Buffalo-bur (Solanum rostratum Dunal) invasiveness, bioactivities, and utilization: a review.

Solanum rostratum Dunal, belongs to the Solanaceae family and has drawn attention for its intricate interplay of invasiveness, phytochemical composition, and potential bioactivities. Notably invasive, S. rostratum employs adaptive mechanisms during senescence, featuring thorn formation on leaves, fruits, and stems seed self-propulsion, and resistance to drought. This adaptability has led to its proliferation in countries such as China, Canada, and Australia, extending beyond its Mexican origin. Despite its invasive historical reputation, recent studies unveil a rich array of phytochemicals in S. rostratum, suggesting untapped economic potential due to under-exploration. This review delves into exploring the potential uses of S. rostratum while elucidating the bioactive compounds associated with diverse identified bioactivities. In terms of phytochemistry, S. rostratum reveals an abundance of various bioactive compounds, including alkaloids, flavonoids, phenols, saponins, and glycosides. These compounds confer a range of beneficial bioactivities, encompassing antioxidant, antifungal, anticarcinogenic, anti-inflammatory, phytotoxic, and pesticidal properties. This positions S. rostratum as a reservoir of valuable chemical constituents with potential applications, particularly in medicine and agriculture. The review provides comprehensive insights into the phytochemistry, bioactivities, and bioactivity-guided fractionation of S. rostratum. In this review, we focus on the potential utilization of S. rostratum by emphasizing its phytochemical profile, which holds promise for diverse applications. This review is the first that advocates for further exploration and research to unlock the plant's full potential for both economic and environmental benefit.

Diabetes and the fabkin complex: A dual-edged sword.

The Fabkin complex, composed of FABP4, ADK, and NDPKs, emerges as a novel regulator of insulin-producing beta cells, offering promising prospects for diabetes treatment. Our approach, which combines literature review and database analysis, sets the stage for future research. These findings hold significant implications for both diabetes treatment and research, as they present potential therapeutic targets for personalized treatment, leading to enhanced patient outcomes and a deeper comprehension of the disease. The multifaceted role of the Fabkin complex in glucose metabolism, insulin resistance, anti-inflammation, beta cell proliferation, and vascular function underscores its therapeutic potential, reshaping diabetes management and propelling advancements in the field.

Hesperidin Supplementation Improves Altered PON -1, LDL Oxidation, Inflammatory Response and Hepatic Function in an Experimental Rat Model of Hyperlipidemia.

In this study, we have examined the effect of hesperidin on rats fed on an experimental high-fat diet. Male Wistar rats were given a high-fat diet orally for one month for developing an HFD (High fat- diet) model. Rats were also supplemented with hesperidin (100 mg/kg body weight) for one month. We determined serum LDL (Low-density lipoprotein) oxidation, Paraoxonase-1 (PON-1) activity, and histopathological profile of the liver. Inflammatory cytokines levels were also measured in serum. HFD induced significant changes in LDL oxidation and PON-1 activity. Liver tissue histopathology and gene expression of inflammatory markers (Il-6(Interleukin-6), TNF- alpha (Tumor necrosis factor alpha), NF-KB (Nuclear factor kappa B) show that significant changes occur in the hyperlipidemic model of rats. We also show that hesperidin can effectively improve plasma antioxidant, LDL oxidation, and inflammatory cytokine expression in rats already subjected to hyperlipidemic stress. We conclude that hesperidin may protect the liver from oxidative stress by improving hepatic function.

Addressing comprehensive complexities a striking familial hypercholesterolemia case study.

BACKGROUND: Premature aortic involvement and comprehensive management strategies in familial hypercholesterolemia familial hypercholesterolemia (FH), a rare autosomal dominant genetic disorder, poses significant challenges due to its propensity for elevated low-density lipoprotein cholesterol, premature coronary heart disease, and vascular atherosclerosis. CASE PRESENTATION: Unraveling Cardiovascular Complexities: A Striking Familial Hypercholesterolemia. This case study delves into a remarkable instance of FH in a 16-year-old female who presented with chest pain and worsening dyspnea. Diagnostic evaluation revealed distinct electrocardiographic changes, elevated troponin levels, and profound dyslipidemia. Remarkable findings on transthoracic echocardiography, computed tomography angiography, and catheterization prompted multidisciplinary interventions and demonstrated remarkable enhancements in ventricular function, mitral regurgitation, and aortic stenosis. CONCLUSION: The case study underscores the urgency of comprehensive management strategies in confronting the myriad challenges of FH, emphasizing the value of early intervention, innovative therapies, and rigorous imaging modalities for unraveling the intricate cardiovascular manifestations of this condition.

Compact rover surveying and laser scanning for BIM development.

This paper presents a custom made small rover based surveying, mapping and building information modeling solution. Majority of the commercially available mobile surveying systems are larger in size which restricts their maneuverability in the targeted indoor vicinities. Furthermore their functional cost is unaffordable for low budget projects belonging to developing markets. Keeping in view these challenges, an economical indigenous rover based scanning and mapping system has developed using orthogonal integration of two low cost RPLidar A1 laser scanners. All the instrumentation of the rover has been interfaced with Robot Operating System (ROS) for online processing and recording of all sensorial data. The ROS based pose and map estimations of the rover have performed using Simultaneous Localization and Mapping (SLAM) technique. The perceived class 1 laser scans data belonging to distinct vicinities with variable reflective properties have been successfully tested and validated for required structural modeling. Systematically the recorded scans have been used in offline mode to generate the 3D point cloud map of the surveyed environment. Later the structural planes extraction from the point cloud data has been done using Random Sampling and Consensus (RANSAC) technique. Finally the 2D floor plan and 3D building model have been developed using point cloud processing in appropriate software. Multiple interiors of existing buildings and under construction indoor sites have been scanned, mapped and modelled as presented in this paper. In addition, the validation of the as-built models have been performed by comparing with the actual architecture design of the surveyed buildings. In comparison to available surveying solutions present in the local market, the developed system has been found faster, accurate and user friendly to produce more enhanced structural results with minute details.

Identification of hub genes in calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is a heart valve disorder characterized primarily by calcification of the aortic valve, resulting in stiffness and dysfunction of the valve. CAVD is prevalent among aging populations and is linked to factors such as hypertension, dyslipidemia, tobacco use, and genetic predisposition, and can result in becoming a growing economic and health burden. Once aortic valve calcification occurs, it will inevitably progress to aortic stenosis. At present, there are no medications available that have demonstrated effectiveness in managing or delaying the progression of the disease. In this study, we mined four publicly available microarray datasets (GSE12644 GSE51472, GSE77287, GSE233819) associated with CAVD from the GEO database with the aim of identifying hub genes associated with the occurrence of CAVD and searching for possible biological targets for the early prevention and diagnosis of CAVD. This study provides preliminary evidence for therapeutic and preventive targets for CAVD and may provide a solid foundation for subsequent biological studies.

Antigen-Clustered Nanovaccine Achieves Long-Term Tumor Remission by Promoting B/CD 4 T Cell Crosstalk.

Current cancer vaccines using T cell epitopes activate antitumor T cell immunity through dendritic cell/macrophage-mediated antigen presentation, but they lack the ability to promote B/CD4 T cell crosstalk, limiting their anticancer efficacy. We developed antigen-clustered nanovaccine (ACNVax) to achieve long-term tumor remission by promoting B/CD4 T cell crosstalk. The topographic features of ACNVax were achieved using an iron nanoparticle core attached with an optimal number of gold nanoparticles, where the clusters of HER2 B/CD4 T cell epitopes were conjugated on the gold surface with an optimal intercluster distance of 5-10 nm. ACNVax effectively trafficked to lymph nodes and cross-linked with BCR, which are essential for stimulating B cell antigen presentation-mediated B/CD4 T cell crosstalk in vitro and in vivo. ACNVax, combined with anti-PD-1, achieved long-term tumor remission (>200 days) with 80% complete response in mice with HER2+ breast cancer. ACNVax not only remodeled the tumor immune microenvironment but also induced a long-term immune memory, as evidenced by complete rejection of tumor rechallenge and a high level of antigen-specific memory B, CD4, and CD8 cells in mice (>200 days). This study provides a cancer vaccine design strategy, using B/CD4 T cell epitopes in an antigen clustered topography, to achieve long-term durable anticancer efficacy through promoting B/CD4 T cell crosstalk.

Short-term patency of iliofemoral to tibial bypass with vascular allografts in a minority population: A retrospective analysis of a single center acute care facility.

OBJECTIVE: The aim of this study was to examine the short-term patency rates and associated factors of open lower limb, iliofemoral to tibial bypass using cryopreserved saphenous vein (CSV) in a minority population at an acute care hospital in New York City. METHODS: A retrospective analysis of patients undergoing infra-inguinal bypass from iliofemoral vessels to tibial arteries with CSV between March 2020-April 2022 at an acute care facility (Harlem Hospital Center, Harlem, New York) was performed. Data including patient demographics, comorbidities, type of operation, follow-up surveillance, and salvage procedures were collected. Results were presented in patency line graphs and a life table. Target limb revascularization (TLR) and amputation free survival (AFS) were also calculated. RESULTS: Eleven bypass procedures were included in the analysis. Patients were followed for a mean of 10.8 months. Cumulative primary patency rates at 1, 6, and 12 months were 72.7%, 54.5%, and 40.9%, respectively. TLR was 36.4% and the AFS was 66.67% at the mean 10.8-month follow-up. CONCLUSIONS: The patency rates of minority patients undergoing bypass with CSV were analyzed with creation of a life table and calculation of patency rates, TLR and AFS. The short-term primary patency rates and post-operative outcomes were found to be comparable to larger studies in non-minority cohorts. These results suggest that larger studies as well as prospective analyses and randomized controlled trials in this patient cohort and demographic are needed, as well as optimal selection of patients to determine true clinical implications.

Factors Affecting the Early Maturation of Arteriovenous Fistulae Created at a Tertiary Centre in Oman.

Objectives: This study aimed to determine the risk factors associated with the failure of arteriovenous fistulae (AVF) maturation. Methods: This retrospective cohort study was conducted from January 2014 to December 2018 in Sultan Qaboos University Hospital, Muscat, Oman. Patients were followed-up 3 months after surgery, and their electronic medical records were accessed for demographic and clinical data. Univariate analysis was used to determine the risk factors associated with early AVF maturation and multivariant analysis was used to determine the predictive factors for AVF failure. Results: A total of 269 patients were included. Female gender was a significant factor affecting AVF maturity (P = 0.049), while age (P = 0.626), diabetes (P = 0.954), hypertension (P = 0.378), dyslipidaemia (P = 0.907), coronary artery disease (P = 0.576), cerebrovascular accident (P = 0.864), congestive heart failure (P = 0.685), previous central venous catheterisation (P = 0.05), fistula type (P = 0.863) and fistula site (P = 0.861) did not affect AVF maturation. Binary logistic regression showed that all the risk factors were insignificant. Failure of early AVF maturation affected 11.5% in the cohort. Conclusion: This study found that the proportion of early AVF maturation at our hospital is at par with that in the international literature. Failure of AVF maturation was significantly associated with the female gender. These findings can help nephrologists and vascular surgeons prognosticate AVF maturation rates. However, a larger study is needed for definitive conclusions.

Targeting NF-κB signaling cascades of glioblastoma by a natural benzophenone, garcinol, via in vitro and molecular docking approaches.

Glioblastoma multiforme (GBM) is regarded as the most aggressive form of brain tumor delineated by high cellular heterogeneity; it is resistant to conventional therapeutic regimens. In this study, the anti-cancer potential of garcinol, a naturally derived benzophenone, was assessed against GBM. During the analysis, we observed a reduction in the viability of rat glioblastoma C6 cells at a concentration of 30 µM of the extract (p < 0.001). Exposure to garcinol also induced nuclear fragmentation and condensation, as evidenced by DAPI-stained photomicrographs of C6 cells. The dissipation of mitochondrial membrane potential in a dose-dependent fashion was linked to the activation of caspases. Furthermore, it was observed that garcinol mediated the inhibition of NF-κB (p < 0.001) and decreased the expression of genes associated with cell survival (Bcl-XL, Bcl-2, and survivin) and proliferation (cyclin D1). Moreover, garcinol showed interaction with NF-κB through some important amino acid residues, such as Pro275, Trp258, Glu225, and Gly259 during molecular docking analysis. Comparative analysis with positive control (temozolomide) was also performed. We found that garcinol induced apoptotic cell death via inhibiting NF-κB activity in C6 cells, thus implicating it as a plausible therapeutic agent for GBM.

An Update on Emergent Nano-Therapeutic Strategies against Pediatric Brain Tumors.

Pediatric brain tumors are the major cause of pediatric cancer mortality. They comprise a diverse group of tumors with different developmental origins, genetic profiles, therapeutic options, and outcomes. Despite many technological advancements, the treatment of pediatric brain cancers has remained a challenge. Treatment options for pediatric brain cancers have been ineffective due to non-specificity, inability to cross the blood-brain barrier, and causing off-target side effects. In recent years, nanotechnological advancements in the medical field have proven to be effective in curing challenging cancers like brain tumors. Moreover, nanoparticles have emerged successfully, particularly in carrying larger payloads, as well as their stability, safety, and efficacy monitoring. In the present review, we will emphasize pediatric brain cancers, barriers to treating these cancers, and novel treatment options.

Peptide-Drug Conjugates: Design, Chemistry, and Drug Delivery System as a Novel Cancer Theranostic.

The emergence of peptide-drug conjugates (PDCs) that utilize target-oriented peptide moieties as carriers of cytotoxic payloads, interconnected with various cleavable/noncleavable linkers, resulted in the key-foundation of the new era of targeted therapeutics. They are capable of retaining the integrity of conjugates in the blood circulatory system as well as releasing the drugs at the tumor microenvironment. Other valuable advantages are specificity and selectivity toward targeted-receptors, higher penetration ability, and drug-loading capacity, making them a suitable candidate to play their vital role as promising carrier agents. In this review, we summarized the types of cell-targeting (CTPs) and cell-penetrating peptides (CPPs) that have broad applications in the advancement of targeted drug-delivery systems (DDS). Moreover, the techniques to overcome the limitations of peptide-chemistry for their extensive implementation to construct the PDCs. Besides this, the diversified breakthrough of linker chemistry, and ample knowledge of various cytotoxic payloads used in PDCs in recent years, as well as the mechanism of action of PDCs was critically discussed. The principal aim is to provide scattered and diversified knowledge in one place and to help researchers understand the pinching knots in the science of PDC development, also their progression toward a bright future for PDCs as novel theranostics in clinical practice.

Monosodium Glutamate Even at Low Dose May Affect Oxidative Stress, Inflammation and Neurodegeneration in Rats.

Monosodium glutamate (MSG) is a widely used flavour enhancer. A daily intake of MSG at high dosage (2000-4000 mg/kg body weight) is reported to be toxic to humans and experimental animals. The present study aims to investigate the toxic effect of oral administration of MSG at low concentrations (30 and 100 mg/kg body weight) by evaluating biochemical parameters of oxidative stress and inflammation in blood; expression of neuroinflammatory gene and histopathological changes in brain on male Wistar rats. The administration of MSG significantly increases serum level of fasting glucose, insulin, triglycerides, total cholesterol, low-density lipoprotein and decrease level of high-density lipoprotein. Significant low level of FRAP, GSH, SOD, CAT and higher level of MDA, PCO, AOPP, PMRS, NO, CRP, IL-6, TNF-α confirms substantial oxidative stress followed by inflammation after 100 mg MSG treatment. RT-PCR figure shows significant expression of neuroinflammatory gene IL-6 and TNF-α and histopathological examination revealed severe neurodegeneration in hippocampus (CA1 and CA3) and cerebral cortex region of brain at 100 mg MSG treatment. Our result provides evidence that MSG administration at 30 mg does not impose toxicity, however at 100 mg/kg body weight, which is considered a low dose, there is significant toxic effects and may be detrimental to health.

Innate immune responses to SARS-CoV-2.

This chapter provides an overview of the innate immune response to SARS-CoV-2, focusing on the recognition, activation, and evasion strategies employed by the virus. The innate immune system plays a crucial role in the early defense against viral infections, and understanding its response to SARS-CoV-2 is essential for developing effective therapeutic approaches. The chapter begins by explaining the basics of the innate immune system, including its components and salient features. It discusses the various pattern recognition receptors involved in recognizing SARS-CoV-2, such as toll-like receptors, RIG-I-like receptors, NOD-like receptors, and other cytosolic sensors. The binding and entry of the virus into host cells and subsequent activation of innate immune cells, including neutrophils, monocytes, macrophages, dendritic cells, NK cells, and ILCs, are explored. Furthermore, the secretion of key cytokines and chemokines, including type I interferons, IL-6, IL-17, and TNF-alpha, is discussed as part of the innate immune response. The concept of PANoptosis, involving programmed cell death mechanisms, is introduced as a significant aspect of the response to SARS-CoV-2. The chapter also addresses the innate immune evasion strategies employed by SARS-CoV-2, which allow the virus to evade or subvert the host immune response, contributing to viral persistence. Understanding these strategies is crucial for developing targeted therapies against the virus.

COVID-19 pathogenesis.

The pathogenesis of COVID-19 involves a complex interplay between host factors and the SARS-CoV-2 virus, leading to a multitude of clinical manifestations beyond the respiratory system. This chapter provides an overview of the risk factors, genetic predisposition, and multisystem manifestations of COVID-19, shedding light on the underlying mechanisms that contribute to extrapulmonary manifestations. The chapter discusses the direct invasion of SARS-CoV-2 into various organs as well as the indirect mechanisms such as dysregulation of the renin-angiotensin-aldosterone system (RAAS), immune response dysfunctions within the innate and adaptive immune systems, endothelial damage, and immunothrombosis. Furthermore, the multisystem manifestations of COVID-19 across different organ systems, including the cardiovascular, renal, gastrointestinal, hepatobiliary, nervous, endocrine and metabolic, ophthalmic, ear-nose-throat, reproductive, hematopoietic, and immune systems are discussed in detail. Each system exhibits unique manifestations that contribute to the complexity of the disease.

Varicella Zoster Associated Vasculopathy and Retinitis with Natalizumab Use in Multiple Sclerosis.

Natalizumab (Tysabri®, NTZ) is a monoclonal autoantibody approved for treatment of relapsing-remitting multiple sclerosis. NTZ inhibits leukocyte migration across the blood-brain barrier, preventing autoreactive cells from inciting an inflammatory immune response. This immunosuppression is highly efficacious in attenuating the risk of relapse of disease, but has been associated with opportunistic central nervous system (CNS) infections, most notably progressive multifocal leukoencephalopathy. Varicella-zoster and herpes simplex viruses have also been associated with NTZ, inciting a spectrum of disease, including encephalitis, meningitis, and acute retinal necrosis. While rare, these infections can result in devastating outcomes even when promptly identified and treated.   We present a case of combined CNS varicella zoster vasculitis and acute retinal necrosis in a 57-year-old woman maintained on monthly Natalizumab therapy, who presented with headache and visual field deficits.

Correlation of lymphocyte subsets and inflammatory biomarkers with disease severity in COVID-19 patients.

Objective: To determine the correlation of lymphocyte subsets and soluble serum inflammatory biomarkers with disease severity in coronavirus disease-2019 infection. METHODS: The retrospective study was conducted at the Department of Immunology, Sindh Institute of Urology and Transplantation (SIUI), Karachi, Pakistan from September 1 to November 30, 2021, and comprised data of patients admitted from June to July 2021 who tested positive for coronavirus disease-2019 on the basis of reverse transcription-polymerase chain reaction of nasopharyngeal swab specimens. The patients were categorised into severe group A and non-severe group B. Initial investigations included complete blood count, neutrophil-to-lymphocytes ratio, C-reactive protein, D-Dimers and serum ferritin levels. Lymphocyte subsets included cluster of differentiation-3+, cluster of differentiation-4+/ cluster of differentiation-3+, cluster of differentiation-8+ T lymphocytes, cluster of differentiation-19+B lymphocytes, cluster of differentiation-16+ cluster of differentiation-56+ Natural Killer cells and serum cytokine levels of interleukin-2, interleukin- 4, interleukin-6, interleukin-10, tumour necrosis factor-alpha and interferon gamma. They were correlated with disease severity. Data was analysed using SPSS 20. RESULTS: Of the 54 patients, 33(61.1%) were males and 21(38.9%) were females. There were 29(53.70%) patients in group A with median age 52 years (interquartile range: 43.5-65 years), and 25(46.29%) in group B with median age 50 years (interquartile range: 36.5-59 years) (p=0.241). Disease was significantly more severe in male patients compared to female (p=0.002). In group A, cluster of differentiation-3+ T cells were reduced in 21(72.4%) patients, cluster of differentiation-8+ T cells in 16(55.2%), cluster of differentiation-4+ T cells in 23(79.3%) and cluster of differentiation-19+ B cells in 8(27.6%). In group B, cluster of differentiation-3+ T cells were reduced in 10(40%) subjects, cluster of differentiation-8+ T cells in 7(28%), cluster of differentiation-4+ T cells in 12(48%) and cluster of differentiation-19+ B cells in 4(16%) patients. Serum cytokine levels were not significantly different between the groups (p>0.05). In group A, 7(24.13%) patients died, and in such cases, the neutrophil-to-lymphocytes ratio was significantly higher (p=0.037). Conclusion: Pro-inflammatory markers and cytokine levels increased, while lymphocyte subsets decreased with increasing severity of the disease.

Comparison of safety and efficacy of Netarsudil 0.02% and Bimatoprost 0.01% monotherapy and combination therapy in primary open-angle glaucoma and ocular hypertension.

PURPOSE: To study and compare the efficacy and safety profile of Rho-kinase inhibitor (netarsudil 0.02%) and prostaglandin analog (bimatoprost 0.01%) both as monotherapy and in combination. DESIGN: Prospective, randomized, monocentric, open-label clinical trial. METHODS: Patients ≥20 years of age with primary open-angle glaucoma or ocular hypertension (IOP >21 mmHg) were recruited and randomized to receive either netarsudil 0.02%, netarsudil 0.02% + bimatoprost 0.01%, or bimatoprost 0.01% once daily for a period of 12 weeks. IOP and side effects were documented at 4, 8, and 12 weeks. RESULTS: The mean treated IOP ranged 17.51-18.57 mmHg for netarsudil, 15.80-16.46 mmHg for bimatoprost, and 14.00-14.87 mmHg for the combination therapy group. The mean IOP reduction from baseline at 4, 8, and 12 weeks was found to be statistically significant ( P < 0.001) in all three groups. The safety profile of netarsudil/bimatoprost combination was consistent with each constituent individually. The only frequently observed ocular adverse event was conjunctival hyperemia, which was seen mostly in netarsudil and netarsudil + bimatoprost groups ( P < 0.001). CONCLUSION: The IOP-lowering effect of netarsudil 0.02% once daily is non-inferior to bimatoprost 0.01% in patients with POAG and ocular hypertension with acceptable ocular safety, and the combination therapy achieved a higher IOP-lowering effect. This group of medications can be a useful adjunct in patients on maximal therapy.