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1.
Rev Med Virol ; 33(1): e2398, 2023 01.
Article in English | MEDLINE | ID: mdl-36150052

ABSTRACT

The emergence of the SARS-CoV-2 Omicron variant (B.1.1.529) has created great global distress. This variant of concern shows multiple sublineages, importantly B.1.1.529.1 (BA.1), BA.1 + R346K (BA.1.1), and B.1.1.529.2 (BA.2), each with unique properties. However, little is known about this new variant, specifically its sub-variants. A narrative review was conducted to summarise the latest findings on transmissibility, clinical manifestations, diagnosis, and efficacy of current vaccines and treatments. Omicron has shown two times higher transmission rates than Delta and above ten times more infectious than other variants over a similar period. With more than 30 mutations in the spike protein's receptor-binding domain, there is reduced detection by conventional RT-PCR and rapid antigen tests. Moreover, the two-dose vaccine effectiveness against Delta and Omicron variants was found to be approximately 21%, suggesting an urgent need for a booster dose to prevent the possibility of breakthrough infections. However, the current vaccines remain highly efficacious against severe disease, hospitalisation, and mortality. Japanese preliminary lab data elucidated that the Omicron sublineage BA.2 shows a higher illness severity than BA.1. To date, the clinical management of Omicron remains unchanged, except for monoclonal antibodies. Thus far, only Bebtelovimab could sufficiently treat all three sub-variants of Omicron. Further studies are warranted to understand the complexity of Omicron and its sub-variants. Such research is necessary to improve the management and prevention of Omicron infection.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , SARS-CoV-2/genetics , Antibodies, Monoclonal , Breakthrough Infections , Antibodies, Viral , Antibodies, Neutralizing
2.
Burns ; 48(1): 59-68, 2022 02.
Article in English | MEDLINE | ID: mdl-34172326

ABSTRACT

INTRODUCTION: The hyper-catabolic state is a devastating pathophysiological response to severe injury, infection or burns. Nandrolone decanoate (ND) is a potent anabolic steroid have many clinical indications, but not investigated in burn injuries yet. PATIENTS AND METHODS: A prospective randomized control study included 40 burned patients who were treated in Burn unit from burn injuries ranged from 20 to 40%. Both groups are objectively assessed, clinically and laboratory during treatment period till full recovery from burns' injury. Recall assessment of the drug safety after many years is achieved. RESULTS: ND showed highly significant results supporting its use in combating catabolic insults in burns patient. Both clinical findings and laboratory findings are correlated and highly support the use of ND in burns as new effective and safe long-lasting indication. CONCLUSION: This study results showed preservation of lean body mass and protein partition, as well as the near normal nitrogen balance in burn patients. Study proposes that nandrolone decanoate could be used in safe and effective way to combat hypercatabolic impact in burn injury.


Subject(s)
Anabolic Agents , Burns , Nandrolone , Anabolic Agents/therapeutic use , Burns/drug therapy , Humans , Nandrolone/therapeutic use , Nandrolone Decanoate , Prospective Studies
3.
Int J Mol Sci ; 22(7)2021 Mar 30.
Article in English | MEDLINE | ID: mdl-33808215

ABSTRACT

Cutaneous squamous cell carcinomas (cSCCs) account for about 20% of keratinocyte carcinomas, the most common cancer in the UK. Therapeutic options for cSCC patients who develop metastasis are limited and a better understanding of the biochemical pathways involved in cSCC development/progression is crucial to identify novel therapeutic targets. Evidence indicates that the phosphoinositide 3-kinases (PI3Ks)/Akt pathway plays an important role, in particular in advanced cSCC. Questions remain of whether all four PI3K isoforms able to activate Akt are involved and whether selective inhibition of specific isoform(s) might represent a more targeted strategy. Here we determined the sensitivity of four patient-derived cSCC cell lines to isoform-specific PI3K inhibitors to start investigating their potential therapeutic value in cSCC. Parallel experiments were performed in immortalized keratinocyte cell lines. We observed that pan PI3Ks inhibition reduced the growth/viability of all tested cell lines, confirming the crucial role of this pathway. Selective inhibition of the PI3K isoform p110α reduced growth/viability of keratinocytes and of two cSCC cell lines while affecting the other two only slightly. Importantly, p110α inhibition reduced Akt phosphorylation in all cSCC cell lines. These data indicate that growth and viability of the investigated cSCC cells display differential sensitivity to isoform-specific PI3K inhibitors.


Subject(s)
Carcinoma, Squamous Cell/drug therapy , Phosphatidylinositol 3-Kinases/metabolism , Phosphoinositide-3 Kinase Inhibitors/pharmacology , Skin Neoplasms/drug therapy , Carcinoma, Squamous Cell/enzymology , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Survival/drug effects , Chromones/pharmacology , Humans , Imidazoles/pharmacology , Isoenzymes , Keratinocytes/drug effects , Keratinocytes/enzymology , Morpholines/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Skin Neoplasms/enzymology , Skin Neoplasms/pathology , TOR Serine-Threonine Kinases/antagonists & inhibitors , TOR Serine-Threonine Kinases/metabolism , Thiazoles/pharmacology , Thiazolidinediones/pharmacology
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