Development of a porous layer-by-layer microsphere with branched aliphatic hydrocarbon porogens

Porous polymer microspheres are employed in biotherapeutics, tissue engineering, and regenerative medicine. Porosity dictates cargo carriage and release that are aligned with the polymer physicochemical properties. These include material tuning, biodegradation, and cargo encapsulation. How uniformity of pore size affects therapeutic delivery remains an area of active investigation. Herein, we characterize six branched aliphatic hydrocarbon-based porogen(s) produced to create pores in single and multilayered microspheres. The porogens are composed of biocompatible polycaprolactone, poly(lactic-co-glycolic acid), and polylactic acid polymers within porous multilayered microspheres. These serve as controlled effective drug and vaccine delivery platforms

Europium-doped cerium oxide nanoparticles for microglial Aβ clearance and homeostasis

Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Pathologically, it is characterized by the deposition of amyloid beta (Aβ) plaques and presence of neurofibrillary tangles. These drive microglia neuroinflammation and consequent neurodegeneration. While the means to affect Aβ plaque accumulation was achieved how it affects disease outcomes remains uncertain. Cerium oxide (CeO2) reduces Aβ plaques, oxidative stress, inflammation, and Alzheimer’s disease (AD) signs and symptoms. Specifically, CeO2 nanoparticles (CeO2NPs) induces free radical scavenging and cell protective intracellular signaling. This can ameliorate the pathobiology of an AD-affected brain. In order to investigate, CeO2NPs affects for microglia neurotoxic responses a novel formulation of europium doped CeO2NPs (EuCeO2NPs) was synthesized. We then tested EuCeO2NPs for its’ abilities to generate cellular immune homeostasis in AD models. EuCeO2NPs attenuated microglia BV2 inflammatory activities after Aβ1–42 exposure by increasing the cells’ phagocytic and Aβ degradation activities. These were associated with increases in the expression of the CD36 scavenger receptor. EuCeO2NPs facilitated Aβ endolysosomal trafficking and abrogated microglial inflammatory responses. We posit that EuCeO2NPs may be developed as an AD immunomodulator

Multipolymer microsphere delivery of SARS-CoV-2 antigens

Effective antigen delivery facilitates antiviral vaccine success defined by effective immune protective responses against viral exposures. To improve severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigen delivery, a controlled biodegradable, stable, biocompatible, and nontoxic polymeric microsphere system was developed for chemically inactivated viral proteins. SARS-CoV-2 proteins encapsulated in polymeric microspheres induced robust antiviral immunity. The viral antigen-loaded microsphere system can preclude the need for repeat administrations, highlighting its potential as an effective vaccine. Statement of significance Successful SARS-CoV-2 vaccines were developed and quickly approved by the US Food and Drug Administration (FDA). However, each of the vaccines requires boosting as new variants arise. We posit that injectable biodegradable polymers represent a means for the sustained release of emerging viral antigens. The approach offers a means to reduce immunization frequency by predicting viral genomic variability. This strategy could lead to longer-lasting antiviral protective immunity. The current proof-of-concept multipolymer study for SARS-CoV-2 achieve these metrics. [PDF also includes a graphical abstract that can not be displayed here.

Multipolymer microsphere delivery of SARS-CoV-2 antigens

Effective antigen delivery facilitates antiviral vaccine success defined by effective immune protective re- sponses against viral exposures. To improve severe acute respiratory syndrome coronavirus-2 (SARS-CoV- 2) antigen delivery, a controlled biodegradable, stable, biocompatible, and nontoxic polymeric micro- sphere system was developed for chemically inactivated viral proteins. SARS-CoV-2 proteins encapsulated in polymeric microspheres induced robust antiviral immunity. The viral antigen-loaded microsphere sys- tem can preclude the need for repeat administrations, highlighting its potential as an effective vaccine

ISSN 2347-954X (Print) Screening of Social Anxiety Disorder in the Overweight and Obese Subjects Attending Obesity Clinic

Abstract: Obesity is a complex, chronic disorder with potentially serious medical, psychiatric and psychological morbidity. Society has created a widely accepted physical stereotype regarding thinness and beauty. The stigma of obesity, and particularly the prejudice and overt discrimination create enormous distress and hampering in social functioning. Obese individuals who seek treatment may suffer greater levels of social anxiety and are more likely to experience body image concerns, e.g. thinking of their body as "grotesque". So, my purpose is to screen for social phobia in obese patients. Research was carried out in the obesity clinic, The Ramakrishna Ashram Hospital, Rajkot. Subjects' general data were filled in Socio-demographic Performa sheet and The Social anxiety was screened by Mini-SPIN scale. Out of 100 patients, female patients (29%) were having more social anxiety than male patients. Regarding the correlation with severity of obesity, mild and severe obese patients were having more social anxiety than pre-obese and moderately obese patients (44 % and 50% respectively). In our study we found that obese patients are likely to have more social anxiety and it need to be addressed in comprehensive treatment plan of obesity

Amyloid-β specific regulatory T cells attenuate Alzheimer’s disease pathobiology in APP/PS1 mice

Abstract Background Regulatory T cells (Tregs) maintain immune tolerance. While Treg-mediated neuroprotective activities are now well-accepted, the lack of defined antigen specificity limits their therapeutic potential. This is notable for neurodegenerative diseases where cell access to injured brain regions is required for disease-specific therapeutic targeting and improved outcomes. To address this need, amyloid-beta (Aβ) antigen specificity was conferred to Treg responses by engineering the T cell receptor (TCR) specific for Aβ (TCRA β). The TCRAb were developed from disease-specific T cell effector (Teff) clones. The ability of Tregs expressing a transgenic TCRAβ (TCRAβ -Tregs) to reduce Aβ burden, transform effector to regulatory cells, and reverse disease-associated neurotoxicity proved beneficial in an animal model of Alzheimer’s disease. Methods TCRA β -Tregs were generated by CRISPR-Cas9 knockout of endogenous TCR and consequent incorporation of the transgenic TCRAb identified from Aβ reactive Teff monoclones. Antigen specificity was confirmed by MHC-Aβ-tetramer staining. Adoptive transfer of TCRAβ-Tregs to mice expressing a chimeric mouse-human amyloid precursor protein and a mutant human presenilin-1 followed measured behavior, immune, and immunohistochemical outcomes. Results TCRAβ-Tregs expressed an Aβ-specific TCR. Adoptive transfer of TCRAβ-Tregs led to sustained immune suppression, reduced microglial reaction, and amyloid loads. 18F-fluorodeoxyglucose radiolabeled TCRAβ-Treg homed to the brain facilitating antigen specificity. Reduction in amyloid load was associated with improved cognitive functions. Conclusions TCRAβ-Tregs reduced amyloid burden, restored brain homeostasis, and improved learning and memory, supporting the increased therapeutic benefit of antigen specific Treg immunotherapy for AD. Graphical Abstrac

Diagnostics for SARS-CoV-2 infections

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every corner of the globe, causing societal instability. The resultant coronavirus disease 2019 (COVID-19) leads to fever, sore throat, cough, chest and muscle pain, dyspnoea, confusion, anosmia, ageusia and headache. These can progress to life-threatening respiratory insufficiency, also affecting the heart, kidney, liver and nervous systems. The diagnosis of SARS-CoV-2 infection is often confused with that of influenza and seasonal upper respiratory tract viral infections. Due to available treatment strategies and required containments, rapid diagnosis is mandated. This Review brings clarity to the rapidly growing body of available and in-development diagnostic tests, including nanomaterial-based tools. It serves as a resource guide for scientists, physicians, students and the public at large

Pharmacotherapeutics of SARS-CoV-2 Infections

The COVID-19 pandemic has affected more than 38 million people world-wide by person to person transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therapeutic and preventative strategies for SARS-CoV-2 remains a significant challenge. Within the past several months, effective treatment options have emerged and now include repurposed antivirals, corticosteroids and virus-specific antibodies. The latter has included convalescence plasma and monoclonal antibodies. Complete viral eradication will be achieved through an effective, safe and preventative vaccine. To now provide a comprehensive summary for each of the pharmacotherapeutics and preventative strategies being offered or soon to be developed for SARS-CoV-2. Graphical abstract: [Figure not available: see fulltext.].</p