Role of IgG and IgM and proinflammatory non-specific markers in the diagnosis and prognosis of COVID-19 patients stratified by number of positive SARS-CoV-2 genes.

BACKGROUND: A prompt set of suitable biomarkers is needed in suspected COVID-19 patients. This study aims to assess patients positive for one or more gene associated with the C reactive protein (CRP) and procalcitonin (PCT) as non-specific pro-inflammatory markers and IgG and IgM kinetic as specific diagnostic and prognostic tools in SARS-CoV-2 RT-PCR positive patients. METHODS: We enrolled 101 patients within a two month time span (March 26th, 2020 to May 31st, 2020). A reverse transcription-Real-Time PCR assay on nasopharyngeal/oropharyngeal swabs was used for SARS-CoV-2 identification. Serum anti-SARS-CoV-2 IgM and IgG were measured by enzyme immunoassay, PCT levels by Enzyme linked fluorescent assay (ELFA)and CRP by nephelometry. RESULTS: We found that older patients were significantly associated with a worse prognosis. Serum IgM levels were significantly lower during the late stage of the disease, regardless of the presence of one or three genes and patients' outcome. On the contrary, IgG levels exhibited a higher concentration in the late phases of the illness, regardless of the gene found or patients' prognosis. With the exception of the very first sample tested, an increase in CRP in surviving patients (both one and three genes) and a time-dependent decrease of deceased patients CRP was found. PCT levels were always within the normal reference range. The difference between one gene and three genes patients was significant during late disease stages regarding IgG levels and also between three genes survivors versus three genes deceased, where the IgG levels were progressively increasing over time. CONCLUSIONS: The relevant finding of the present study is the significant and consistent increase of IgG and IgM in deceased patients. The associated evaluation of antibody kinetics and non specific inflammatory markers (CRP and PCT) in positive patients stratified according to the presence of one gene or three genes could help the clinician in both the diagnosis and prognosis of COVID-19 patients.

An Olive Leaf Extract Rich in Polyphenols Promotes Apoptosis in Cervical Cancer Cells by Upregulating p21Cip/WAF1 Gene Expression.

Most of the common drugs used to treat the cervical cancer, which main etiological factor is the HPV infection, cause side effects and intrinsic/acquired resistance to chemotherapy. In this study we investigated whether an olive leaf extract (OLE), rich in polyphenols, was able to exert anti-tumor effects in human cervical cancer cells (HeLa). MTT assay results showed a reduction of HeLa cells viability OLE-induced, concomitantly with a gene and protein down-regulation of Cyclin-D1 and an up-regulation of p21, triggering intrinsic apoptosis. OLE reduced NFkB nuclear translocation, which constitutive activation, stimulated by HPV-oncoproteins, promotes cancer progression and functional studies revealed that OLE activated p21Cip/WAF1 in a transcriptional-dependent-manner, by reducing the nuclear recruitment of NFkB on its responsive elements. Furthermore, OLE treatment counteracted epithelial-to-mesenchymal-transition and inhibited anchorage-dependent and -independent cell growth EGF-induced. Finally, MTT assay results revealed that OLE plus Cisplatin strengthened the reduction of cells viability Cisplatin-induced, as OLE inhibited NFkB, AkT and MAPK pathways, all involved in Cisplatin chemoresistance. In conclusion, we demonstrated that in HeLa cells OLE exerts pro-apoptotic effects, elucidating the molecular mechanism and that OLE could mitigate Cisplatin chemoresistance. Further studies are needed to explore the potential coadiuvant use of OLE for cervical cancer treatment.

NFKB1 promoter polymorphism: A new predictive marker of cytomegalovirus infection after kidney transplantation.

INTRODUCTION: Cytomegalovirus (CMV) infection represents a common cause of morbidity and mortality in kidney transplant recipients (KTR). The NF-kB signaling pathway is highly involved in the pathogenesis of CMV infection. The -94ins/delATTG functional polymorphism in the promoter of NFKB1 has been associated with low intracellular levels of the protein and high incidence of inflammatory and autoimmune disease. In this study, we evaluated the association of this NFKB1 polymorphism with the risk of CMV infection. METHODS: CMV infection was defined as virus isolation or detection of viral antigens or nucleic acid in any body fluid or tissue specimen. Using Cox regression and survival analysis, we analyzed the association between the polymorphism and CMV infection as well as recurrence in the first 12 months after transplantation. RESULTS: We analyzed the -94ins/delATTG NFKB1 polymorphism of 189 KTRs. The 65% of CMV infections occurred in ins/ins group. Survival free from CMV infection was 54.7% for ins/ins group and 79.4% for deletion carriers one year after transplantation (P < 0.0001). At multivariate regression, deletion carriers showed a lower risk of CMV infection and recurrence with respect to ins/ins KTRs (HR = 0.224 P = 0.0002; HR = 0.307, P = 0.012, respectively). CONCLUSIONS: In conclusion, pretransplantation screening for NFKB1 -94ins/delATTG polymorphism may predict CMV infection and improve the management of patients at higher risk of infection in the post-transplant period.

Testosterone in renal transplant patients: effect on body composition and clinical parameters.

BACKGROUND: Clinical studies have demonstrated that, after renal transplantation (TX), testosterone deficiency (TD) at the time of the procedure is independently associated with lower survival of the patient and graft. However, data between TD and the functional CAG polymorphism of the androgen receptor promoter (AR) are discordant. We investigated the prevalence of TD and its association with body composition, biochemical parameters, the Aging Males' Symptoms rating scale (AMS) domains and AR polymorphism. METHODS: In 112 TX patients, we assessed the AMS, biochemical/hormonal (FSH/LH/TT) anthropometric/bioimpedance analysis parameters, and AR CAG polymorphism of AR by gene sequencing. RESULTS: Median values of total testosterone (TT) were 340 ng/dl and 52% of TX patients were affected by TD. Significant correlations between TT and FSH and FSH and LH (p = 0.005, p < 0.0001, respectively) were found. TD patients had lower estimated glomerular filtration rate (eGFR) and hemoglobin (Hb) (p = 0.034, p = 0.022 respectively) and showed higher values of C-reactive protein (p = 0.023) and fat tissue index/adipose tissue mass (p = 0.034 and p = 0.021, respectively), and lower values of serum albumin (p = 0.003) and high-density lipoprotein-cholesterol (p = 0.038) levels. Significant differences were found in the number of patients on mammalian target of rapamycin inhibitors immunosuppressant therapy (p = 0.045). Logistic regression analysis did not show any correlation between age, AMS scores, TT or CAG repeat length, gonadotropins, time of the transplant, and dialysis. CONCLUSIONS: Our results suggest that in TX recipients an appropriate sexual hormonal evaluation should be performed, as we found a high prevalence of TD. However, further studies are needed to clarify the association between TD and patient and graft survival.