Comparing advanced platforms for local excision of rectal lesions.

Background: Transanal surgery facilitates organ preservation in select patients with benign and early malignant rectal lesions to avoid the functional consequences of radical surgery. The transanal endoscopic microsurgery (TEM) platform created a standard for local excision with lower margin positivity and recurrence rates than traditional transanal excision. The single-port robot (SP r) presents a promising alternative transanal platform.

Perioperative outcomes for single-port robotic versus single-incision laparoscopic surgery: a comparative analysis in colorectal cancer surgery.

Background: Single-incision laparoscopic surgery (SILS) may offer improved cosmesis, reduced postoperative pain and faster recovery than conventional platforms, but widespread implementation was limited by technical demands. A single-port robotic platform was recently introduced, with components that further enhance SILS benefits without the technical challenges. No study to date has compared the two platforms to validate benefits.

Longitudinal Analysis of Local Recurrence and Survival After Transanal Abdominal Transanal Radical Proctosigmoidectomy for Low Rectal Cancer Treated With Neoadjuvant Chemoradiation Therapy.

Background: The transanal abdominal transanal radical proctosigmoidectomy was developed in 1984 as a sphincter preservation surgery in patients with low rectal cancers after preoperative radiation therapy. While serving as a catalyst for disruptive sphincter preservation surgery, it continues to be used and evolve. With the controversy over safety and local recurrence in other sphincter-preserving surgery, review of transanal abdominal transanal radical proctosigmoidectomy long-term oncologic outcomes is warranted.

SUGT1 controls susceptibility to HIV-1 infection by stabilizing microtubule plus-ends.

Understanding the viral-host cell interface during HIV-1 infection is a prerequisite for the development of innovative antiviral therapies. Here we show that the suppressor of G2 allele of skp1 (SUGT1) is a permissive factor for human immunodeficiency virus (HIV)-1 infection. Expression of SUGT1 increases in infected cells on human brain sections and in permissive host cells.

HIV-1 Envelope Overcomes NLRP3-Mediated Inhibition of F-Actin Polymerization for Viral Entry.

Purinergic receptors and nucleotide-binding domain leucine-rich repeat containing (NLR) proteins have been shown to control viral infection. Here, we show that the NLR family member NLRP3 and the purinergic receptor P2Y2 constitutively interact and regulate susceptibility to HIV-1 infection. We found that NLRP3 acts as an inhibitory factor of viral entry that represses F-actin remodeling.

Erratum to 'HMGB1/anti-HMGB1 antibodies define a molecular signature of early stages of HIV-Associated Neurocognitive Disorders (HAND)'.

[This corrects the article DOI: 10.1016/j.heliyon.

HMGB1/anti-HMGB1 antibodies define a molecular signature of early stages of HIV-Associated Neurocognitive Isorders (HAND).

Background: HIV-associated neurocognitive disorders (HAND) persist in the post-HAART era, characterized by asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorders (MND). High mobility group box 1 (HMGB1) is a non-histone chromosomal protein widely expressed in the nucleus of all eukaryotic cells, including brain cells, which acts as a potent proinflammatory cytokine when actively secreted from immune cells. Recent reports suggested that HMGB1 acts on microglial cells to promote neuroinflammation.

Superior Efficacy of a Human Immunodeficiency Virus Vaccine Combined with Antiretroviral Prevention in Simian-Human Immunodeficiency Virus-Challenged Nonhuman Primates.

Unlabelled: Although vaccines and antiretroviral (ARV) prevention have demonstrated partial success against human immunodeficiency virus (HIV) infection in clinical trials, their combined introduction could provide more potent protection. Furthermore, combination approaches could ameliorate the potential increased risk of infection following vaccination in the absence of protective immunity. We used a nonhuman primate model to determine potential interactions of combining a partially effective ARV microbicide with an envelope-based vaccine.

HMGB1 Is Involved in IFN-α Production and TRAIL Expression by HIV-1-Exposed Plasmacytoid Dendritic Cells: Impact of the Crosstalk with NK Cells.

Plasmacytoid dendritic cells (pDCs) are innate sensors of viral infections and important mediators of antiviral innate immunity through their ability to produce large amounts of IFN-α. Moreover, Toll-like receptor 7 (TLR7) and 9 (TLR9) ligands, such as HIV and CpG respectively, turn pDCs into TRAIL-expressing killer pDCs able to lyse HIV-infected CD4+ T cells. NK cells can regulate antiviral immunity by modulating pDC functions, and pDC production of IFN-α as well as cell-cell contact is required to promote NK cell functions.

Understanding factors that modulate HIV infection at the female genital tract mucosae for the rationale design of microbicides.

Women are now becoming the pivot of the epidemiological spread of HIV infection worldwide, especially in developing countries. Therefore, research to develop an efficient microbicide is now a priority for the prevention of HIV-1 acquisition in exposed women. However, recent disappointing failures in microbicide clinical trials revealed major gaps in basic and applied knowledge that hinder the development of effective microbicide formulations.

Single-stranded DNA oligonucleotides inhibit TLR3-mediated responses in human monocyte-derived dendritic cells and in vivo in cynomolgus macaques.

TLR3 is a key receptor for recognition of double-stranded RNA and initiation of immune responses against viral infections. However, hyperactive responses can have adverse effects, such as virus-induced asthma. Strategies to prevent TLR3-mediated pathology are therefore desired.

Partial inactivation of CCR5- and CXCR4- tropic HIV-1 by human urine.

Human urine has been poorly investigated with regard to infection with human immunodeficiency virus (HIV). Here, we have studied the anti-infective functional properties of human urine against HIV. The effect of fresh urine pools on CCR5- and CXCR4-tropic HIV-1 was evaluated by using four in vitro mucosal models: reduction of infectivity of urine-treated HIV-1 particles, HIV-1 attachment to immature monocyte-derived dendritic cells (iMDDC), transfer of HIV-1 particles from iMDDC to autologous CD4 T cells, and HIV-1 transcytosis through epithelial cells.

Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection.

Extracellular adenosine triphosphate (ATP) can activate purinergic receptors of the plasma membrane and modulate multiple cellular functions. We report that ATP is released from HIV-1 target cells through pannexin-1 channels upon interaction between the HIV-1 envelope protein and specific target cell receptors. Extracellular ATP then acts on purinergic receptors, including P2Y2, to activate proline-rich tyrosine kinase 2 (Pyk2) kinase and transient plasma membrane depolarization, which in turn stimulate fusion between Env-expressing membranes and membranes containing CD4 plus appropriate chemokine co-receptors.

Combinatorial prevention of HIV transmission in women: the case for a vaginal microbicide.

Women are now becoming pivotal in the epidemiological spread of HIV infection throughout the world, especially in developing countries, where heterosexual transmission accounts for more than 80% of all new HIV infections. Recently, significant but partial successes have occurred in the field of HIV prevention, including male circumcision, preventive HIV vaccines, vaginal microbicides and oral pre-exposure prophylaxis, and there is increasingly widespread access to antiretroviral treatment. However, none of the currently available tools for HIV intervention are sufficiently effective, particularly for women, and all require further development.

Differential activity of candidate microbicides against early steps of HIV-1 infection upon complement virus opsonization.

Background: HIV-1 in genital secretions may be opsonized by several molecules including complement components. Opsonized HIV-1 by complement enhances the infection of various mucosal target cells, such as dendritic cells (DC) and epithelial cells.

Results: We herein evaluated the effect of HIV-1 complement opsonization on microbicide candidates' activity, by using three in vitro mucosal models: CCR5-tropic HIV-1JR-CSF transcytosis through epithelial cells, HIV-1JR-CSF attachment on immature monocyte-derived dendritic cells (iMDDC), and infectivity of iMDDC by CCR5-tropic HIV-1BaL and CXCR4-tropic HIV-1NDK.

Potent in vitro inactivation of both free and cell-associated CCR5- and CXCR4-tropic HIV-1 by common commercial soap bars from South Africa.

We showed herein the potent virucidal effect of soap and water solutions against both CCR5-tropic and CXCR4-tropic cell-free HIV-1 strains, and cytotoxicity for HIV-1-infected lymphocytes during short incubation durations, ranging from 30 seconds to 2 minutes. These observations indicate a rapid inhibitory effect of soap and water on viral infectivity.

Escape of HIV-1-infected dendritic cells from TRAIL-mediated NK cell cytotoxicity during NK-DC cross-talk--a pivotal role of HMGB1.

Early stages of Human Immunodeficiency Virus-1 (HIV-1) infection are associated with local recruitment and activation of important effectors of innate immunity, i.e. natural killer (NK) cells and dendritic cells (DCs).

In vitro synergistic activity against CCR5-tropic HIV-1 with combinations of potential candidate microbicide molecules HHA, KRV2110 and enfuvirtide (T20).

Objectives: To block the different mechanisms of HIV mucosal transmission, it is likely that use of several microbicide molecules will lead to the best protection against HIV transmission. Indeed, the combination of microbicides with complementary mechanisms of action is expected to increase the antiviral potency of the formulation.

Methods: The gp120-interacting plant lectin HHA ('Hippeastrum hybrid agglutinin'), the non-nucleoside reverse transcriptase inhibitor KRV2110 and the fusion inhibitor enfuvirtide (T20) were combined in 12 drug associations by using the Ray combination design method.

Differential modulation of CCR5-tropic human immunodeficiency virus-1 transfer from macrophages towards T cells under interleukin-4/interleukin-13 microenvironment.

Macrophages constitute major human immunodeficiency virus type 1 (HIV-1) reservoirs at the mucosal level, and their functional activity is modulated by cytokine environments that could play a role in HIV-1 mucosal spread. As proof of concept, we herein evaluated the modulation of HIV/macrophages interactions associated with two ubiquitous T(h)2 cytokines, namely, interleukin (IL)-4 and IL-13, using the in vitro model of R5-HIV-1 transfer from macrophages to T lymphocytes. Monocyte-derived macrophages differentiated in the presence of IL-4 (M-4) transferred the virus to T cells more efficiently than those differentiated in the presence of interleukin-13 (M-13), likely because to their high capacity to capture and produce HIV-1 and to recruit HIV-1 target T cell.

Apical interactions of HIV type 1 with polarized HEC-1 cell monolayer modulate R5-HIV type 1 spread by submucosal macrophages.

The in vitro model of HIV-1 transcytosis through a monolayer of HEC-1 cells is thought to mimic the mucosal crossing of the virus that may occur in vivo. We evaluated whether the stimulation of HEC-1 by HIV may modulate HIV infection of macrophages. Thus, the ability to capture, produce, and transfer R5 viruses to T cells, attract T cells, and finally produce cytokines/chemokines, was compared between untreated macrophages (M0) and macrophages differentiated in the presence of medium collected at the basolateral pole of HEC-1, which were unstimulated [M(BL)] or stimulated with either R5-HIV-1Ba-L [M(BL-R5)] or X4-HIV-1NDK [M(BL-X4)].

Microbicides: an emerging science of HIV-1 prevention in women-15th Conference on Retroviruses and Opportunistic Infections, Boston, USA, 3-6 February 2008.

Women account for almost 60% of human immunodeficiency virus type 1 (HIV-1) infections in Sub-Saharan Africa. HIV-1 prevention tools such as condoms, abstinence and monogamy are not always feasible options for women due to various socio-economic and cultural factors. Microbicides are anti-microbial medications formulated for topical administration to prevent the sexual transmission of HIV-1 and other pathogens.

HMGB1-dependent triggering of HIV-1 replication and persistence in dendritic cells as a consequence of NK-DC cross-talk.

Background: HIV-1 has evolved ways to exploit DCs, thereby facilitating viral dissemination and allowing evasion of antiviral immunity. Recently, the fate of DCs has been found to be extremely dependent on the interaction with autologous NK cells, but the mechanisms by which NK-DC interaction controls viral infections remain unclear. Here, we investigate the impact of NK-DC cross-talk on maturation and functions of HIV-infected immature DCs.

Analysis of apoptotic pathways by multiparametric flow cytometry: application to HIV infection.

Flow cytometry analysis of apoptosis allows the detection, at the single cell level, of essential features of apoptotic cells. They include alterations in plasma membrane integrity, detected with the 7-aminoactinomycin D assay, translocation of phosphatidylserine from the inner to the outer layer of the plasma membrane analyzed with the annexin-V/PI assay, DNA strand breaks in apoptotic nuclei measured with the in situ nick translation and terminal deoxynucleotidyl transferase dUTP-mediated nick end labeling assays, and morphological modifications evidenced with FSC/SSC criteria. In addition, mitochondrial events such as the drop in transmembrane potential DeltaPsi(m) can be detected with the cationic lipophilic dye 3,3'-dihexyloxacarbocyanine iodide and downregulation of the Bcl-2 molecule by specific intracellular staining.

Pre-clinical development as microbicide of zinc tetra-ascorbo-camphorate, a novel terpenoid derivative: potent in vitro inhibitory activity against both R5- and X4-tropic HIV-1 strains without significant in vivo mucosal toxicity.

Background: Terpenoid derivatives originating from many plants species, are interesting compounds with numerous biological effects, such as anti-HIV-1 activity. The zinc tetra-ascorbo-camphorate complex (or "C14"), a new monoterpenoid derivative was evaluated in vitro for its anti-HIV-1 activity on both R5- and X4-HIV-1 infection of primary target cells (macrophages, dendritic cells and T cells) and on HIV-1 transfer from dendritic cells to T cells.

Results: The toxicity study was carried out in vitro and also with the New Zealand White rabbit vaginal irritation model.