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Biology subjects

Azizi, M.

Publications and source records attributed to Azizi, M..

6 recordsLinked to original sources

Protective Effects of Boric Acid Against LPS-Induced Inflammation and Apoptosis in a Primary Human Chondrocyte Model of Osteoarthritis

Osteoarthritis is characterized by inflammation, chondrocyte dysfunction, and progressive cartilage degradation. Boric acid (BA), a physiologically relevant boron compound, has shown anti-inflammatory properties, but its effects on human articular chondrocytes remain unclear. This study investigated whether BA could protect primary human chondrocytes against lipopolysaccharide-induced inflammatory injury. Cell survival, membrane damage, apoptosis, inflammatory mediator production, and expression of genes related to inflammation and extracellular matrix degradation were assessed. BA improved chondrocyte survival and reduced membrane damage and apoptosis following inflammatory stimulation. It also suppressed inflammatory and matrix-degrading gene expression, nitrite production, and the release of proinflammatory mediators. These protective effects were generally more pronounced with the higher treatment dose. Analysis of publicly available human chondrocyte RNA-sequencing datasets provided complementary support for the relevance of several investigated inflammatory and catabolic targets. Overall, these findings demonstrate that BA protects primary human chondrocytes against inflammatory and catabolic injury and support its further investigation as a potential chondroprotective approach in osteoarthritis.

pharmacology and toxicology↗

DNA-Based Nanoprobes for Fluorescence K+ Sensing in Neural Systems

SignificanceAbnormalities in potassium ion concentrations across subregions of the hippocampus have been implicated in seizures and other pathologies. Direct measurements of potassium ion concentrations are largely made using invasive electrodes, which do not allow for wide spatial coverage. This fluorescent nanoparticle potassium sensor enables direct visualization of potassium dynamics and represents a minimally invasive alternative to electrode-based methods. AimHere, we present a DNA-based fluorescence nanoprobe capable of sensing relative concentrations of potassium ions within populations of neurons. We present its effectiveness in monitoring neuronal K+ dynamics in response to electrical stimulation ex vivo. ApproachWe used widefield fluorescence microscopy to monitor changes in fluorescence intensity in labeled brain tissue in response to electrical stimulation ex vivo. ResultsWe found that our nanoprobe could be retained within the intracellular compartment and modulate in fluorescence intensity linearly in response to induced electrical current. Our K+ Sensor showed a fractional fluorescence change of approximately 1% per 10 mA of applied stimulation current in brain tissue. Optical spectroscopy confirmed the selectivity of the nanoprobes to potassium ions over other endogenous ions. ConclusionsOur findings indicate that this nanoprobe can be used to detect more complex potassium dynamics implicated in various pathologies of the nervous system, such as migraines, seizures, and trauma.

bioengineering↗

Linking in vivo muscle dynamics to in situ force-length and force-velocity reveals that guinea fowl lateral gastrocnemius operates at shorter than optimal lengths

Force-length (F-L) and force-velocity (F-V) properties characterize skeletal muscles intrinsic properties under controlled conditions, and it is thought that these properties can inform and predict in vivo muscle function. Here, we map dynamic in vivo operating range and mechanical function during walking and running, to the measured in situ F-L and F-V characteristics of guinea fowl (Numida meleagris) lateral gastrocnemius (LG), a primary ankle extensor. We use in vivo patterns of muscle tendon force, fascicle length, and activation to test the hypothesis that muscle fascicles operate at optimal lengths and velocities to maximize force or power production during walking and running. Our findings only partly support our hypothesis: in vivo LG velocities are consistent with optimizing power during work production, and economy of force at higher loads. However, LG does not operate at lengths on the force plateau ({+/-}5% Fmax) during force production. LG length was near L0 at the time of EMG onset but shortened rapidly such that force development during stance occurred almost entirely on the ascending limb of the F-L curve, at shorter than optimal lengths. These data suggest that muscle fascicles shorten across optimal lengths in late swing, to optimize the potential for rapid force development near the swing-stance transition. This may provide resistance against unexpected perturbations that require rapid force development at foot contact. We also found evidence of passive force rise (in absence of EMG activity) in late swing, at lengths where passive force is zero in situ, suggesting that dynamic history dependent and viscoelastic effects may contribute to in vivo force development. Direct comparison of in vivo work loops and physiological operating ranges to traditional measures of F-L and F-V properties suggests the need for new approaches to characterize dynamic muscle properties in controlled conditions that more closely resemble in vivo dynamics.

physiology↗

Ladder shaped microfluidic system enabling rapid antibiotic susceptibility testing with standardized concentration panel

Antibiotics are often prescribed before pathogens are identified and susceptibility to the prescribed drug is confirmed; laboratory results may take up to 3 days. Using rapid antibiotic susceptibility testing (AST) this timeline can be compressed. We designed a microfluidic ladder-based system that generates a twofold serial dilution of antibiotics comparable to current national and international standards. This consolidated design, with minimal handling steps, has cut down the time-to-result for AST from 16-20 h to 4-5 h. Our system has a 91.75 % rate of agreement with the commercial AST system for Gram-negative and Gram-positive bacterial isolates from canine urinary tract infections (UTI) tested against seven clinically relevant antibiotics. Overall, the system showed a matching rate of 92.71 % - 94.54 % with Gram-negative pathogens, and 85.00 % - 88.57 % with Gram-positive pathogens with no statistical difference between the pathogens or antibiotics. We also tested bacteria filtered directly from urine samples, potentially reducing the total sample-to-result time from 2-3 days to 4 hours.

microbiology↗

mRNA-based vaccine candidate COReNAPCIN(R) induces robust humoral and cellular immunity in mice and non-human primates

At the forefront of biopharmaceutical industry, the messenger RNA (mRNA) technology offers a flexible and scalable platform to address the urgent need for world-wide immunization in pandemic situations. This strategic powerful platform has recently been used to immunize millions of people proving both of safety and highest level of clinical efficacy against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we provide preclinical report of COReNAPCIN(R); a vaccine candidate against SARS-CoV-2 infection. COReNAPCIN(R) is a nucleoside modified mRNA-based vaccine formulated in lipid nanoparticles (LNPs) for encoding the full-length prefusion stabilized SARS-CoV-2 spike glycoprotein on the cell surface. Vaccination of C57BL/6 and BALB/c mice and rhesus macaque with COReNAPCIN(R) induced strong humoral responses with high titers of virus-binding and neutralizing antibodies. Upon vaccination, a robust SARS-CoV-2 specific cellular immunity was also observed in both mice and non-human primate models. Additionally, vaccination protected rhesus macaques from symptomatic SARS-CoV-2 infection and pathological damage to the lung upon challenging the animals with high viral loads of up to 2x108 live viral particles. Overall, our data provide supporting evidence for COReNAPCIN(R) as a potent vaccine candidate against SARS-CoV-2 infection for clinical studies.

immunology↗

Progressive Sperm Separation Using Parallelized, High-Throughput, Microchamber-based Microfluidics

Motility is one of the most important factors in sperm migration toward egg. Therefore, sperm separation based on motility increases the chance of the best sperm selection in the process of infertility treatments. Unfortunately, it is now vastly done by conventional procedures which lack certain delicacy and precision and increase the risk of damage to sperm cells. Microfluidic systems, on the other hand, can sort sperm in a less intrusive way. However, microfluidic techniques have yet to receive widespread adoption in clinical settings, not only due to their relatively cumbersome operation, but also their extremely low outcome, leaving them inefficient in practice. Here we propose a microchamber-based microfluidic platform that can separate progressive motile sperm from nonviable sperm and debris as well as trapped nonprogressive sperm in the microchambers. Our platform is operated in a short period of time (<10 min) with an excellent degree of controllability, without any prior sample preparation. Our results show that the microchambers depth does not affect the residence time of motile sperm. Therefore, we are able to inspect high sample volumes (1 mL) within the same time. Furthermore, we maximize the concentration of the collected sperm by tuning the washing medium flow rate above the sperm rheotactic threshold. We foresee that our microfluidic platform may provide a facile solution for high-throughput, robust, and easy-to-modify for collection of progressive sperm needed for assisted reproductive technologies (ARTs). Significance StatementAssisted Reproductive Technologies require efficient, minimally invasive, and fast methods of sperm separation. Centrifugation methods used in clinics and biological research labs, fall short in these aspects as they are low-yield, intrusive to sperms DNA, and time consuming. We have developed a microchamber-based microfluidic platform for high-throughput separation of progressive motile sperm from undiluted raw semen samples. The method was further optimized to increase the concentration of collected samples. Higher concentration of collected samples combined with higher motility of the separated sperm compared to those in raw semen, make it a suitable choice in clinical applications, fertility diagnostics, and fundamental research.

bioengineering↗