Molecular authentication, metabolite profiling and in silico-in vitro cytotoxicity screening of endophytic Penicillium ramusculum from Withania somnifera for breast cancer therapeutics.

In the present study, we isolated a potent endophytic fungus from the roots of Withania somnifera. The endophytic fungal strain was authenticated as Penicillium ramusculum SVWS3 based on morphological and molecular sequencing using four gene data and phylogenetic analyses. In vitro cytotoxicity studies unveiled the remarkable cytotoxic potential of the crude extract derived from P. ramusculum, exhibiting dose-dependent effects on MDA-MB-468 and MCF-7 cells. At a concentration of 100 µg/mL, the crude extract resulted in cell viability of 29.78% for MDA-MB-468 cells and 14.61% for MCF-7 cells. The IC50 values were calculated as 62.83 ± 0.93 µg/mL and 17.23 ± 1.43 µg/mL, respectively for MDA-MB-468 and MCF-7 cells. Caspase activation assay established the underlying mechanism of the crude extract depicting the activation of caspases 3 and 7, indicating the induction of apoptosis in MCF-7 cells. Chemotaxonomic profiling elucidated the ability of P. ramusculum to synthesize a diverse array of bioactive compounds, including Fasoracetam, Tryprostatin B, Odorinol, Thyronine, Brevianamide F, Proglumide, Perlolyrine, Tyrphostin B48, Baptifoline, etc. Molecular docking studies inferred that Baptifoline, Brevianamide F, Odorinol, Perlolyrine, Thyronine, Tryphostin B48, and Tryprostatin B were the lead compounds that could effectively interact with the five selected target receptors of breast cancer, further surpassing the positive controls analyzed. Pharmacokinetic profiling revealed that Baptifoline, Odorinol, and Thyronine depicted an excellent therapeutic profile of druggability. These findings collectively substantiate the anticancer activity of bioactive metabolites synthesized by P. ramusculum SVWS3. Hence, the endophytic P. ramusculum SVWS3 can be an authentic source for developing novel chemotherapeutic drug formulations. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03906-3.

Determinants of durable humoral and T cell immunity in myeloma patients following COVID-19 vaccination.

OBJECTIVE: To describe determinants of persisting humoral and cellular immune response to the second COVID-19 vaccination among patients with myeloma. METHODS: This is a prospective, observational study utilising the RUDYstudy.org platform. Participants reported their second and third COVID-19 vaccination dates. Myeloma patients had an Anti-S antibody level sample taken at least 21 days after their second vaccination and a repeat sample before their third vaccination. RESULTS: 60 patients provided samples at least 3 weeks (median 57.5 days) after their second vaccination and before their third vaccination (median 176.0 days after second vaccine dose). Low Anti-S antibody levels (<50 IU/mL) doubled during this interval (p = .023) and, in the 47 participants with T-spot data, there was a 25% increase negative T-spot tests (p = .008). Low anti-S antibody levels prior to the third vaccination were predicted by lower Anti-S antibody level and negative T-spot status after the second vaccine. Independent determinants of a negative T-spot included increasing age, previous COVID infection, high CD4 count and lower percentage change in Anti-S antibody levels. CONCLUSIONS: Negative T-spot results predict low Anti-S antibody levels (<50 IU/mL) following a second COVID-19 vaccination and a number of biomarkers predict T cell responses in myeloma patients.

What do we know about the psychosocial issues associated with cancer during pregnancy? A scoping review and gap analysis.

OBJECTIVES: There is a global increase in the number of women diagnosed with cancer during their pregnancy and a nascent evidence base to guide their supportive care. The purposes of this study were to (1) map research on the psychosocial issues affecting women and their partners on diagnosis and treatment for cancer during pregnancy; (2) determine available supportive care or educational interventions; and (3) identify knowledge gaps for future research and development. DESIGN: Scoping review. SEARCH STRATEGY: Six databases were searched (Scopus, CINAHL, PsycINFO, Medline, Intermid, Maternal and Infant Health) to retrieve primary research (January 1995 to November 2021) investigating women and/or their partner's decision-making and their psychosocial outcomes during and after pregnancy. DATA EXTRACTION AND SYNTHESIS: Sociodemographic, gestational and disease characteristics of participants and psychosocial issues identified were extracted. Leventhal's self-regulatory model of illness provided a framework for mapping study findings enabling evidence synthesis and gap analysis. RESULTS: Twelve studies were included, conducted in eight countries in six continents. Most women (70% of 217) were diagnosed with breast cancer during pregnancy. Reporting of sociodemographic, psychiatric, obstetric and oncological characteristics that are important in assessing psychosocial outcomes was inconsistent. None of the studies had a longitudinal design and no supportive care or educational interventions were identified. The gap analysis highlighted the lack of evidence about pathways to diagnosis, impact of late effects and how internal/social resources may affect outcomes. CONCLUSIONS: Research has focused on women with gestational breast cancer. Little is known about those diagnosed with other cancers. We encourage future study designs to capture data on sociodemographic, obstetric, oncological and psychiatric characteristics and adopt a longitudinal approach to explore the longer term psychosocial impact on women and their families. Future research should include outcomes that are meaningful for women (and their partners) and draw on international collaboration to accelerate progress in this field.

Bacillus tequilensis PKDN31 and Bacillus licheniformis PKDL10 -As double headed swords to combat Fusarium oxysporum f. sp. lycopersici induced tomato wilt.

Wilt disease, caused by Fusarium oxysporum. f. sp. lycopersici, is a global threat to tomato production that needs to be addressed seriously. The current research envisages the use of two self-compatible Bacillus strains, Bacillus tequilensis PKDN31 and Bacillus licheniformis PKDL10, in a combinatorial approach. The spent supernatant of liquid cultures from strains PKDN31 and PKDL10 showed in vitro antifungal activity against Fusarium sp. attaining an inhibition percentage of 95.33% and 96.54%, respectively. The bacterial isolates lytic activity against Fusarium oxysporum was evaluated by scanning electron microscopic analysis and lytic enzyme production of amylase, lipase, protease and ß-1,3 glucanase. Furthermore, PKDN31 and PKDL10 produced siderophores and had root colonizing ability that enhanced the biocontrol efficiency. Combined in vivo inoculation of Bacillus tequilensis PKDN31 and Bacillus licheniformis PKDL10 on tomato seeds revealed that the strains could induce systemic resistance in tomato against Fusarium oxysporum. f. sp. lycopersici by increasing defence enzymes such as ß-1,3 glucanase, polyphenol oxidase, peroxidase, phenylalanine ammonia-lyase, chitinase, and total phenol accumulations. Pot culture experiments also proved the biocontrol efficacy of the above dual culture supplementation as this treatment displayed a better growth as well as defense against Fusarium challenge compared to the controls. The obtained results suggest that rhizobacterial isolates could be employed as systemic resistance inducers and biocontrol agents in tomato plants to protect against Fusarium wilt disease.

Immune response to COVID-19 vaccination is attenuated by poor disease control and antimyeloma therapy with vaccine driven divergent T-cell response.

Myeloma patients frequently respond poorly to bacterial and viral vaccination. A few studies have reported poor humoral immune responses in myeloma patients to COVID-19 vaccination. Using a prospective study of myeloma patients in the UK Rudy study cohort, we assessed humoral and interferon gamma release assay (IGRA) cellular immune responses to COVID-19 vaccination post second COVID-19 vaccine administration. We report data from 214 adults with myeloma (n = 204) or smouldering myeloma (n = 10) who provided blood samples at least three weeks after second vaccine dose. Positive Anti-spike antibody levels (> 50 iu/ml) were detected in 189/203 (92.7%), positive IGRA responses were seen in 97/158 (61.4%) myeloma patients. Only 10/158 (6.3%) patients were identified to have both a negative IGRA and negative anti-spike protein antibody response. In all, 95/158 (60.1%) patients produced positive results for both anti-spike protein serology and IGRA. After adjusting for disease severity and myeloma therapy, poor humoral immune response was predicted by male gender. Predictors of poor IGRA included anti-CD38/anti-BCMA (B-cell maturation antigen) therapy and Pfizer-BioNTech vaccination. Further work is required to understand the clinical significance of divergent cellular response to vaccination.

Prospective Assessment of Tumour Burden and Bone Disease in Plasma Cell Dyscrasias Using DW-MRI and Exploratory Bone Biomarkers.

Novel biomarkers for tumour burden and bone disease are required to guide clinical management of plasma cell dyscrasias. Recently, bone turnover markers (BTMs) and Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) have been explored, although their role in the prospective assessment of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) is unclear. Here, we conducted a pilot observational cohort feasibility study combining serum BTMs and DW-MRI in addition to standard clinical assessment. Fifty-five patients were recruited (14 MGUS, 15 smouldering MM, 14 new MM and 12 relapsed MM) and had DW-MRI and serum biomarkers (P1NP, CTX-1, ALP, DKK1, sclerostin, RANKL:OPG and BCMA) measured at baseline and 6-month follow-up. Serum sclerostin positively correlated with bone mineral density (r = 0.40-0.54). At baseline, serum BCMA correlated with serum paraprotein (r = 0.42) and serum DKK1 correlated with serum free light chains (r = 0.67); the longitudinal change in both biomarkers differed between International Myeloma Working Group (IMWG)-defined responders and non-responders. Myeloma Response Assessment and Diagnosis System (MY-RADS) scoring of serial DW-MRI correlated with conventional IMWG response criteria for measuring longitudinal changes in tumour burden. Overall, our pilot study suggests candidate radiological and serum biomarkers of tumour burden and bone loss in MM/MGUS, which warrant further exploration in larger cohorts to validate the findings and to better understand their clinical utility.