164 Indian blood donors. All concordant reactive, discordant reactive and concordant non-reactive samples were re-confirmed using Individual Donor-Nucleic Acid Amplification Test (ID-NAT) as the 'gold standard' test. 223 samples were found reactive; out of which 93 (four HIV, 34 HCV and 55 HBV) samples were concordant reactive and tested positive by both methods while 130 discordant reactive samples were reactive either by ELISA or ECLIA. Out of 130 discordant reactive samples ELISA-reactive and ECLIA-non-reactive samples for HIV, HCV and HBV were 15, eight, and 29 respectively while ECLIA-reactive ELISA-non-reactive samples for HIV, HCV and HBV were 39, 36 and three respectively. Sensitivity of ECLIA and ELISA was 100 % for all three TTD markers, while specificity was 99.62 % and 99.85 % for HIV; 99.64 % and 99.84 % for HCV and 99.97 % and 99.70 % for HBV respectively. Strength of agreement and Kappa Statistics for ECLIA and ELISA compared to the gold standard test was poor and fair for HIV (k = 0.169 and 0.347), moderate and good for HCV (k = 0.539 and 0.763), and very good and good for HBV (k = 0.973 and 0.783). According to this study, it can be concluded both the testing techniques; ELISA and ECLIA have 100 % sensitivity for the detection for HBV, HCV and HIV in blood donors and therefore, either can be used for TTD screening in blood banks in India., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Neurocysticercosis (NCC) is infection by cestode Taenia solium/pork tapeworm. Sero-diagnosis of NCC is still a challenge. Radiological imaging (CT/MRI) are cost intensive, requires technical expertise and resource intensive. Hence, its availability is restricted in endemic zone. Existing Enzyme electro immune transfer blot (EITB) antigens are difficult to make and is not standardized for endemic population. Therefore, there is a definite need for easy and reliable EITB tool., Methods: T. solium metacestode were harvested from naturally infected swine post slaughter. The cyst fluid/vesicular fluid was aspirated and processed with ultracentrifugation and immune blot was performed with this antigen., Results: A total of 406 cases [rural 256 (NCC 78, seizures other than NCC 108 and healthy controls 70); urban 150 (NCC 41, seizures other than NCC 59 and healthy controls 50)] were enrolled. Positive EITB (detection of band <50 kDa) was significantly associated with NCC patients of urban population only (p < 0.001) but not in rural populations (p = 0.292). However, identification of 15 kDa band had significant association with NCC both in urban and rural populations with overall sensitivity of 91.5% and specificity of 91.6%. Presence of 35 kDa band was associated with multiple NCC (p < 0.001). The study shows that 15 kDa reactive band on EITB is highly sensitive and specific for diagnosis of NCC in endemic population., Conclusions: Presence of 35 kDa band on EITB was associated with infection by multiple cysticerci. The observations demand purification of cyst fluid antigens to develop simple and easy to execute test in field studies., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ternary bismuth halides are interesting functional materials closely related to Pb halide perovskite photovoltaic material, and are widely sought after due to reduced toxicity of Bi compared to Pb. There are several reports on synthesis of Cs₃Bi₂Br 9 nanocrystals (NCs) due to its being relatively stable compared to lead perovskite. Cs₃Bi₂Br 9 nanocrystals have been synthesised using benzoyl bromide as an precursor using hot injection process at two different temperatures of 120 °C and 160 °C. Samples have been characterized for its structural, optical, microstructural and luminescent properties using X-ray diffraction, (XRD) UV-Vis spectroscopy, high resolution transmission electron microscopy and photoluminescent spectroscopy. XRD showed formation of Cs₃Bi₂Br 9 phase with mono-crystalline structure. UV-Vis showed two types of band gap in the visible region which shows that the material can be used for photovoltaic applications. HRTEM confined the particles to be composed of nanocrystals with ˜5 nm particles in the samples grown at 120 °C and it the particles joined together yield various structures composed of nanoparticles. The time resolved photoluminescence shows average life times of 3.067 ns and 4.761 ns for samples grown at two different temperatures. To the best of our knowledge, this is the first report where benzoyl halide has been used as alternative precursor for the synthesis of lead free double perovskite Cs₃Bi₂Br 9 nanocrystals which have many applications.