Leishmania donovani and HIV co-infection in vitro: Identification and characterization of main molecular players.

The incidence of Leishmania/HIV co-infection is growing and few studies detail the cellular processes and macromolecules participating in co-infection. Thus, the goal of this study was to partially describe the Leishmania/HIV co-infection events by measuring molecular and functional parameters associated with both pathogens in vitro. MT-4 cells (human T-lymphocytes), primary monocytes, and peripheral blood mononuclear cells were exposed to HIV and/or Leishmania donovani. The cytopathic effects generated by the pathogens were observed through microscopy. Viral replication was assessed by monitoring p24 protein levels and parasitic proliferation/infectivity was determined using Giemsa staining. Changes in molecular markers were evaluated by ELISA and fluorescence assays. Our results showed that our system reassembles the main parameters previously described for Leishmania/HIV co-infection in patients in terms of potentiation of parasitic and viral replication/infectivity, amplification of syncytia induction, and alterations of cell viability. In addition, an amplification in NF-κB activation, changes in CXCR4/CCR5 surface expression, and a Th1→Th2 variation in cytokine/chemokine secretion were demonstrated. Altogether, this study could contribute to gain a deep understanding of the molecular events associated with Leishmania/HIV co-infection.

SARS-CoV-2 host tropism: An in silico analysis of the main cellular factors.

Recent reports have shown that small and big felines could be infected by SARS-CoV-2, while other animals, like swines and mice, are apparently not susceptible to this infection. These findings raise the question of the role of cell factors associated with early stages of the viral infection in host selectivity. The cellular receptor for SARS-CoV-2 is the Angiotensin Converting Enzyme (ACE2). Transmembrane protease serine 2 (TMPRSS2) has been shown to prime the viral spike for its interaction with its receptor. GRP78 has also been proposed as a possible co-receptor. In this study, we used several bioinformatics approaches to bring clues in the interaction of ACE2, TMPRSS2, and GRP78 with SARS-CoV-2. We selected several mammalian hosts that could play a key role in viral spread by acting as secondary hosts (cats, dogs, pigs, mice, and ferrets) and evaluated their predicted permissiveness by in silico analysis. Results showed that ionic pairs (salt bridges, N-O pair, and long-range interactions) produced between ACE2 and the viral spike has an essential function in the host interaction. On the other hand, TMPRSS2 and GRP78 are proteins with high homology in all the evaluated hosts. Thus, these proteins do not seem to play a role in host selectivity, suggesting that other factors may play a role in the non-permissivity in some of these hosts. These proteins represent however interesting cell targets that could be explored in order to control the virus replication in humans and in the intermediary hosts.

Histological alterations in Leydig cells and macrophages in azoospermic men.

The study aimed to compare the histological features of Leydig cells and macrophages in the testicular interstitium of obstructive versus nonobstructive azoospermia. Thirty-nine azoospermic men undergoing testicular sperm extraction during intracytoplasmic sperm injection were allocated into obstructive azoospermia group (GI) and nonobstructive azoospermia group (GII) which was subdivided into Sertoli cell-only syndrome (GIIA), germ cell arrest (GIIB) and hypospermatogenesis (GIIC) subgroups. Serum LH, FSH and testosterone levels were measured. Ultrastructural changes and the mean number of CD68-positive cells were estimated in the different groups. In GIIA, Leydig cells' processes came in contact with macrophages and showed smooth endoplasmic reticulum dilatation. In GIIB, Leydig cells showed apoptotic changes. Macrophages were commonly encountered in their vicinity demonstrating large number of lysosomes. In GIIC, Leydig cells showed euchromatic nuclei. Macrophages showed expulsion of their lysosomal contents in the interstitium surrounded by apoptotic bodies. The mean count of total CD68-positive macrophages was higher in cases of obstructive azoospermia with nonsignificant differences compared to nonobstructive azoospermia groups. Significant increase in FSH level was detected in GIIA compared to GI. It is concluded that structural interactions might take place between Leydig cells and macrophages in the interstitial tissue of azoospermic men.

Oxidative Stress -a Phenotypic Hallmark of Fanconi Anemia and Down Syndrome: The Effect of Antioxidants.

BACKGROUND: Oxidative stress plays a major role in the pathogenesis of leukemia-prone diseases such as Fanconi anemia (FA) and Down syndrome (DS). AIM: To explore the oxidative stress state in children with DS and FA by estimating the levels of antioxidants (e.g., malondialdehyde [MDA], total antioxidant capacity, and superoxide dismutase [SOD] activity) and DNA damage, and to evaluate of the effect of antioxidant treatment on these patients. SUBJECTS AND METHODS: The study included 32 children clinically diagnosed with (15 patients) and FA (17 patients) in addition to 17 controls matched for age and sex. MDA, total antioxidant capacity, SOD activity, and DNA damage were measured. Antioxidants including Vitamin A, E, and C were given to the patients according to the recommended daily allowance for 6 months. Clinical follow-up and re-evaluation were conducted for all patients. Laboratory tests including complete blood count, karyotyping, DNA damage, and oxidative stress were re-evaluated. Statistical analysis was performed using statistical computer program Statistical Package for the Social Sciences version 14.0. RESULTS: Children with FA and DS had elevated levels of oxidative stress and more DNA damage than controls. Oxidative stress parameters and DNA damage improved in FA and DS patients after antioxidant administration. CONCLUSION: Early administration of antioxidants to FA and DS patients is recommended for slowing of the disease course with symptoms amelioration and improvement of general health.