A floating 5-µm-diameter needle-electrode on the tissue for damage-reduced chronic neuronal recording in mice

Microelectrode technology is essential in electrophysiology and has made contributions to neuroscience as well as to medical applications. However, it is necessary to minimize tissue damage associated with needle-like electrode...

Treg: A Promising Immunotherapeutic Target in Oral Diseases

With the pandemic of COVID-19, maintenance of oral health has increasingly become the main challenge of global health. Various common oral diseases, such as periodontitis and oral cancer, are closely associated with immune disorders in the oral mucosa. Regulatory T cells (Treg) are essential for maintaining self-tolerance and immunosuppression. During the process of periodontitis and apical periodontitis, two typical chronic immune-inflammatory diseases, Treg contributes to maintain host immune homeostasis and minimize tissue damage. In contrast, in the development of oral precancerous lesions and oral cancer, Treg is expected to be depleted or down-regulated to enhance the anti-tumor immune response. Therefore, a deeper understanding of the distribution, function, and regulatory mechanisms of Treg cells may provide a prospect for the immunotherapy of oral diseases. In this review, we summarize the distribution and multiple roles of Treg in different oral diseases and discuss the possible mechanisms involved in Treg cell regulation, hope to provide a reference for future Treg-targeted immunotherapy in the treatment of oral diseases.

Type I Interferon-Mediated Regulation of Antiviral Capabilities of Neutrophils

Interferons (IFNs) are induced by viruses and are the main regulators of the host antiviral response. They balance tissue tolerance and immune resistance against viral challenges. Like all cells in the human body, neutrophils possess the receptors for IFNs and contribute to antiviral host defense. To combat viruses, neutrophils utilize various mechanisms, such as viral sensing, neutrophil extracellular trap formation, and antigen presentation. These mechanisms have also been linked to tissue damage during viral infection and inflammation. In this review, we presented evidence that a complex cross-regulatory talk between IFNs and neutrophils initiates appropriate antiviral immune responses and regulates them to minimize tissue damage. We also explored recent exciting research elucidating the interactions between IFNs, neutrophils, and severe acute respiratory syndrome-coronavirus-2, as an example of neutrophil and IFN cross-regulatory talk. Dissecting the IFN-neutrophil paradigm is needed for well-balanced antiviral therapeutics and development of novel treatments against many major epidemic or pandemic viral infections, including the ongoing pandemic of the coronavirus disease that emerged in 2019.

Three-micrometer-diameter needle electrode with an amplifier for extracellular in vivo recordings

Microscale needle-electrode devices offer neuronal signal recording capability in brain tissue; however, using needles of smaller geometry to minimize tissue damage causes degradation of electrical properties, including high electrical impedance and low signal-to-noise ratio (SNR) recording. We overcome these limitations using a device assembly technique that uses a single needle-topped amplifier package, called STACK, within a device of ∼1 × 1 mm2. Based on silicon (Si) growth technology, a <3-µm-tip-diameter, 400-µm-length needle electrode was fabricated on a Si block as the module. The high electrical impedance characteristics of the needle electrode were improved by stacking it on the other module of the amplifier. The STACK device exhibited a voltage gain of >0.98 (−0.175 dB), enabling recording of the local field potential and action potentials from the mouse brain in vivo with an improved SNR of 6.2. Additionally, the device allowed us to use a Bluetooth module to demonstrate wireless recording of these neuronal signals; the chronic experiment was also conducted using STACK-implanted mice.

The Effect of Dandang Gendis Extract (Clinacanthus nutans) on Kidney Histopathological Features of Diabetic Rats Model

Changes in kidney homeostasis due to diabetes can cause oxidative stress which then caused tissue damage that leads to diabetic nephropathy. Clinacanthus nutans extract is known to contain antioxidants that are reported to play an important role in the body’s defense system against oxidative stress to minimize tissue damage. This study aims to know the effect of Clinacanthus nutans leaf extract administration on kidney histopathological features of the diabetic rats model. A total of 35 rats were induced by streptozotocin which then divided into 5 groups and given Clinacanthus nutans extract with a dose of 75 mg/kgBW, 150 mg/kgBW and 300 mg/kgBW then compare with CMC-Na as control and metformin as standard drug for 14 days. The kidney histopathology was evaluated under a light microscope against the damage criteria that occurred in the proximal tubules of the kidney. As the result the least amout of kidney damage was on treatment group at dose 300 mg/kgBW, followed by extract with dose 75 mg/kgBW, 150 mg/kgBW, and metformin. In conclusion Clinacanthus nutans extract with a dose of 75 mg/kgBW, 150 mg/kgBW, and 300 mg/kgBW can improve the kidney histopathological feature of the diabetic rats model. Keywords: diabetes mellitus; histopathology; diabetic nephropathy; Clinacanthus nutans

Plants as Sources of Anti-Inflammatory Agents

Plants represent the main source of molecules for the development of new drugs, which intensifies the interest of transnational industries in searching for substances obtained from plant sources, especially since the vast majority of species have not yet been studied chemically or biologically, particularly concerning anti-inflammatory action. Anti-inflammatory drugs can interfere in the pathophysiological process of inflammation, to minimize tissue damage and provide greater comfort to the patient. Therefore, it is important to note that due to the existence of a large number of species available for research, the successful development of new naturally occurring anti-inflammatory drugs depends mainly on a multidisciplinary effort to find new molecules. Although many review articles have been published in this regard, the majority presented the subject from a limited regional perspective. Thus, the current article presents highlights from the published literature on plants as sources of anti-inflammatory agents.

Sputtered porous Pt for wafer-scale manufacture of low-impedance flexible microelectrodes

Recording electrical activity from individual cells in vivo is a key technology for basic neuroscience and has growing clinical applications. To maximize the number of independent recording channels as well as the longevity, and quality of these recordings, researchers often turn to small and flexible electrodes that minimize tissue damage and can isolate signals from individual neurons. One challenge when creating these small electrodes, however, is to maintain a low interfacial impedance by applying a surface coating that is stable in tissue and does not significantly complicate the fabrication process. Here we use a high-pressure Pt sputtering process to create low-impedance electrodes at the wafer scale using standard microfabrication equipment. Direct-sputtered Pt provides a reliable and well-controlled porous coating that reduces the electrode impedance by 5-9 fold compared to flat Pt and is compatible with the microfabrication technologies used to create flexible electrodes. These porous Pt electrodes show reduced thermal noise that matches theoretical predictions. In addition, we show that these electrodes can be implanted into rat cortex, record single unit activity, and be removed all without disrupting the integrity of the coating. We also demonstrate that the shape of the electrode (in addition to the surface area) has a significant effect on the electrode impedance when the feature sizes are on the order of tens of microns. Overall, porous Pt represents a promising method for manufacturing low-impedance electrodes that can be seamlessly integrated into existing processes for producing flexible neural probes.

An actuated neural probe architecture for reducing gliosis-induced recording degradation

Glial encapsulation of chronically implanted neural probes inhibits recording and stimulation, and this signal loss is a significant factor limiting the clinical viability of most neural implant topologies for decades-long implantation. We demonstrate a mechanical proof of concept for silicon shank-style neural probes intended to minimize gliosis near the recording sites. Compliant whiskers on the edges of the probe fold inward to minimize tissue damage during insertion. Once implanted to the target depth and retracted slightly, these whiskers splay outward. The splayed tips, on which recording sites could be patterned, extend beyond the typical 50-100 micron radius of a glial scar. The whiskers are micron-scale to minimize or avoid glial scarring. Electrically inactive devices with whiskers of varying widths and curvature were designed and monolithically fabricated from a five-micron silicon-on-insulator (SOI) wafer, and their mechanical functionality was demonstrated in a 0.6% agar brain phantom. Deflection was plotted versus deflection speed, and those that were most compliant actuated successfully. This probe requires no preparation for use beyond what is typical for a shank-style silicon probe.

Recent Advances in the Molecular Mechanisms Underlying Pyroptosis in Sepsis

Sepsis is recognized as a life-threatening organ dysfunctional disease that is caused by dysregulated host responses to infection. Up to now, sepsis still remains a dominant cause of multiple organ dysfunction syndrome (MODS) and death among severe condition patients. Pyroptosis, originally named after the Greek words “pyro” and “ptosis” in 2001, has been defined as a specific programmed cell death characterized by release of inflammatory cytokines. During sepsis, pyroptosis is required for defense against bacterial infection because appropriate pyroptosis can minimize tissue damage. Even so, pyroptosis when overactivated can result in septic shock, MODS, or increased risk of secondary infection. Proteolytic cleavage of gasdermin D (GSDMD) by caspase-1, caspase-4, caspase-5, and caspase-11 is an essential step for the execution of pyroptosis in activated innate immune cells and endothelial cells stimulated by cytosolic lipopolysaccharide (LPS). Cleaved GSDMD also triggers NACHT, LRR, and PYD domain-containing protein (NLRP) 3-mediated activation of caspase-1 via an intrinsic pathway, while the precise mechanism underlying GSDMD-induced NLRP 3 activation remains unclear. Hence, this study provides an overview of the recent advances in the molecular mechanisms underlying pyroptosis in sepsis.