Ralstonkejser0243

Extracellular vesicles derived from mesenchymal stromal cells (MSC-EVs) are gaining interest for medical purposes. The promising therapeutic effects exhibited in both preclinical and clinical studies have suggested that they may become an alternative for certain applications to cell-based therapies, which are subjected to stricter regulations. The commercial exploitation of these candidates requires a proper patent strategy from both the industry and public research organizations. Here, we performed a global patent literature analysis to identify key players and therapeutic applications in the field. Our results showed an increasing rate of patent publications since 2009, with Asia (specifically China) leading the patenting activity. The therapeutic use of MSC-EVs within patent literature covers a wide range of diseases, in which "Dermal and Wounds," "Neurology" and "Cardiovascular" are the main therapeutic areas. Moreover, most of these patents include "productby- process" claims, since the therapeutic effects of MSC-EVs could be influenced by their manufacturing process. Our results followed scientific and clinical literature trends.

The prediction of pathological responses for locally advanced rectal cancer using magnetic resonance imaging (MRI) after neoadjuvant chemoradiotherapy (CRT) is a challenging task for radiologists, as residual tumor cells can be mistaken for fibrosis. Texture analysis of MR images has been proposed to understand the underlying pathology.

This study aimed to assess the responses of lesions to CRT in patients with locally advanced rectal cancer using the first-order textural features of MRI T2-weighted imaging (T2-WI) and apparent diffusion coefficient (ADC) maps.

Forty-four patients with locally advanced rectal cancer (median age 57 years) who underwent MRI before and after CRT were enrolled in this retrospective study. The first-order textural parameters of tumors on T2-WI and ADC maps were extracted. The textural features of lesions in pathologic complete responders were compared to partial responders using Student's t- or Mann-Whitney U tests. A comparison of textural features before and after CRT for thin this dataset.

Integrase strand transfer inhibitors (INSTIs) are currently the standard of practice for first-line HIV therapy for most patients. We evaluated the mutations associated with INSTI resistance in naive HIV-1 infected patients and treated them with antiretrovirals (ART).

The study, conducted in the 2018 - 2020 period, included 50 ART-naïve patients, 69 INSTI free ART-experienced patients, and 82 INSTI-experienced patients. INSTI resistance mutations were interpreted using the Stanford University HIVdb Program algorithm.

INSTI resistance was not detected in ART naïve patients. At least one INSTI resistance mutation was detected in 10% of the INSTI-free patients and 29% of the INSTI-treated patients. Major INSTI-mutations E138K, Y143R, S147G, Q148R, N155H, and E157Q were found in raltegravir. Additional mutations, E92Q, E138K, G140A, S147G, and Q148R were found in elvitegravir; E192Q, E138K/T, G140A/S, S147G, Q148H/R, N155H, E157Q were found in dolutegravir (DTG) experienced patients. According to all drug cn be initiated in the future, and reduced DTG susceptibility should be carefully monitored and investigated.

The COVID-19 pandemic has substantially changed lives and presented several barriers to health services. HIV care continuum needs a high rate of diagnosis, effective treatment, and sustained suppression of viral replication. The COVID-19 pandemic has affected these three steps of HIV care. This study investigated the characteristics of newly diagnosed patients living with HIV/AIDS (PLWH) during the COVID pandemic and compared them with those before the pandemic.

All newly diagnosed patients in three HIV healthcare centers, in Istanbul, Turkey, were included in the study. The pandemic period included April 1, 2020, to April 1, 2021, and the prepandemic period included March 1, 2019, to March 1, 2020.

756 patients were diagnosed with HIV/AIDS. In the pandemic period, this figure was 58% less 315. Patients in the pre-pandemic and pandemic period had comparable age and gender distributions. PLWH diagnosed in the pandemic period had higher rates of low CD4 cells low CD4 (<350 cells /mm3) was measured in 2e during the pandemic. Sexual behaviors may have changed during the COVID-19 pandemic, leading to HIV transmission restriction. Lower CD4 counts among the newly diagnosed PLWH suggest that admittance to health care is late and a significant portion of PLWH remain undiagnosed.Ribonucleases (RNases) are a superfamily of enzymes that have been extensively studied since the 1960s. For a long time, this group of secretory enzymes was studied as an important model for protein chemistry such as folding, stability, and enzymatic catalysis. Since it was discovered that RNases displayed cytotoxic activity against several types of malignant cells, recent investigation has focused mainly on the biological functions and medical applications of engineered RNases. In this review, we describe the structures, functions, and mechanisms of antitumor activity of RNases. They operate at the crossroads of transcription and translation, preferentially degrading tRNA. As a result, this inhibits protein synthesis, induces apoptosis, and causes the death of cancer cells. This effect can be enhanced thousands of times when RNases are conjugated with monoclonal antibodies. Such combinations, called immunoRNases, have demonstrated selective antitumor activity against cancer cells both in vitro and in animal models. This review summarizes the current status of engineered RNases and immunoRNases as promising novel therapeutic agents for different types of cancer. Also, we describe our experimental results from published or previously unpublished research and compare them with other scientific information.Disorders of the brain constitute the most debilitating situation globally with increased mortality rates every year, while brain physiology and cumbersome drug development processes exacerbate this. Although blood-brain barrier (BBB) and its components are important for brain protection, their complexity creates major obstacles for brain drug delivery, and the BBB is the primary cause of treatment failure, leading to disease progression. Therefore, developing an ideal platform that can predict the behavior of a drug delivery system in the brain at the early development phase is extremely crucial. In this direction, in the last two decades, numerous in vitro BBB models have been developed and investigated by researchers to understand the barrier properties and how closely the in vitro models mimic in vivo BBB. In-vitro BBB models mainly involve the culture of endothelial cells or their coculture with other perivascular cells either in two or three-dimensional platforms. In this article, we have briefly summarized the fundamentals of BBB and outlined different types of in vitro BBB models with their pros and cons. Based on the available reports, no model seems to be robust that can truly mimic the entire properties of the in vivo BBB microvasculature. However, human stem cells, coculture and threedimensional models have been found to mimic the complexity of the barrier integrity not completely but more precisely than other in vitro models. More studies aiming towards combining these models together would be needed to develop an ideal in vitro model that can overcome the existing limitations and unravel the mysterious BBB vasculature.

Neuroinflammation occurring as a result of oxidative and nitrosative stress is associated with various neurological disorders and involves generation of pro-inflammatory cytokines as well as activation of microglia. Dietary phytochemicals are a safer and valuable adjunct neurotherapeutic agents which can be added to the therapeutic regimen. These compounds provide neuroprotection by modulation of various signaling pathways.

Naringenin (NGN) is a phytochemical having low oral bioavailability because of poor solubility, and adding to this limitation is enhanced efflux by P-glycoprotein transporters in neuroinflammatory diseases.

Hence, as a solution for these limitations, Naringenin encapsulated poly-lactic-co-glycolic acid (PLGA) nanocarriers were developed utilizing nanoprecipitation technique and were coated with 1% glutathione (GSH) and 1% Tween 80 to enhance brain delivery.

Coated as well as uncoated NGN-PLGA nanoparticles (NGN-PLGA-NPs) were spherical, monodisperse, stable, non-toxic with a particle size of less than 200 nm and negative zeta-potential values, 80% entrapment efficiency, and sustained drug release of 81.8% (uncoated), 80.13 and 78.43% (coated) respectively in 24 hours. FT-IR, DSC, PXRD, and NMR confirmed the drug encapsulation and coating over nanoparticles. In-vivo brain uptake showed greater fluorescence intensity of the coated nanoparticles in the brain than uncoated nanoparticles. In addition, there was a 2.33 fold increase in bioavailability after coating compared to naringenin suspension and enhanced brain uptake.

Present studies indicate sustained and targeted brain delivery of Naringenin via the ligand-coated delivery system by inhibition of enhanced P-glycoprotein (P-gp) efflux occurring due to neuroinflammation in Autism Spectrum Disorders.

Present studies indicate sustained and targeted brain delivery of Naringenin via the ligand-coated delivery system by inhibition of enhanced P-glycoprotein (P-gp) efflux occurring due to neuroinflammation in Autism Spectrum Disorders.

Hydrophilic drugs are poor applicants for brain targeting via oral route due to the presence of a blood-brain barrier that allows only small lipophilic molecules to freely access the brain. Due to unique anatomical connections between the nasal cavity and the brain, intranasal administration can be explored for drug delivery to the brain directly that circumvents the blood-brain barrier too.

Zolmitriptan is a widely used antimigraine drug, and its brain targeting by nasal route in the form of mucoadhesive nanoparticles is more effective in migraine treatment as it provides fast relief and good bioavailability as compared to its oral drug delivery. In the present study, zolmitriptan mucoadhesive nanoparticles were prepared to improve the bioavailability and brain targeting for the better management of Migraine attacks.

The mucoadhesive polymeric nanoparticles of zolmitriptan were formulated by a modified ionic gelation method using thiolated chitosan. The pharmacokinetic parameters were counted in male Wose-to-brain transport by zolmitriptan nanoparticles as compared to oral delivery in male Wistar rats. A significant increase in the tolerance capacity of animals to bright light and a fall in the number of stretching in mice suggested the better management of migraine-associated symptoms by the zolmitriptan nanoparticles.

Thus, the present study confers the significance of nasal drug delivery for brain targeting of zolmitriptan nanoparticles for the treatment of migraine.

Thus, the present study confers the significance of nasal drug delivery for brain targeting of zolmitriptan nanoparticles for the treatment of migraine.