The efficacy and safety of Nigella sativa in the management of osteoarthritis: A systematic review.

Background and Aims: Osteoarthritis (OA) is one of the most common debilitating diseases among the aging population. Nigella sativa is one potential treatment for OA. Here, we sought to evaluate the efficacy and safety of Nigella sativa for treating patients with OA. Methods: PubMed, Scopus, Embase, and Web of Science were searched up to October 20, 2022. The primary outcome was changes in the pain score after receiving Nigella sativa or control agents based on the results of randomized controlled trials (RCTs). The secondary outcome was set as the frequency of adverse events reported during the follow-up period. Results: Six RCTs involving a total of 370 patients with knee OA were included in the present systematic review. Among the four screened studies, the topical administration of Nigella sativa oil was found to be more effective than the placebo in relieving pain in three trials. Additionally, the oral use of Nigella sativa oil was assessed in two trials, and an improvement in pain score relative to placebo was documented in only one of the studies. Also, the trial that evaluated the effectiveness of Nigella sativa oral capsules did not demonstrate any difference in pain reduction between the intervention and placebo groups. Overall, either topical or oral administration of Nigella sativa was well tolerated, and no serious adverse events were reported. Conclusion: Nigella sativa is generally safe, but conflicting findings from low-quality studies hinder the ability to make clinical recommendations for or against treating OA. Robust trials are needed for informed decisions.

Safety and efficacy of cladribine in multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Previously, several studies investigated the effect of cladribine among patients with multiple sclerosis (MS) as a treatment option. Due to the contradictory results of previous studies regarding the efficacy and safety of cladribine in the MS population, we aimed to conduct a systematic review and meta-analysis by including clinical trials and observational studies in terms of having more confirmative results to make a general decision. METHODS: The three databases including PubMed, Scopus, and Web of Science were comprehensively searched in May 2022. We included the studies that investigated the efficacy and safety of cladribine in patients with MS. Eligible studies have to provide sufficient details on MS diagnosis and appropriate follow-up duration. We investigated the efficacy of cladribine with several outcomes including Expanded Disability Status Scale (EDSS) change, progression-free survival (PFS), relapse-free survival (RFS), and MRI-free activity survival (MFAS). RESULTS: After two-step reviewing, 23 studies were included in our qualitative and quantitative synthesis. The pooled SMD for EDSS before and after treatment was - 0.54 (95%CI: - 1.46, 0.39). Our analysis showed that the PFS after cladribine use is 79% (95%CI 71%, 86%). Also, 58% of patients with MS who received cladribine remained relapse-free (95%CI 31%, 83%). Furthermore, the MFAS after treatment was 60% (95%CI 36%, 81%). Our analysis showed that infection is the most common adverse event after cladribine treatment with a pooled prevalence of 10% (95%CI 4%, 18%). Moreover, the pooled prevalence of infusion-related adverse events was 9% (95%CI 4%, 15%). Also, the malignancies after cladribine were present in 0.4% of patients (95%CI 0.25%, 0.75%). CONCLUSION: Our results showed acceptable safety and efficacy for cladribine for the treatment of MS except in terms of reducing EDSS. Combination of our findings with the results of previous studies which compared cladribine to other disease-modifying therapies (DMTs), cladribine seems to be a safe and effective drug in achieving better treatment for relapsing-remitting MS (RRMS) patients.

Targeted co-delivery of methotrexate and chloroquine via a pH/enzyme-responsive biocompatible polymeric nanohydrogel for colorectal cancer treatment.

Application of conventional chemotherapy regardless of its unique effectiveness have been gradually being edged aside due to limited targeting capability, lack of selectivity and chemotherapy-associated side effects. To this end, colon-targeted nanoparticles via combination therapy have shown great therapeutic potential against cancer. Herein, pH/enzyme-responsive biocompatible polymeric nanohydrogels based on poly(methacrylic acid) (PMAA) containing methotrexate (MTX) and chloroquine (CQ) were fabricated. PMAA-MTX-CQ exhibited high drug loading capacity of which MTX was 4.99% and was CQ 25.01% and displayed pH/enzyme-triggered drug release behavior. Higher CQ release rate (76%) under simulated acidic microenvironment of tumor tissue whereas 39% of CQ was released under normal physiological conditions. Intestinally, MTX release was facilitated in the presence of proteinase K enzyme. TEM image demonstrated spherical morphology with particle size of less than 50 nm. In vitro and in vivo toxicity assessments indicated that developed nanoplatforms possessed great biocompatibility. These nanohydrogels did not cause any adverse effects against Artemia Salina and HFF2 cells (around 100% cell viability) which highlight the safety of prepared nanohydrogels. There was no death in mice received different concentrations of nanohydrogel through oral administration and less than 5% hemolysis was found in red blood cells incubated with PMAA nanohydrogels. In vitro anti-cancer results showed that combination therapy based on PMAA-MTX-CQ can effectively suppress the growth of SW480 colon cancer cells (29% cell viability) compared to monotherapy. Altogether, these findings suggest that pH/enzyme-responsive PMAA-MTX-CQ could effectively inhibit cancer cell growth and progression via site-specific delivery of its cargo in a safe and controlled manner.

Acute disseminated encephalomyelitis (ADEM) following COVID-19 vaccination: A systematic review.

BACKGROUND: Although global vaccination against COVID-19 infection has its excellence, potential side effects are yet of concern. Several lines of evidence have proposed ADEM occurrence after SARS-CoV-2 infection. Moreover, a large number of case reports and case series have also suggested the casual association between ADEM and COVID-19 vaccination. To better understand the development of ADEM following COVID-19 vaccination and its potential association, we aimed to systematically review ADEM cases reported after COVID-19 vaccination. METHODS: We conducted a comprehensive systematic search using three databases including PubMed, Scopus, and Web of Science. Studies that reported ADEM after COVID-19 vaccination were eligible to include in our study. Observational studies, case reports, and case series which reported cases of ADEM with sufficient detail to confirm clinical diagnosis following COVID-19 vaccination were eligible to enter our study. RESULTS: Twenty studies were included in our systematic review after the abstract and full-text screening with a total of 54 cases. Among included patients, 45 (85.1 %) developed ADEM after the first dose of the COVID-19 vaccine, and seven (12.9 %) cases experienced ADEM after the second dose. The median time interval between vaccination and neurological symptoms was 14 days which ranged from 12 h to 63 days. Twelve (22.2 %) patients experienced symptoms of muscle weakness, ten (18.5 %) presented unconsciousness, nine (16.6 %) patients had urinary complaints, nine (16.6 %) had visual impairments, and five (9.2 %) experienced a seizure. After treatments, four (13.8 %) patients died. Forty-six patients had clinical improvement (85.1 %), also improvement in brain MRI was observed among 44 (81.4 %) patients. CONCLUSION: In conclusion, it is not clear that ADEM could be a potential complication of COVID-19 vaccination based on the current evidence and further studies are needed. However, this rare condition should not trigger stopping the mass vaccination programs since the only way to eradicate the current pandemic of COVID-19 is to extend the number of immunized people.

Efficacy of tocilizumab in the treatment of COVID-19: An umbrella review.

Tocilizumab is an interleukin (IL)-6 receptor inhibitor that has been proposed as a therapeutic agent for treating coronavirus disease 2019 (COVID-19). The aim of this umbrella review was to determine the efficacy of tocilizumab in treating COVID-19, and to provide an overview of all systematic reviews on this topic. We systematically searched PubMed, Scopus, the Web of Science collection, the Cochrane library, Epistemonikos, and Google Scholar, as well as the medRxiv preprint server. These databases were searched up to 30 September 2021, using the following keywords: 'SARS-CoV-2', 'COVID-19', 'tocilizumab', 'RHPM-1', 'systematic review', and 'meta-analysis'. Studies were included if they were systematic reviews (with or without meta-analysis) investigating the efficacy or safety of tocilizumab in confirmed COVID-19 patients. The AMSTAR 2 checklist was used to assess quality of the included articles, while publication bias was examined using Egger's test. A total of 50 eligible systematic reviews were included. The pooled estimates showed significant reductions in clinical failure (risk ratio (RR) 0.75; 95% confidence interval (CI), 0.61-0.93), deaths (RR 0.78; 95%CI, 0.71-0.85) and the need for mechanical ventilation (RR 0.77; 95%CI, 0.64-0.92) for those receiving tocilizumab compared with the control group. Also, an emerging survival benefit was demonstrated for those who received tocilizumab, over those in the control group (adjusted hazard ratio (aHR) 0.52; 95%CI, 0.43-0.63). In addition, tocilizumab substantially increased the number of ventilator-free days, compared with the control treatments (weighted mean difference (WMD) 3.38; 95%CI, 0.51-6.25). Furthermore, lymphocyte count (WMD 0.26 × 109 /L; 95%CI, 0.14-0.37), IL-6 (WMD 176.99 pg/mL; 95%CI, 76.34-277.64) and D-dimer (WMD 741.08 ng/mL; 95%CI, 109.42-1372.75) were all significantly elevated in those receiving tocilizumab. However, the level of lactate dehydrogenase (LDH) (WMD -30.88 U/L; 95%CI, -51.52, -10.24) and C-reactive protein (CRP) (WMD -104.83 mg/L; 95%CI, -133.21, -76.46) were both significantly lower after treatment with tocilizumab. Tocilizumab treatment reduced the risk of intubation, mortality and the length of hospital stay, without increasing the risk of superimposed infections in COVID-19 patients. Therefore, tocilizumab can be considered an effective therapeutic agent for treating patients with COVID-19.

Natural killer cells and acute myeloid leukemia: promises and challenges.

Acute myeloid leukemia (AML) is considered as one of the most malignant conditions of the bone marrow. Over the past few decades, despite substantial progresses in the management of AML, relapse remission remains a major problem. Natural killer cells (NK cells) are known as a unique component of the innate immune system. Due to swift tumor detection, distinct cytotoxic action, and extensive immune interaction, NK cells have been used in various cancer settings for decades. It has been a growing knowledge of therapeutic magnitudes ranging from adoptive NK cell transfer to chimeric antigen receptor NK cells, aiming to achieve better therapeutic responses in patients with AML. In this article, the potentials of NK cells for treatment of AML are highlighted, and challenges for such therapeutic methods are discussed. In addition, the clinical application of NK cells, mainly in patients with AML, is pictured according to the existing evidence.

SARS-CoV-2 Omicron (B.1.1.529) Variant: No Time to Wait!

On November 26th, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), B.1.1.529, was designated by the World Health Organization (WHO), named Omicron, and classified as a variant of concern (VOC). The news raised an international alarm about a new wave of coronavirus disease 2019 (Covid-19) outbreak, since Omicron has a large group of mutations which may affect the way it spread, cause disease, and escape from the immunity. Therefore, it is essential to take a closer look at how it has emerged, how it may sustain the pandemic, and how we can act correspondingly, both nationally and internationally, to help control the spreading of the disease.

Synaptic plasticity and depression: the role of miRNAs dysregulation.

BACKGROUND: MicroRNAs (miRNAs) have been recently shown to exert several functional roles in the development and function of neurons. Moreover, numerous miRNAs are present in high abundance in presynaptic and postsynaptic sites regulating synaptic plasticity and activity through different mechanisms. METHODS: We searched PubMed and Google Scholar databases with key words "Synaptic plasticity", "miRNA" and "major depressive disorder. RESULTS: Synaptic plasticity has an essential role in the ability of the brain to integrate transitory experiences into constant memory traces. Thus, it participates in the development of neuropsychiatric diseases such as major depressive disorder (MDD). Most notably, MDD-related alterations in synaptic function have been found to be closely related with abnormal expression of miRNAs. CONCLUSIONS: Several miRNAs such as miR-9-5p, miR-204-5p, miR-128-3, miR-26a-3p, miR-218, miR-22-3p, miR-124-3p, miR-136-3p, miR-154-5p, miR-323a-3p, miR-425-5p, miR-34a, miR-137, miR-204-5p, miR-99a, miR-134, miR-124-3p and miR-3130-5p have been shown to be involved in the regulation of synaptic plasticity in the context of MDD. In the current review, we elaborate the role of miRNAs in regulation of this important neuronal feature in MDD.

SARS-CoV-2 Omicron variant: Why global communities should take it seriously?

INTRODUCTION: In November 26th, 2021 a new strain of SARS-CoV-2 was designated by the World Health Organization as a variant of concern and named Omicron. The news broadcasted a global wave of panic and anxiety while many, like 2 years ago, were making themselves ready for the holiday season. After almost a month of its designation, countries from all 6 continents have been reported Omicron from their genomic sequences. This triggered an international alarm about a new era in the Covid-19 pandemic, where despite the vast amount of vaccinations, a surge in new cases and hospitalizations are reported from all over the world. METHODS: Scientific literature published from November 26, 2021 to March 21, 2022 have been searched and retrieved by using "SARS-COV-2", "Omicron", "B.1.1.529", "Covid-19", and "global community" keywords from "PubMed", "Web o "Google Scholar", and "MedRxiv" databases. RESULTS: Omicron have been evolved to spread faster than previous variants of concern, but it infects people lesser than other variants, Delta for example. Omicron can also escape vaccine-induced immunity more than previous SARS-CoV-2 variants. DISCUSSION: Despite possible lower lethal risks than previous strains, Omicron may provide populations with a higher community transmission and a higher hospitalization load, which potentially overwhelm already exhausted health care systems. Therefore, we need to get used to the "New Normal" and maintain health recommendations to help decrease spreading of the virus and buy more time for the scientists to dive deeper into potential ways of tackling Covid-19, more than ever.

Depresssion, anxiety and other cognitive consequences of social isolation: Drug and non-drug treatments.

OBJECTIVE: During the COVID-19 pandemic, quarantine and staying at home is advised. The social relationship between people has become deficient, and human social isolation (SI) has become the consequence of this situation. It was shown that SI has made changes in hippocampal neuroplasticity, which will lead to poor cognitive function and behavioural abnormalities. There is a connection between SI, learning, and memory impairments. In addition, anxiety-like behaviour and increased aggressive mood in long-term isolation have been revealed during the COVID-19 outbreak. METHODS: Term searches was done in Google Scholar, Scopus, ScienceDirect, Web of Science and PubMed databases as well as hand searching in key resource journals from 1979 to 2020. RESULTS: Studies have shown that some drug administrations may positively affect or even prevent social isolation consequences in animal models. These drug treatments have included opioid drugs, anti-depressants, Antioxidants, and herbal medications. In addition to drug interventions, there are non-drug treatments that include an enriched environment, regular exercise, and music. CONCLUSION: This manuscript aims to review improved cognitive impairments induced by SI during COVID-19.

Contribution of miRNAs and lncRNAs in osteogenesis and related disorders.

Non-coding RNAs have been found to regulate several developmental processes among them is osteogenesis. Although these transcripts have several distinct classes, two classes i.e. microRNAs and long non-coding RNAs have attained more attention. These transcripts regulate intramembranous as well as endochondral ossification processes. The effects of microRNAs on osteogenesis are mostly mediated through modulation of Wnt/ß-catenin and TGFß/BMP pathways. Long non-coding RNAs can directly affect expression of these pathways or osteogenic transcription factors. Moreover, they can serve as a molecular sponge for miRNAs. MALAT1/miR-30, MALAt1/miR-214, LEF1-AS1/miR-24-3p, MCF2L-AS1/miR-33a, MSC-AS1/miR-140-5p and KCNQ1OT1/miR-214 are examples of such kind of interaction between lncRNAs and miRNAs in the context of osteogenesis. In the current paper, we explain these two classes of non-coding RNAs in the osteogenesis and related disorders.