Modulation of salivary ICAM-1 and SIRT1 by disease modifying drugs in undepressed relapsing-remitting multiple sclerosis patients.

BACKGROUND: The pathophysiology of Multiple Sclerosis (MS) is multifactorial where the correlation between inflammation and MS is evident. Adhesion molecules such as Intercellular adhesion molecule-1 (ICAM-1) are implicated in MS. SIRT1 is a member of surtins family that play a protective role in neurodegenerative and inflammatory diseases. Although previously studied in Relapsing-Remitting Multiple Sclerosis (RRMS) patients, however the salivary expression of ICAM-1 and SIRT1 have not been yet studied in patients receiving fingolimod or interferon-ß. Therefore, the present research aimed to investigate the expression of salivary ICAM-1 and SIRT1 in RRMS patients treated with fingolimod or interferon-ß compared to controls. METHODS: RRMS patients attending the neurology department of AL-Bashir Hospital were recruited. Patients' demographics, clinical information, and psychiatric status were evaluated (depression, anxiety and stress). Afterward, matched controls were recruited, then unstimulated whole saliva was obtained from the participants. The salivary expression of ICAM-1 and SIRT1 was investigated using western blot and normalized with ß-actin. RESULTS: Data were analyzed from 53 participants: 26 on fingolimod, 14 on interferon-ß, and 13 control. The interferon-ß treated patients showed a significantly (p < 0.001) higher ICAM-1 expression and lower SIRT1 expression (p < 0.05) compared to the control. Levels of ICAM-1 and SIRT1 did not vary between fingolimod and control. CONCLUSION: ICAM-1 and SIRT1 expression might be affected with fingolimod or INF- ß treatment which should be investigated more in the future.

Monkeypox virus: An emerging epidemic.

INTRODUCTION: A monkeypox outbreak is spreading in territories where the virus is not generally prevalent. The rapid and sudden emergence of monkeypox in numerous nations at the same time means that unreported transmission may have persisted. The number of reported cases is on a constant increase worldwide. At least 20 non-African countries, like Canada, Portugal, Spain, and the United Kingdom, have reported more than 57662 as of September 9th suspected or confirmed cases. This is the largest epidemic seen outside of Africa. Scientists are struggling to determine the responsible genes for the higher virulence and transmissibility of the virus. Because the viruses are related, several countries have begun acquiring smallpox vaccinations, which are believed to be very effective against monkeypox. METHODS: Bibliographic databases and web-search engines were used to retrieve studies that assessed monkeypox basic biology, life cycle, and transmission. Data were evaluated and used to explain the therapeutics that are under use or have potential. Finally, here is a comparison between how vaccines are being made now and how they were made in the past to stop the spread of new viruses. CONCLUSIONS: Available vaccines are believed to be effective if administered within four days of viral exposure, as the virus has a long incubation period. As the virus is zoonotic, there is still a great deal of concern about the viral genetic shift and the risk of spreading to humans. This review will discuss the virus's biology and how dangerous it is. It will also look at how it spreads, what vaccines and treatments are available, and what technologies could be used to make vaccines quickly using mRNA technologies.

Musashi-1-A Stemness RBP for Cancer Therapy?

The RNA-binding protein Musashi-1 (MSI1) promotes stemness during development and cancer. By controlling target mRNA turnover and translation, MSI1 is implicated in the regulation of cancer hallmarks such as cell cycle or Notch signaling. Thereby, the protein enhanced cancer growth and therapy resistance to standard regimes. Due to its specific expression pattern and diverse functions, MSI1 represents an interesting target for cancer therapy in the future. In this review we summarize previous findings on MSI1's implications in developmental processes of other organisms. We revisit MSI1's expression in a set of solid cancers, describe mechanistic details and implications in MSI1 associated cancer hallmark pathways and highlight current research in drug development identifying the first MSI1-directed inhibitors with anti-tumor activity.

Reshaping of the Arabidopsis thaliana Proteome Landscape and Co-regulation of Proteins in Development and Immunity.

Proteome remodeling is a fundamental adaptive response, and proteins in complexes and functionally related proteins are often co-expressed. Using a deep sampling strategy we define core proteomes of Arabidopsis thaliana tissues with around 10 000 proteins per tissue, and absolutely quantify (copy numbers per cell) nearly 16 000 proteins throughout the plant lifecycle. A proteome-wide survey of global post-translational modification revealed amino acid exchanges pointing to potential conservation of translational infidelity in eukaryotes. Correlation analysis of protein abundance uncovered potentially new tissue- and age-specific roles of entire signaling modules regulating transcription in photosynthesis, seed development, and senescence and abscission. Among others, the data suggest a potential function of RD26 and other NAC transcription factors in seed development related to desiccation tolerance as well as a possible function of cysteine-rich receptor-like kinases (CRKs) as ROS sensors in senescence. All of the components of ribosome biogenesis factor (RBF) complexes were found to be co-expressed in a tissue- and age-specific manner, indicating functional promiscuity in the assembly of these less-studied protein complexes in Arabidopsis.Furthermore, we characterized detailed proteome remodeling in basal immunity by treating Arabidopsis seeldings with flg22. Through simultaneously monitoring phytohormone and transcript changes upon flg22 treatment, we obtained strong evidence of suppression of jasmonate (JA) and JA-isoleucine (JA-Ile) levels by deconjugation and hydroxylation by IAA-ALA RESISTANT3 (IAR3) and JASMONATE-INDUCED OXYGENASE 2 (JOX2), respectively, under the control of JASMONATE INSENSITIVE 1 (MYC2), suggesting an unrecognized role of a new JA regulatory switch in pattern-triggered immunity. Taken together, the datasets generated in this study present extensive coverage of the Arabidopsis proteome in various biological scenarios, providing a rich resource available to the whole plant science community.

A multicomponent macrocyclization strategy to natural product-like cyclic lipopeptides: synthesis and anticancer evaluation of surfactin and mycosubtilin analogues.

A multicomponent macrocyclization strategy towards cyclic lipopeptides is described. The approach relies on the utilization of the Ugi and Passerini multicomponent reactions for the cyclization of peptides and oxo-peptides, and here it is employed for the construction of a small library of analogues of the natural products mycosubtilin and surfactin A. A key feature of this method is the simultaneous incorporation of either one or two exocyclic lipid tails along with the macrocyclic ring closure, which is only possible due to the multicomponent nature of the macrocyclization step. The evaluation of the anticancer activity of the lipopeptide library showed that the installation of a second lipid moiety in the surfactin scaffold leads to a more potent cytotoxicity in cancer cells. This is a new example of the multicomponent reaction potential in rapidly producing natural product analogues for biological screening.