A Review on Role of Inflammation in Coronavirus Disease.

The respiratory illness known as COVID-19 is caused by the novel coronavirus, SARS-CoV-2. While the precise pathogenic mechanism of COVID-19 remains unclear, the occurrence of a cytokine storm subsequent to viral infection plays a pivotal role in the initiation and advancement of the disease. The infection of SARS-CoV-2 induces a state of immune system hyperactivity, leading to an excessive production of inflammatory cytokines. Consequently, the identification of the various signaling pathways implicated in the inflammation induced by COVID-19 will enable researchers to investigate new targets for therapeutic intervention.

The Important Role of Interleukin-2 in COVID-19.

There is controversial literature about the effects of the interleukin-2 (IL-2) cytokine family in COVID-19 pathogenesis and immunity. So we aimed to identify the potential in the role of the IL-2 family in COVID-19. A narrative review search was done through online databases, including PubMed, Scopus, and Web of Science. The search deadline was up to December 2022. We applied no time limits for the searching strategy. After retrieving articles from the databases, the authors summarized the data into two data extraction tables. The first data extraction table described the changes in the IL-2 cytokine family in COVID-19 and the second table described the therapeutic interventions targeting IL-2 family cytokines. The results of the literature on the role of the IL-2 cytokine family do not show a singular rule. IL-2 cytokine family can change during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some studies suggest that IL-2 cytokine family rise during the infection and cause severe inflammatory response and cytokine storm. These cytokines are shown to be increased in immunocompromised patients and worsen their prognosis. In individuals without underlying disease, the upregulation of the IL-2 family shows the clinical outcome of the disease and rises with disease severity. However, some other studies show that these cytokines do not significantly change. IL-2 cytokine family is mostly upregulated in healthy individuals who had vaccination, but immunocompromised patients did not show significant changes after a single dose of vaccines, which shows that these patients need booster doses for efficient immunity. IL-2 cytokine family can also be used as immunotherapy agents in COVID-19.

Dendritic cells and natural killer cells: The road to a successful oncolytic virotherapy.

Every type of cancer tissue is theoretically more vulnerable to viral infection. This natural proclivity has been harnessed as a new anti-cancer therapy by employing oncolytic viruses (OVs) to selectively infect and destroy cancer cells while providing little or no harm with no toxicity to the host. Whereas the primary oncolytic capabilities of OVs initially sparked the greatest concern, the predominant focus of research is on the association between OVs and the host immune system. Numerous OVs are potent causal agents of class I MHC pathway-related chemicals, enabling early tumor/viral immune recognition and cytokine-mediated response. The modified OVs have been studied for their ability to bind to dendritic cells (DCs) by expressing growth factors, chemokines, cytokines, and defensins inside the viral genome. OVs, like reovirus, can directly infect DCs, causing them to release chemokines and cytokines that attract and excite natural killer (NK) cells. In addition, OVs can directly alter cancer cells' sensitivity to NK by altering the expression levels of NK cell activators and inhibitors on cancerous cells. Therefore, NK cells and DCs in modulating the therapeutic response should be considered when developing and improving future OV-based therapeutics, whether modified to express transgenes or used in combination with other drugs/immunotherapies. Concerning the close relationship between NK cells and DCs in the potential of OVs to kill tumor cells, we explore how DCs and NK cells in tumor microenvironment affect oncolytic virotherapy and summarize additional information about the interaction mentioned above in detail in this work.

Nanoengineered myogenic scaffolds for skeletal muscle tissue engineering.

Extreme loss of skeletal muscle overwhelms the natural regenerative capability of the body, results in permanent disability and substantial economic burden. Current surgical techniques result in poor healing, secondary injury to the autograft donor site, and incomplete recuperation of muscle function. Most current tissue engineering and regenerative strategies fail to create an adequate mechanical and biological environment that enables cell infiltration, proliferation, and myogenic differentiation. In this study, we present a nanoengineered skeletal muscle scaffold based on functionalized gelatin methacrylate (GelMA) hydrogel, optimized for muscle progenitors' proliferation and differentiation. The scaffold was capable of controlling the release of insulin-like growth factor 1 (IGF-1), an important myogenic growth factor, by utilizing the electrostatic interactions with LAPONITE® nanoclays (NCs). Physiologically relevant levels of IGF-1 were maintained during a controlled release over two weeks. The NC was able to retain 50% of the released IGF-1 within the hydrogel niche, significantly improving cellular proliferation and differentiation compared to control hydrogels. IGF-1 supplemented medium controls required 44% more IGF-1 than the comparable NC hydrogel composites. The nanofunctionalized scaffold is a viable option for the treatment of extreme muscle injuries and offers scalable benefits for translational interventions and the growing field of clean meat production.

3D-Printed Hydrogel-Filled Microneedle Arrays.

Microneedle arrays (MNAs) have been used for decades to deliver drugs transdermally and avoid the obstacles of other delivery routes. Hydrogels are another popular method for delivering therapeutics because they provide tunable, controlled release of their encapsulated payload. However, hydrogels are not strong or stiff, and cannot be formed into constructs that penetrate the skin. Accordingly, it has so far been impossible to combine the transdermal delivery route provided by MNAs with the therapeutic encapsulation potential of hydrogels. To address this challenge, a low cost and simple, but robust, strategy employing MNAs is developed. These MNAs are formed from a rigid outer layer, 3D printed onto a conformal backing, and filled with drug-eluting hydrogels. Microneedles of different lengths are fabricated on a single patch, facilitating the delivery of various agents to different tissue depths. In addition to spatial distribution, temporal release kinetics can be controlled by changing the hydrogel composition or the needles' geometry. As a proof-of-concept, MNAs are used for the delivery of vascular endothelial growth factor (VEGF). Application of the rigid, resin-based outer layer allows the use of hydrogels regardless of their mechanical properties and makes these multicomponent MNAs suitable for a range of drug delivery applications.

In Vivo Printing of Nanoenabled Scaffolds for the Treatment of Skeletal Muscle Injuries.

Extremity skeletal muscle injuries result in substantial disability. Current treatments fail to recoup muscle function, but properly designed and implemented tissue engineering and regenerative medicine techniques can overcome this challenge. In this study, a nanoengineered, growth factor-eluting bioink that utilizes Laponite nanoclay for the controlled release of vascular endothelial growth factor (VEGF) and a GelMA hydrogel for a supportive and adhesive scaffold that can be crosslinked in vivo is presented. The bioink is delivered with a partially automated handheld printer for the in vivo formation of an adhesive and 3D scaffold. The effect of the controlled delivery of VEGF alone or paired with adhesive, supportive, and fibrilar architecture has not been studied in volumetric muscle loss (VML) injuries. Upon direct in vivo printing, the constructs are adherent to skeletal muscle and sustained release of VEGF. The in vivo printing of muscle ink in a murine model of VML injury promotes functional muscle recovery, reduced fibrosis, and increased anabolic response compared to untreated mice. The in vivo construction of a therapeutic-eluting 3D scaffold paves the way for the immediate treatment of a variety of soft tissue traumas.

Levofloxacin-containing triple therapy versus bismuth-based quadruple therapy as regimens for second line anti- Helicobacter pylori.

BACKGROUND: Although the prevalence of Helicobacter pylori infection decreased following the hygiene promotion and application of proper anti- H.pylori treatments, unfortunately gradual increase is reported in treatment failure; hence, application of a proper treatment regimen as a second-line therapy is of great importance. METHODS: In the current randomized, clinical trial, a total of 120 patients with peptic ulcers who failed to respond to treatment were enrolled. In the OLA group, a regimen of omeprazole 40 mg/day, levofloxacin 1 g/day, and amoxicillin 2 g/ day was prescribed; however, a regimen of omeprazole 40 mg/day, bismuth sub-citrate 480 mg/day, furazolidone 400 mg/day, and amoxicillin 2 g/day was administered to the OFAB group. Both groups were treated for 2 weeks, and 6 weeks after the treatment, the urea breath test (UBT) was performed in the subjects. Collected data were analyzed with SPSS Version 18. At the end, 58 patients in group OLA and 57 patients in the OFAB group were analyzed. RESULTS: According to the results of the current study, 96.7% of the subjects in the OLA and 95% in the OFAB groups completed the treatment course and the eradication rates were 86.7% and 78.3% in the OLA and OFAB groups, respectively (P=0.23). Treatment side effects were observed in 51.7% and 11.7% of the subjects in the OLA and OFAB groups, respectively (P<0.01). CONCLUSION: Both regimens were applicable as the second-line therapy due to insignificant difference between the results of the 2 groups; however, OLA regimen was superior to OFAB, due to lower side effects.

Prevalence of class 1 integron among multidrug-resistant Acinetobacter baumannii in Tabriz, northwest of Iran.

Integrons are associated with a variety of gene cassettes, which confer resistance to multiple classes of antibacterial drugs. In this study we tested the frequency of class 1 and 2 integrons among multidrug-resistant Acinetobacter baumannii (MDRAB) clinical isolates. One hundred clinical isolates of A. baumannii were screened for carriage of class 1 and 2 integrons by PCR method. Results showed that seventy four (92.5%) of 80 MDRAB carried class 1 integron. Integron-positive isolates were statistically more resistant to aminoglycoside, quinolone and beta-lactam compounds except for cefepime. This is the first report of class 1 integrons in MDRAB isolates in northwest Iran.

High prevalence of metallo-beta-lactamase-producing acinetobacter baumannii in a teaching hospital in Tabriz, Iran.

Metallo-beta-lactamase (MBL)-producing Acinetobacter baumannii has become a growing therapeutic concern worldwide. The aims of this study were to evaluate the antimicrobial susceptibility of A. baumannii isolates and to determine the prevalence of MBL genes among carbapenem non-susceptible isolates. During a period of 16 months (March 2008-June 2009), 100 isolates of A. baumannii were collected from different clinical specimens of inpatients admitted to the largest teaching hospital in the northwest of Iran. All isolates were tested for antimicrobial susceptibility by Kirby-Bauer disk diffusion method. Carbapenem non-susceptible isolates were further screened for production of MBL by Etest and were then subjected to PCR for detection of MBL genes of types bla(IMP) and bla(VIM). Among 63 carbapenem (imipenem and meropenem) non-susceptible isolates of A. baumannii, 31 (49%) were found to be MBL producers. Of 31 MBL-producing isolates, 19 (61%) carried the bla(IMP) gene and 9 (29%) carried the bla(VIM) gene. All MBL-producing isolates were multidrug resistant. This is the first report of IMP and VIM types among MBL-producing A. baumannii in Iran.