Exploring the Impact of TLR-2 Signaling on miRNA Dysregulation in Intervertebral Disc Degeneration.

Toll-like receptors (TLRs) are key mediators of inflammation in intervertebral disc (IVD) degeneration. TLR-2 activation contributes to the degenerative process by increasing the expression of extracellular matrix-degrading enzymes, pro-inflammatory cytokines, and neurotrophins. As potent post-transcriptional regulators, microRNAs can modulate intracellular mechanisms, and their dysregulation is known to contribute to numerous pathologies. This study aims to investigate the impact of TLR-2 signaling on miRNA dysregulation in the context of IVD degeneration. Small-RNA sequencing of degenerated IVD cells shows the dysregulation of ten miRNAs following TLR-2 activation by PAM2CSK4. The miR-155-5p is most significantly upregulated in degenerated and non-degenerated annulus fibrosus and nucleus pulposus cells. Sequence-based target and pathway prediction shows the involvement of miR-155-5p in inflammation- and cell fate-related pathways and TLR-2-induced miR-155-5p expression leads to the downregulation of its target c-FOS. Furthermore, changes specific to the activation of TLR-2 through fragmented fibronectin are seen in miR-484 and miR-487. Lastly, miR-100-3p, miR-320b, and miR-181a-3p expression exhibit degeneration-dependent changes. These results show that TLR-2 signaling leads to the dysregulation of miRNAs in IVD cells as well as their possible downstream effects on inflammation and degeneration. The identified miRNAs provide important opportunities as potential therapeutic targets for IVD degeneration and low back pain.

The development of the Cognitive Assessment for Tagalog Speakers (CATS): A culturally and linguistically tailored test battery for Filipino Americans.

INTRODUCTION: Filipino Americans are one of the largest Asian American and Pacific Islander (AAPI) populations in the United States (US). Previous studies suggest that Filipino Americans have one of the highest incidence rates of Alzheimer's disease and related dementias (ADRD) among AAPI subgroups. Despite the expected increase in Filipino Americans with ADRD, no studies to-date have validated neuropsychological measures in the United States for speakers of Tagalog, a major language spoken by Filipino Americans. A significant barrier to dementia care and diagnosis is the lack of linguistically and socioculturally appropriate cognitive tasks for Tagalog speakers. To address this need, we developed and piloted the Cognitive Assessment for Tagalog Speakers (CATS), the first neuropsychological battery for the detection of ADRD in Filipino American Tagalog speakers. METHODS: Based on evidence-based neuropsychological batteries, we adapted and constructed de novo tasks to measure performance across 4 main cognitive domains: visual/verbal memory, visuospatial functioning, speech and language, and frontal/executive functioning. Tasks were developed with a team of bilingual English/Tagalog, bicultural Filipino American/Canadian experts, including a neurologist, speech-language pathologist, linguist, and neuropsychologist. We recruited Tagalog-speaking participants of age 50+ through social media advertisements and recruitment registries for this cross-sectional study. We present the CATS design and protocol. RESULTS: To-date, the CATS battery has been administered to 26 healthy control participants (age 64.5 ± 7.8 years, 18F/8 M) at an academic institution in Northern California, United States. The development and administration of the CATS battery demonstrated its feasibility but also highlighted the need to consider the effects of bilingualism, language typology, and cultural factors in result interpretation. DISCUSSION: The CATS battery provides a mechanism for cognitive assessment of Filipino Americans, a population that has been underrepresented in ADRD research. As we move toward the treatment and cure of ADRD, linguistically and socioculturally appropriate cognitive tests become even more important for equitable care.

Resveratrol Microencapsulation into Electrosprayed Polymeric Carriers for the Treatment of Chronic, Non-Healing Wounds.

Chronic, non-healing wounds represent a challenging socio-economic burden, demanding innovative approaches for successful wound management. Resveratrol (RSV) represents a promising therapeutic candidate, but its therapeutic efficacy and clinical applicability have been hampered by its rapid degradation and/or depletion. Herein, RSV was encapsulated into poly(ε-caprolactone) (PCL) microparticles by electrospraying with the aim to prolong and preserve RSV's release/activity, without affecting its therapeutic properties. Electrospraying led to the fabrication of spherical (2 to 10 µm in size), negatively charged (<−1 mV), and quasi-monodisperse (PDI < 0.3) microparticles, with 60% RSV release after 28 days. Microencapsulation of RSV into PCL prevented its photochemical degradation and preserved its antioxidant properties over 72 h. The RSV-PCL microparticles did not exhibit any cytotoxicity on human dermal fibroblasts. RSV released from the microparticles was biologically functional and induced a significant increase in collagen type I deposition. Furthermore, the produced RSV-PCL microparticles reduced the expression of inflammatory (IL-6, IL-8, COX-2) and proteolytic (MMP-2, MMP-9) mediators. Collectively, our data clearly illustrate the potential of electrosprayed polymeric carriers for the sustained delivery of RSV to treat chronic wounds.

Sulfated Hydrogels in Intervertebral Disc and Cartilage Research.

Hydrogels are commonly used for the 3D culture of musculoskeletal cells. Sulfated hydrogels, which have seen a growing interest over the past years, provide a microenvironment that help maintain the phenotype of chondrocytes and chondrocyte-like cells and can be used for sustained delivery of growth factors and other drugs. Sulfated hydrogels are hence valuable tools to improve cartilage and intervertebral disc tissue engineering. To further advance the utilization of these hydrogels, we identify and summarize the current knowledge about different sulfated hydrogels, highlight their beneficial effects in cartilage and disc research, and review the biofabrication processes most suitable to secure best quality assurance through deposition fidelity, repeatability, and attainment of biocompatible morphologies.