Steering the course of CAR T cell therapy with lipid nanoparticles.

Lipid nanoparticles (LNPs) have proven themselves as transformative actors in chimeric antigen receptor (CAR) T cell therapy, surpassing traditional methods and addressing challenges like immunogenicity, reduced toxicity, and improved safety. Promising preclinical results signal a shift toward safer and more effective CAR T cell treatments. Ongoing research aims to validate these findings in clinical trials, marking a new era guided by LNPs utility in CAR therapy. Herein, we explore the preference for LNPs over traditional methods, highlighting the versatility of LNPs and their effective delivery of nucleic acids. Additionally, we address key challenges in clinical considerations, heralding a new era in CAR T cell therapy.

Using Carbohydrate-Based Polymers to Facilitate Testicular Regeneration.

Male infertility is a significant global issue affecting 60-80 million people, with 40%-50% of cases linked to male issues. Exposure to radiation, drugs, sickness, the environment, and oxidative stress may result in testicular degeneration. Carbohydrate-based polymers (CBPs) restore testis differentiation and downregulate apoptosis genes. CBP has biodegradability, low cost, and wide availability, but is at risk of contamination and variations. CBP shows promise in wound healing, but more research is required before implementation in healthcare. Herein, we discuss the recent advances in engineering applications of CBP employed as scaffolds, drug delivery systems, immunomodulation, and stem cell therapy for testicular regeneration. Moreover, we emphasize the promising challenges warranted for future perspectives.

Functional role of autophagy in testicular and ovarian steroidogenesis.

Autophagy is an evolutionarily conserved cellular recycling process that maintains cellular homeostasis. Despite extensive research in endocrine contexts, the role of autophagy in ovarian and testicular steroidogenesis remains elusive. The significant role of autophagy in testosterone production suggests potential treatments for conditions like oligospermia and azoospermia. Further, influence of autophagy in folliculogenesis, ovulation, and luteal development emphasizes its importance for improved fertility and reproductive health. Thus, investigating autophagy in gonadal cells is clinically significant. Understanding these processes could transform treatments for endocrine disorders, enhancing reproductive health and longevity. Herein, we provide the functional role of autophagy in testicular and ovarian steroidogenesis to date, highlighting its modulation in testicular steroidogenesis and its impact on hormone synthesis, follicle development, and fertility therapies.

Multifaceted role of TRIM21 in inflammation.

Tripartite motif (TRIM) family members participate in a variety of cellular activities, such as intracellular signaling, development, cellular death, protein quality control, immunological defense, waste degradation, and the emergence of cancer. These proteins usually act as E3 ubiquitin ligase. The final line of resistance against infectious viruses is a cytosolic ubiquitin ligase and antibody receptor called TRIM containing 21. TRIM21, a protein with a tripartite structure, has been linked to autoimmune erythematosus, Sjogren's disorder, and innate immunity. TRIM21 may either promote the formation of specific cancer-activating proteins, resulting in their proteasomal degradation, or it may do neither, depending on the kind of cancer and cancer-causing trigger. The current research has shown that the antiviral action of TRIM mostly depends on their role as E3-ubiquitin ligases and a significant portion of the TRIM family mediates the transmission of innate immune cell signals and the subsequent production of cytokines. We highlighted the function of TRIM family members in various inflammatory diseases.

Emerging insights into the impacts of heavy metals exposure on health, reproductive and productive performance of livestock.

Heavy metals, common environmental pollutants with widespread distribution hazards and several health problems linked to them are distinguished from other toxic compounds by their bioaccumulation in living organisms. They pollute the food chain and threaten the health of animals. Biologically, heavy metals exhibit both beneficial and harmful effects. Certain essential heavy metals such as Co, Mn, Se, Zn, and Mg play crucial roles in vital physiological processes in trace amounts, while others like As, Pb, Hg, Cd, and Cu are widely recognized for their toxic properties. Regardless of their physiological functions, an excess intake of all heavy metals beyond the tolerance limit can lead to toxicity. Animals face exposure to heavy metals through contaminated feed and water, primarily as a result of anthropogenic environmental pollution. After ingestion heavy metals persist in the body for an extended duration and the nature of exposure dictates whether they induce acute or chronic, clinical or subclinical, or subtle toxicities. The toxic effects of metals lead to disruption of cellular homeostasis through the generation of free radicals that develop oxidative stress. In cases of acute heavy metal poisoning, characteristic clinical symptoms may arise, potentially culminating in the death of animals with corresponding necropsy findings. Chronic toxicities manifest as a decline in overall body condition scoring and a decrease in the production potential of animals. Elevated heavy metal levels in consumable animal products raise public health concerns. Timely diagnosis, targeted antidotes, and management strategies can significantly mitigate heavy metal impact on livestock health, productivity, and reproductive performance.

Extracellular Vesicles: the Next Frontier in Pregnancy Research.

Extracellular vehicles (EVs) have been involved in several aspects of pregnancy, including endometrial receptivity, embryo implantation, and embryo-maternal communication showing them associated with pregnancy disorders, such as preeclampsia, gestational diabetes mellitus, and preterm birth. Further research is warranted to fully comprehend the exact pathophysiological roles of EVs and to develop new therapies targeting EVs thereby improving pregnancy outcomes. Herein, we review the recent knowledge on the multifaceted roles of EVs during pregnancy and address the majority of the molecular interactions between EVs, maternal, and fetal cells with an emphasis on disorders of pregnancy under the influence of EVs. Moreover, we also discuss its applications in clinical trials followed by prospects.

Diagnostic and therapeutic value of EVs in lungs diseases and inflammation.

Extracellular vesicles (EVs) are membrane-derived messengers which have been playing an important role in the inflammation and pathogenesis of lung diseases. EVs contain varieties of DNA, RNA, and membrane receptors through which they work as a delivery system for bioactive molecules as well as intracellular communicators. EV signaling mediates tumor progression and metastasis. EVs are linked with many diseases and perform a diagnostic role in lung injury and inflammation so are used to diagnose the severity of diseases. EVs containing a variety of biomolecules communicate with the recipient cells during pathophysiological mechanisms thereby acquiring the attention of clinicians toward the diagnostic and therapeutic potential of EVs in different lung diseases. In this review, we summarize the role of EVs in inflammation with an emphasis on their potential as a novel candidate in the diagnostics and therapeutics of chronic obstructive pulmonary disease, asthma, and sarcoidosis.

Investigating the effect of different filaments and yarn structures on mechanical and physical properties of dual-core elastane composite yarns.

Dual-core yarns, containing two filaments within the core of the yarn, have gained increasing commercial and research interest recently, especially in denim manufacturing. The use of multi-components in dual-core yarns allows for tailoring the properties of the yarn and denim fabric. The type of filaments and fibers and their surface characteristics play a role in fiber-to-fiber cohesion within yarn structure. However, little has been reported regarding the effect of different filaments on the properties of dual-core yarns. The objective of this study was to investigate the effect of three different filaments, T400, polyester flat (PET flat) and polyester textured (PET textured) as well as two yarn structures, siro versus non-siro, on tensile, elastic and other properties of dual-core yarns at same twist level and linear density of the yarn. The results showed that the siro spun dual-core yarn containing T400 exhibited 25% higher tenacity compared with yarns containing other filaments. However, the plastic deformation of the yarn containing PET flat filament, having a higher initial modulus, was at a relatively lower level compared with T400 and PET textured. Overall, the siro yarn structure showed lower imperfections and higher tenacity compared with the non-siro yarn structure. The dual-core yarn containing T400 showed a higher level of moisture wicking compared with other filaments which can add to the comfort properties but a similar hairiness level. The findings of this study suggest that the use of a filament with a higher initial modulus can improve the stretch and recovery behavior of the dual-core yarns.

Mini-organs with big impact: Organoids in liver cancer studies.

Hepatocellular carcinoma, the most common primary liver cancer and a leading cause of death, is a difficult disease to treat due to its heterogeneous nature. Traditional models, such as 2D culture and patient-derived xenografts, have not proven effective. However, the development of 3D culture techniques, such as organoids, which can mimic the tumor microenvironment (TME) and preserve heterogeneity and pathophysiological properties of tumor cells, offers new opportunities for treatment and research. Organoids also have the potential for biomarker detection and personalized medication, as well as genome editing using CRISPR/Cas9 to study the behavior of certain genes and therapeutic interventions. This review explores to-the-date development of organoids with a focus on TME modeling in 3D organoid cultures. Further, it discusses gene editing using CRISPR/Cas9 in organoids, the challenges faced, and the prospects in the field of organoids.

Microplastics: unraveling the signaling pathways involved in reproductive health.

Microplastics (MPs) are biologically active environmental pollutants having significant impact on the ecosystem and human health. MPs have been reported to increase oxidative stress, resulting in tissue damage, developmental abnormalities, metabolic disorders, epigenetic changes, abnormal reproduction, and reduced gamete quality. At present, most of the existing literature has focused on the effects of MPs on the reproduction of various aquatic organisms; however, the effects of MPs on mammalian reproduction specifically humans are least studied except a few ones fragmentally discussing the effects of MPs on gametogenesis in human. This review discusses effects of MPs on male and female reproduction with a focus on different metabolic pathways involved in compromised gamete quality, gamete toxicity, apoptosis, and DNA damage.

Breaking down barriers: The potential of smarter CAR-engineered NK cells against solid tumors.

Natural killer (NK) cells are considered to be the foremost fighters of our innate immune system against foreign invaders and thus tend to promptly latch onto the virus-infected and tumor/cancerous cells, killing them through phagocytosis. At present, the application of genetically engineered Chimeric antigen receptor (CAR) receptors ensures a guaranteed optimistic response with NK cells and would not allow the affected cells to dodge or escape unchecked. Hence the specificity and uniqueness of CAR-NK cells over CAR-T therapy make them a better immunotherapeutic choice to reduce the load of trafficking of numerous tumor cells near the healthy cell populations in a more intact way than offered by CAR-T immunotherapy. Our review mainly focuses on the preclinical, clinical, and recent advances in clinical research trials and further strategies to achieve an augmented and efficient cure against solid tumors.

Plant growth-promoting bacterial consortia improved the physiology and growth of maize by regulating osmolytes and antioxidants balance under salt-affected field conditions.

This study was undertaken to see how microbial consortia influenced maize development and yield under salt-affected conditions. The efficacy of the pre-isolated bacterial strains Burkholderia phytofirmans, Bacillussubtilis, Enterobacter aerogenes, and Pseudomonas syringae and Pseudomonas fluorescens to decrease the detrimental effects of salt on maize was tested in four distinct combinations using Randomized Complete Block Design with three replicates. The results revealed that these strains were compatible and collaborated synergistically, with an 80% co-aggregation percentage under salt-affected conditions. Following that, these strains were tested for their ability to increase maize growth and yield under salt-affected field conditions. The photosynthetic rate (11-50%), relative water content (10-34%), and grain yield (13-21%) of maize were all increased by these various combinations. However, when Burkholderia phytofirmans, Enterobacter aerogenes and Pseudomonas fluorescens were combined, the greatest increase was seen above the un-inoculated control. Furthermore, as compared to the un-inoculated control, the same combination resulted in a 1.5-fold increase in catalase and a 2.0-fold increase in ascorbate concentration. These findings showed that a multi-strain consortium might boost maize's total yield response as a result of better growth under salt stress.

Self-assembled and Zn(II)-coordinated dipeptide nanoparticles with membrane-rupturing action on bacteria.

Metal ion-coordinated self-assembled short-chain amino acid peptide molecules with multi-photon excitation wavelengths and their photoluminescence properties are advantageous for fluorescence-based diagnostics and treatments of biological diseases based on their extra features of antibacterial agents. We have designed a novel strategy based on tryptophan molecule coordinated with Zn(II) ions in the form of biocompatible spherical nanoparticles of diameter 30-80 nm which have been used for antibacterial treatments against different kinds of pathogenic bacteria (Escherichia coli, Salmonella typhimurium, and Pseudomonas). Preferably, we have used tryptophan-phenylalanine (Trp-Phe), a dipeptide molecule having tryptophan as principal material against E. coli strains as antimicrobial agents for surface rupturing and killing purposes. Furthermore, based on single amino acid, tryptophan, self-assembled and Zn(II)-coordinated dipeptide nanoparticles (Zn-DPNPs) were studied against three types of multi-drug-resistant bacteria as an active antimicrobial agent. These antibacterial efficient nanoparticles may have best alternative of antibiotic drugs for clinical applications. The capability of self-assembled fluorescence behavior of Zn-coordinated dipeptide molecules and higher hydrophobicity against bacterial cell wall will perform as antimicrobial fluorescent agents. KEY POINTS: • Zn(II) and Cu(II) better coordinated into self-assembled NPs. • Fluorescence signals showed interaction of NPs with gram -ve cell wall. • Significant surface-damaging effects were observed in the case of Cu-DPNPs and Zn-DPNPs.

From barriers to novel strategies: smarter CAR T therapy hits hard to tumors.

Chimeric antigen receptor (CAR) T cell therapy for solid tumors shows promise, but several hurdles remain. Strategies to overcome barriers such as CAR T therapy-related toxicities (CTT), immunosuppression, and immune checkpoints through research and technology are needed to put the last nail to the coffin and offer hope for previously incurable malignancies. Herein we review current literature and infer novel strategies for the mitigation of CTT while impeding immune suppression, stromal barriers, tumor heterogeneity, on-target/off-tumor toxicities, and better transfection strategies with an emphasis on clinical research and prospects.

Recent advances to Neuroprotection: repurposing drugs against neuroinflammatory disorders.

Cell death is a natural mechanism for biological clearance for the maintenance of homeostasis in a dynamic microenvironment of the central nervous system. Stress and various factors can lead to imbalance between cellular genesis and cell death leading to dysfunctionality and a number of neuropathological disorders. Drug repurposing can help bypass development time and cost. A complete understanding of drug actions and neuroinflammatory pathways can lead to effective control of neurodegenerative disorders. This review covers recent advances in various neuroinflammatory pathways understanding, biomarkers, and drug repurposing for neuroprotection.

Unraveling the harmful effect of oxidative stress on male fertility: A mechanistic insight.

Male infertility is a widely debated issue that affects males globally. There are several mechanisms involved. Oxidative stress is accepted to be the main contributing factor, with sperm quality and quantity affected by the overproduction of free radicals. Excess reactive oxygen species (ROS) cannot be controlled by the antioxidant system and, thus, potentially impact male fertility and hamper sperm quality parameters. Mitochondria are the driving force of sperm motility; irregularities in their function may lead to apoptosis, alterations to signaling pathway function, and, ultimately, compromised fertility. Moreover, it has been observed that the prevalence of inflammation may arrest sperm function and the production of cytokines triggered by the overproduction of ROS. Further, oxidative stress interacts with seminal plasma proteomes that influence male fertility. Enhanced ROS production disturbs the cellular constituents, particularly DNA, and sperms are unable to impregnate the ovum. Here, we review the latest information to better understand the relationship between oxidative stress and male infertility, the role of mitochondria, the cellular response, inflammation and fertility, and the interaction of seminal plasma proteomes with oxidative stress, as well as highlight the influence of oxidative stress on hormones; collectively, all of these factors are assumed to be important for the regulation of male infertility. This article may help improve our understanding of male infertility and the strategies to prevent it.

Development and Characterization of Drug Loaded PVA/PCL Fibres for Wound Dressing Applications.

Nowadays, synthetic polymers are used in medical applications due to their special biodegradable, biocompatible, hydrophilic, and non-toxic properties. The materials, which can be used for wound dressing fabrication with controlled drug release profile, are the need of the time. The main aim of this study was to develop and characterize polyvinyl alcohol/polycaprolactone (PVA/PCL) fibres containing a model drug. A dope solution comprising PVA/PCL with the drug was extruded into a coagulation bath and became solidified. The developed PVA/PCL fibres were then rinsed and dried. These fibres were tested for Fourier transform infrared spectroscopy, linear density, topographic analysis, tensile properties, liquid absorption, swelling behaviour, degradation, antimicrobial activity, and drug release profile for improved and better healing of the wound. From the results, it was concluded that PVA/PCL fibres containing a model drug can be produced by using the wet spinning technique and have respectable tensile properties; adequate liquid absorption, swelling %, and degradation %; and good antimicrobial activity with the controlled drug release profile of the model drug for wound dressing applications.

Outcome of head injury in motorbike riders.

Objective: To determine the impact of helmet wearing on traumatic brain injury. Methods: We analyzed 400 cases of traumatic brain injury (TBI) in motorbike riders with and without helmet, from July 2017 to December 2020 presenting to the neurosurgery department at Jinnah Postgraduate Medical Center (JPMC), Karachi, Pakistan. The medical records were analyzed for CT scan findings, length of hospital stay, complications (mortality and disability), Glasgow Coma Scale (GCS) and Glasgow outcome score (GOS) at time of discharge. Result: A total of 400 patients with head injury due to motorbike accidents were included and all were male patients. They were equally divided into two groups, 200 in Group-A (with helmet) and 200 in Group-B (without helmet). Majority of the unhelmeted patients i.e. 102 (51%), needed admission in the Intensive Care Unit (ICU) compared to 70 (35%) in helmeted. When comparing non-helmeted patients to helmeted patients, the total median length of hospital stay was greater among non-helmeted patients (10 vs 05 days). Mortality was higher among non-helmeted patients seen in 50 (25%) as compared to 14 (7%) in helmeted patients. Overall, the good outcome was observed in 119 (59.5%) patients in Group-A as compared to70 (35%) patients in Group-B while 81 (40.5%) showed bad outcome in Group-A and 130 (64%) in Group-B. The failure to wear a helmet was found to be strongly linked with abnormal neuroimaging more complications, poor outcome and lower GCS on discharge as compared to patients using helmet. Conclusion: Lack of helmet use is linked to abnormal brain imaging, more complications, and a longer stay in the hospital after a head injury.

Gold nanocubes based optical detection of HIV-1 DNA via surface enhanced Raman spectroscopy.

Optical detection of HIV-1 DNA with surface enhanced Raman spectroscopy (SERS) is a quick and versatile method, having great potential in screening and characterization of HIV-1 virus particle. We have synthesized and applied novel gold nanocubes (AuNCs) for signal enhancement of SERS to study HIV-1 DNA strands by taking into account the specific vibrational bands of functional groups. Raman peaks at 562 cm-1, 800 cm-1, 1094 cm-1 were observed in both Human Random Control DNA and HIV-1 DNA, while three new peaks were detected in infected DNA at 421 cm-1, 1069 cm-1 and 1254 cm-1. Raman bands in case of AuNCs coated HIV-1 DNA molecules were observed with enhanced intensity values as compared to the silver nanoparticles-based SERS substrate. In case of silver nanoparticles (AgNPs) conjugate DNA, we get all signatures of HIV-1 virus at almost the same position with peak distortions, peak alterations and intensities reductions. We overall molecularly observed HIV-1 infected DNA and Human Random Control DNA, with high sensitivity and selectivity using highly sensitive and stable AuNCs in SERS. This technique can be utilized to identify molecular structures and chemical identification of biomacromolecules which can further be investigated as biomarkers for the screening of whole-body HIV-1 virus particles.

Multifaceted roles of extracellular RNAs in different diseases.

Extracellular RNAs (exRNAs) are novel circulating factors that can be used as biomarkers in various diseases. Their unique and diverse kinds, as well as their role as biomarkers, make them significant biomarkers. There has been immense work carried out since the discovery of exRNAs in circulation and other biological fluids to catalog and determine whether exRNAs may be utilized as indicators for health and illness. In this review, we aim to understand the current state of exRNAs in relation to various diseases and their potential as biomarkers. We will also review current issues and challenges faced in using exRNAs, with clinical and lab trials, that can be used as viable markers for different diseases.