Abstract:

Despite significant advancements, prosthetic hernia repair continues to face unacceptably high complication rates, including postoperative discomfort and chronic pain. These issues often stem from poor biological responses, such as the formation of stiff scar tissue and mesh shrinkage, commonly associated with traditional static meshes and plugs. Recent studies have challenged the conventional approach of reinforcing the groin through fibrotic incorporation of meshes, particularly in light of new evidence on the degenerative origins of many types of abdominal hernias such as groin hernias. In response, the Stenting & Shielding (S&S) Hernia System, a newly designed 3D dynamic device, has been developed for dissection free laparoscopic placement to permanently obliterate hernia defects. Unlike conventional meshes, this device induces a probiotic biological response, promoting viable tissue growth rather than fibrotic plaque formation. In a porcine experimental model, the S&S device demonstrated the development of a great amount of muscle fibers, alongside nervous and vascular structures, within well-perfused connective tissue. Histological analysis of biopsy specimen excised from the experimental animals revealed progressive muscle fiber maturation from early myocyte development in the short term to fully developed muscle bundles in the long term. The enhanced biological response observed with the S&S device suggests a promising shift in hernia repair, potentially reversing the degenerative processes of hernia formation and promoting tissue regeneration. The S&S Hernia System described here can be classified not merely as a conventional hernia implant, but as part of a new category of hernia devices: the dynamic regenerative scaffold.

Abstract: This file describes a model called the SEQIRP model [8] which is a modified SIR model and it has been proposed by Dr Pabel Shahrear, S. M. Saydur Rahman, Md Mahadi Hasan Nahid from Shahjalal University of Science and Technology, Bangladesh which uses some basic parameters of Covid – 19 to predict the future of Covid 19 situation. We have used the data from 01 December 2021 to January 05, 2022, to predict the next peak point of COVID-19 in the next 250 days from December 01, 2021. Here we calculated the Basic Reproduction Number R0 by using Next-generation matrix, and to state the result from the model, we have used MATLAB to simulate our analysis by using the fourth-order Runge-Kutta (RK4) method and validate the results using fourth-order polynomial regression. Finally, we have got our prediction for Covid – 19. After getting the result we have taken the data from April 1, 2021, to February 28, 2022, and do a statistical analysis by using descriptive statistics and a histogram by using Microsoft Excel, which will validate the accuracy of our model. We have analyzed the SEQIRP model [8] with newly available data and tried to predict the next wave of COVID-19 in Bangladesh, and then we tried to validate the result with statistical analysis to achieve the model’s accuracy. Finally, we can claim the usefulness of the model in Bangladesh that, in the future, should we use the model to determine the wave of COVID-19 or not. This result of our model represents the effect of Covid 19 in Bangladesh.

Abstract: Enormous progress has been made towards understanding the pathophysiology of Alzheimer’s disease (AD) over the recent years through the advancement of research in the field of AD research. However, the unavailability of an appropriate drug for treatment raises several questions and scores the lake of thorough understanding the regulatory mechanisms underlying the disease pathophysiology and thereby the needs of further research for deeper understanding and uncover the hidden complexity. Most of the drugs that have been designed and proceed to clinical trials are focused on clearing of the aggregates of amyloid beta and the neurofibrillary tangles that are made of phosphorylated, while the focus on neuroinflammatory pathways is also emerging. Other pathological pathways that have profound regulatory roles underlying AD dementia include APOE mediated cholesterol transportation and metabolism, TREM2 mutation, DNA methylation, histone modification and non-coding RNAs etc. This review is particularly focus on how APOE, TREM2, DNA methylation, histone modification and non-coding RNAs contribute to neuroinflammation and leads to dementia of AD.

Abstract: Vascular smooth muscle cells (VSMCs) can dynamically change their phenotype between con-tractile and synthetic forms in response to environmental stress, which is pivotal in maintaining vascular homeostasis and mediating pathological remodeling of blood vessels. We previously reported that suppression of canonical transient receptor potential 6 (TRPC6) activation by Ca2+ entry sustains VSMCs contractile phenotype and promotes the blood flow recovery after hindlimb ischemia. In contrast, a metal biomolecule, Zn2+ mobilized by TRPC6 channel activation, is revealed to exert a potential beneficial effect on cardiac contractility. However, the role of TRPC6-mediated Zn²⁺ influx in VSMCs phenotypic switching is still unknown. Here we found the involvement of Zn²⁺ influx through TRPC6 channels in TGFβ-induced contractile differentiation of rat aorta-origin smooth muscle cells (RAoSMCs). Using wild type (WT)- and Zn2+ permeation-dead TRPC6 (KYD) mutant-expressing RAoSMCs, we revealed that pharmacological TRPC6 activation by PPZ2 enhanced the intracellular Zn2+ amounts which overcame TGFβ-induced intracellular Zn2+ depletion and contractile differentiation in RAoSMCs (WT), but failed in RAoSMCs (KYD). There is no significant difference in TRPC6 currents of both RAoSMCs (WT) and (KYD) cells with or without TGFβ stimulation. In addition, PPZ2 attenuated the progression of vascular remodeling caused by chronic angiotensin II treatment in mice. These data suggest that Zn2+ influx through TRPC6 channels will be a therapeutic potential for vascular diseases characterized by maladaptive phenotypic switching.

Abstract:

The theories of Evolution and Big Bang have brought a major impact upon the scientific and societal perception upon the origins, abilities and roles of mankind on Earth. It is conclusively evident that Mother Nature and the physical realm is autonomous and all phenomena in the world occur without an imposition against the “free will” of such events and patterns. Nevertheless, this extent of freedom does not imply that life on Earth represents an accident and has no purpose. By careful analysis of ancient religious texts, it can be suggested even otherwise, that it is especially free will that is offered as a gift from outside of the physical dimensions of existence, with the purpose of a continuous edification and improvement of the overall life conditions and of the human perception. It may be that the multi-generational focus on improvement and progress have been misattributed as a long-term evolution of species, that humans came from animal ancestors and that there is a blurred line associating humans with animals. Furthermore, it may be that scientists based their suggestions that no outside Creator would have brought the Earth into existence on physical perspectives, when the extra-dimensional process of Creation implies that all elements of the physical existence undergo a process of Creation from the outside, where time, space and physical matter do not exist, in spite of such elements possibly reflecting unseen elements of the meta-physical world. Finally, there is the following example that deserves attention within the scientific community; just because all living cells - human, animal and plant - contain DNA chromosomes, ribosomes, mitochondria and a plasma membrane, it does not indicate that humans are animals, just as this does not indicate that plants are animals. In Science, there is a golden statement, that correlation does not imply causation. This example is in complete agreement with the verses of the Book of Genesis in the Holy Scriptures regarding the origins of life; namely, that animals could have been created by an Author of all life on Earth so that man would experience companionship. Another major accordance with the teachings of the Holy Scriptures is the fact that life emerged from the water, and not from the soil, although the soil constituted the second principal means of the commencement and extension of life. Namely, after life first emerged in the seas and the oceans from bacteria, a few bacteria were passed from the marine water into the nearby soil on islands and surrounding land through the circulatory air above the sea level. Afterward, the first life forms emerged from the soil, via the transferred bacteria. Eastern Orthodox Christianity regards water as the principal environment of both physical and spiritual birth. Overall, an improved scientific perception of the timeline of life on Earth may be reached via an approach that combines molecular biology with quantum physics, given that the three layers of Science - Biology, Chemistry and Physics - together with their foundational layer of Mathematics, are in fact situated in a relationship of complete harmony.

Abstract: Sall4 as a pivotal transcription factor has been extensively studied across diverse bio-logical processes, including stem cell biology, embryonic development, hematopoiesis, tissue stem/progenitor maintenance, and the progression of various cancers. Recent re-search highlights Sall4's emerging roles in modulating cardiac progenitors and cellular reprogramming, linking its functions to early heart development and regenerative med-icine. These findings provide new insights into the critical functions of Sall4 in cardio-biology. This review explores Sall4's complex molecular mechanisms and their implications for advancing cardiac regenerative medicine.

Abstract: Human Parvovirus B19 (B19V) is a widespread virus, causing erythema infectiosum in children and several clinical manifestations from acute to persistent infections in adults. In early 2024, ECDC reported an increased human parvovirus B19 circulation in 14 European countries. A Parvovirus B19 outbreak was also reported in Tuscany, Italy, prompting a detailed investigation of its genetic characteristics. This study is the first Italian report on this outbreak, which carries out a phylogenetic analysis based on the complete coding B19V genomes of 23 positive samples. Phylogenetic clustering assigned all isolates to the G1a genotype, although with some mutations in NS1, VP1 and VP2, compared to the Reference strains.

Abstract: Compartment boundaries divide the embryo into segments with distinct fates and functions. In the vascular system, compartment boundaries organize endothelial cells into arteries, capillaries, and veins that are the fundamental units of a circulatory network. For vascular smooth muscle cells (SMCs) such boundaries produce mosaic patterns of investment based on embryonic origins with important implications for the non-uniform distribution of vascular disease later in life. Morphogenesis of blood vessels requires vascular cell movements within compartments as highly-sensitive responses to changes in fluid flow shear stress and wall strain. These movements underlie remodeling of primitive plexuses, expansion of lumen diameters, regression of unused vessels, and building multilayered artery walls. Although loss of endothelial compartment boundaries can produce arterial-venous malformations, little is known about the consequences of mislocalization or failure to form SMC origin-specific boundaries during vascular development. We propose that the failure to establish a normal compartment boundary between cardiac neural crest-derived SMCs of the 6th pharyngeal arch artery (future ductus arteriosus) and paraxial mesoderm-derived SMCs of the dorsal aorta in mid-gestation embryos leads to aortic coarctation observed at birth. This model raises new questions about the effects of fluid flow dynamics on SMC investment and the formation of SMC compartment borders during pharyngeal arch artery remodeling and vascular development.

Abstract:

Understanding ecological integrity of protect area is a central topic for the construction and conservation of these key areas. An ecological integrity framework based on landscape ecology was developed in this research, which include a series of index to monitor and evaluate the status and conditions of the landscape among different functional zone in the Xiangjiangyuan Provincial Nature Reserve (XPNR). The result showed that the XPNR has higher ecological quality, and less anthropogenic influence, the ecosystem of the XPNR was generally well maintained. The important landscape types of the XPNR include evergreen broad-leaved forest (EBLF), mixed evergreen deciduous broad-leaved forest (MEDBLF), deciduous broad-leaved forest (DBLF), etc., which have high authenticity and high conservation value. As the result of evaluation of landscape fragmentation and human interference in the three functional zones showed that the core zone < the buffer zone < the experimental zone, which was good to fit the conservation and management requirements of the XPNR. The landscape fragmentation analysis for the important landscape types in all functional area showed that the experimental area and the buffer area were relatively more severe, the core area was lighter with minimal anthropogenic impacts and the most complete protection. As the sustainability and management goal, we suggested some more effectively policies to continuously improve the ecosystem integrity.

Abstract:

This study investigated the pharmacokinetics of levofloxacin niosomes following a single dose administered intraperitoneally to Sprague Dawley rats, using conventional unentrapped drug as reference. Guided by results of previous studies, an experimental design software (DoE Fusion One) was used to design screening experiments that provided factor combinations and processing variable settings that resulted in an optimized formulation. Optimized niosomes of levofloxacin were prepared, characterized and evaluated in vitro for drug release rate. The well-characterized formulation was used for in vivo study in Sprague Dawley rats in a non-cross over parallel study. One of two groups of rats (n = 6 each) was injected intraperitoneally with conventional levofloxacin and the other with levofloxacin niosomes at 7.5mg/kg/dose. Blood samples were collected at ½, 1, 2, 4, 8, 12, 18, 24, 48 and 72 hours via tail snip. Drug concentrations were determined using a validated high-performance liquid chromatographic (HPLC) method. The plasma concentration versus time data from rats were fed into the Gastroplus software (Simulations Plus, CA) and used to model the pharmacokinetic profiles of the i.p. levofloxacin and its niosomes. The optimized drug-loaded niosomes used for in vivo rat study had a mean size of 368.8 (± 11.0 SE), encapsulation efficiency (EE) of 34.21 %, Zeta potential of -42.10 (± 2.07 SE) and mean polydispersity index (PDI) of 0.316 (± 0.014 SE). Following i.p. injection, levofloxacin release was controlled with less than 80 % released in 6 h and about 90% released in 12 h. Modeling of levofloxacin bio-disposition following i.p. injection in rats with Akaike information criterion (AIC) and Schwarz criterion (SC) indicated that the niosomes formulations are best fitted to one-compartment model while the conventional drug formulation followed two-compartment model. The niosomal formulation appeared to alter the biodistribution of levofloxacin, and concentrated the drug in the vascular compartment with slow, sustained distribution outside of the vascular compartment. Overall, the niosomes formulation showed significant increase in levofloxacin mean residence time (MRT), prolonged its elimination half-life (t1/2) and decrease its volume of distribution (Vd). Encapsulation of levofloxacin in niosomes altered its pharmacokinetic profile. It appears that, by vesicular encapsulation, niosomes altered levofloxacin biodistribution possibly by preventing its binding to plasma protein while correspondingly increasing its residence time in systemic circulation. Thus, by protecting intraperitoneally injected levofloxacin en route into the plasma, niosomes significantly enhance its delivery to, and concentration in, the intravascular compartment with enanced potential for treating intravascular conditions like bacteremia.