Exploring vasculogenesis in the normal human kidney and clear cell renal cell carcinoma: insights from development to tumor progression and biomarkers for therapy response.

Vasculogenesis, which refers to the development of blood vessels from precursor cells, is a process that occurs predominantly during early embryonic life. It plays a crucial role in the establishment of the primitive vascular network. Vasculogenesis diminishes throughout the fetal vascular remodeling process, giving way to angiogenesis, which becomes the predominant mechanism after birth. At first, the development of the kidney's blood vessels depends on vasculogenesis, and then both vasculogenesis and angiogenesis happen simultaneously. Both processes are necessary for the normal development of the renal vasculature. Although the kidneys are highly vascularized, our understanding of normal kidney vasculogenesis is still incomplete. This lack of knowledge may explain the limited data available on the role of vasculogenesis in the progression and spread of renal cancers. In other types of cancer, researchers have well documented the phenomenon of tumor vasculogenesis. However, there is currently limited and fragmented information about the occurrence of clear-cell renal cell carcinomas (cc-RCC). In this article, we provide a comprehensive review of the current understanding of normal kidney vasculogenesis and vasculogenic pathways in clear cell renal cell carcinoma (cc-RCC). We specifically focus on cellular precursors, growth factors, and the influence of the normal and tumor environments on these processes. It will carefully look at how tumor vasculogenesis might affect the growth and metastasis of clear cell renal cell carcinoma (cc-RCC), as well as how it might affect the effectiveness of drugs and the development of therapy resistance.

Reassessing Breast Cancer-Associated Fibroblasts (CAFs) Interactions with Other Stromal Components and Clinico-Pathologic Parameters by Using Immunohistochemistry and Digital Image Analysis (DIA).

BACKGROUND: Breast cancer (BC) stroma has CD34- and αSMA-positive cancer-associated fibroblasts (CAFs) differently distributed. During malignant transformation, CD34-positive fibroblasts decrease while αSMA-positive CAFs increase. The prevalence of αSMA-positive CAFs in BC stroma makes microscopic examination difficult without digital image analysis processing (DIA). DIA was used to compare CD34- and αSMA-positive CAFs among breast cancer molecular subgroups. DIA-derived data were linked to age, survival, tumor stroma vessels, tertiary lymphoid structures (TLS), invasion, and recurrence. METHODS: Double immunostaining for CD34 and αSMA showed different CAF distribution patterns in normal and BC tissues. Single CD34 immunohistochemistry on supplemental slides quantified tumor stroma CD34_CAFs. Digital image analysis (DIA) data on CAF density, intensity, stromal score, and H-score were correlated with clinico-pathologic factors. RESULTS: CD34/αSMA CAF proportion was significantly related to age in Luminal A (LA), Luminal B (LB), and HER2 subtypes. CD34_CAF influence on survival, invasion, and recurrence of LA, LB-HER2, and TNBC subtypes was found to be significant. The CD34/αSMA-expressing CAFs exhibited a heterogeneous impact on stromal vasculature and TLS. CONCLUSION: BC stromal CD34_CAFs/αSMA_CAFs have an impact on survival, invasion, and recurrence differently between BC molecular subtypes. The tumor stroma DIA assessment may have predictive potential to prognosis and long-term follow-up of patients with breast cancer.

Histological and immunohistochemical outcomes after microdissection TESE in contrast with hormonal profile, testis volume and genetics in patients with azoospermia.

A limited number of individuals with non-obstructive azoospermia (NOA) may recover spermatozoa through traditional testicular sperm extraction (TESE) techniques. There is an ongoing debate over the effectiveness of microdissection TESE compared to standard TESE methods. Microdissection TESE (micro-TESE) techniques enable the identification of spermatogenesis foci in non-obstructive forms of azoospermia. Only histological examination can provide an objective and definitive assessment of the testicular phenotype. This study aimed to evaluate the correlation between histopathological findings after microdissection TESE (micro-TESE) and the predictive role of various factors in determining the success of sperm retrieval. We evaluated 24 patients with azoospermia who underwent micro-TESE and considered the patient's hormonal profile, testis ultrasound, genetic evaluation, histology, and immunohistology (PLAP antibody) of collected testis biopsies. The preoperative blood FSH level, in conjunction with other parameters, may aid in the prediction of micro-TESE success. Sensitivity increases, and specificity decreases with higher FSH levels. Furthermore, testicular volume and FSH levels are typically normal in patients with maturation arrest. In conclusion, hormones, ultrasound evaluation of the testicles, testis volume, and available genetic tests have a predictive value in differentiating obstructive azoospermia (OA) from NOA with various sensitivity and specificity rates. Histological and immunohistochemical evaluation establishes the testicular phenotype accurately and guides patient management.

Characterisation of the Antibody Response in Sinopharm (BBIBP-CorV) Recipients and COVID-19 Convalescent Sera from the Republic of Moldova.

The early availability of effective vaccines against SARS-CoV-2, the aetiologic cause of COVID-19, has been at the cornerstone of the global recovery from the pandemic. This study aimed to assess the antispike RBD IgG antibody titres and neutralisation potential of COVID-19 convalescent plasma and the sera of Moldovan adults vaccinated with the Sinopharm BBIBP-CorV vaccine. An IgG ELISA with recombinant SARS-CoV-2 spike RBD and two pseudovirus-based neutralisation assays have been developed to evaluate neutralising antibodies against SARS-CoV-2 in biosafety level 2 containment facilities. A significant moderate correlation was observed between IgG titres and the overall neutralising levels for each neutralisation assay (ρ = 0.64, p < 0.001; ρ = 0.52, p < 0.001). A separate analysis of convalescent and vaccinated individuals showed a higher correlation of neutralising and IgG titres in convalescent individuals (ρ = 0.68, p < 0.001, ρ = 0.45, p < 0.001) compared with vaccinated individuals (ρ = 0.58, p < 0.001; ρ = 0.53, p < 0.001). It can be concluded that individuals who recovered from infection developed higher levels of antispike RBD IgG antibodies. In comparison, the Sinopharm-vaccinated individuals produced higher levels of neutralising antibodies than convalescent plasma.

Introducing N-Heteroaromatic Bases into Copper(II) Thiosemicarbazon Complexes: A Way to Change their Biological Activity.

Three new copper(II) complexes, [Cu(1,10-Phen)(L)] (1), [Cu(2,2'-Bpy)(L)] (2) and [Cu(3,4-Lut)(L)] (3), where H2 L=2-[(2,4-dihydroxyphenyl)methylidene]-N-(prop-2-en-1-yl)hydrazine-1-carbothioamide, 1,10-Phen=1,10-phenanthroline, 2,2'-Bpy=2,2'-bipyridine, 3,4-Lut=3,4-lutidine, have been synthesized and characterized by elemental analysis, FTIR spectroscopy and single crystal X-ray crystallography (1, 2). All compounds are mononuclear. The introduction of a monodentate N-heteroaromatic base (3,4-dimethylpyridine) has led to a significant increase of antimicrobial activity against Gram-negative Escherichia coli and antifungal activity against Candida albicans compared to the pro-ligand and the precursor complex [Cu(L)H2 O]. The introduction of bidentate N-heteroaromatic bases did not lead to such increase of antimicrobial and antifungal activities. Moreover, complex 3 surpasses the inhibitory activity of tetracycline toward Enterobacter cloacae and the inhibitory activity of fluconazole toward Candida parapsilosis and Cryptococcus neoformans. The study of antioxidant activity against cation radicals ABTS⋅+ showed that complexes 1-3 are more active than Trolox, but only introduction of the monodentate N-heteroaromatic base (3,4-dimethylpyridine) led to the increase of antioxidant properties compared to the precursor complex.

The Correlations of Clinical and Biochemical Indices of Vitamin D with Erectile Dysfunction.

Erectile dysfunction is a multifactorial disease; it has been demonstrated that endothelial dysfunction plays an essential role in the pathogenesis of this disease, and Vitamin D deficiency is considered to favor endothelial lesions. Our study, based on a group of 58 patients who have erectile dysfunction and a control group of 26 healthy subjects, tends to confirm that low levels of vitamin D could potentiate the severity of erectile dysfunction, promoting endothelial dysfunction. Statistical analysis using the Pearson's correlation criteria showed a robust and significant correlation between vitamin D levels and erectile dysfunction severity (ρ=0.752, p<0.000) according to the SHIM (Sexual Health Inventory For Men) questionnaire. Also, in patients with erectile dysfunction, there is a strong association between vitamin D and testosterone levels (ρ=0.728, p<0.000). At the same time, a negative correlation between vitamin D and BMI (ρ=-0.517, p<0.000); cholesterol (ρ=-0.560, p<0.001), and triglycerides(ρ=-0.529, p<0.005) was observed. Also, a moderate correlation between erectile dysfunction severity degree and testosterone levels (ρ=0.544) was also detected, and the same severity parameter of erectile dysfunction correlates negatively with cholesterol levels (ρ=-0.534). In its turn, the testosterone level correlates negatively with other biochemical indices: cholesterol (ρ=-0.694) and triglycerides (ρ=-0.670). Vitamin D level reduction, concomitantly with decreased testosterone and increased cholesterol, contributes to the development and maintenance of erectile dysfunction, more probably through endothelial mechanisms. The assessment of vitamin D values can be used as an independent marker in erectile dysfunction assessment. Thus, one of the diagnostic tests recommended for erectile dysfunction should be the determination of the vitamin D serum level.