Nanobody-based pannexin1 channel inhibitors reduce inflammation in acute liver injury.

Background: The opening of pannexin1 channels is considered as a key event in inflammation. Pannexin1 channel-mediated release of adenosine triphosphate triggers inflammasome signaling and activation of immune cells. By doing so, pannexin1 channels play an important role in several inflammatory diseases.

Pannexin1 channels in the liver: an open enemy.

Pannexin1 proteins form communication channels at the cell plasma membrane surface, which allow the transfer of small molecules and ions between the intracellular compartment and extracellular environment. In this way, pannexin1 channels play an important role in various cellular processes and diseases. Indeed, a plethora of human pathologies is associated with the activation of pannexin1 channels.

An international multicentre propensity score matched analysis comparing between robotic versus laparoscopic left lateral sectionectomy.

Background: Left lateral sectionectomy (LLS) is one of the most commonly performed minimally invasive liver resections. While laparoscopic (L)-LLS is a well-established technique, over traditional open resection, it remains controversial if robotic (R)-LLS provides any advantages of L-LLS.

Methods: A post hoc analysis of 997 patients from 21 international centres undergoing L-LLS or R-LLS from 2006 to 2020 was conducted.

A scoring system for predicting malignancy in intraductal papillary mucinous neoplasms of the pancreas: a multicenter EUROPEAN validation.

Purpose: A preoperative estimate of the risk of malignancy for intraductal papillary mucinous neoplasms (IPMN) is important. The present study carries out an external validation of the Shin score in a European multicenter cohort.

Methods: An observational multicenter European study from 2010 to 2015.

Connexin-Based Channels in the Liver.

Connexin proteins oligomerize in hexameric structures called connexin hemichannels, which then dock to form gap junctions. Gap junctions direct cell-cell communication by allowing the exchange of small molecules and ions between neighboring cells. In this way, hepatic gap junctions support liver homeostasis.

Effects of Drugs Formerly Suggested for COVID-19 Repurposing on Pannexin1 Channels.

Although many efforts have been made to elucidate the pathogenesis of COVID-19, the underlying mechanisms are yet to be fully uncovered. However, it is known that a dysfunctional immune response and the accompanying uncontrollable inflammation lead to troublesome outcomes in COVID-19 patients. Pannexin1 channels are put forward as interesting drug targets for the treatment of COVID-19 due to their key role in inflammation and their link to other viral infections.

Effects of Drugs Formerly Proposed for COVID-19 Treatment on Connexin43 Hemichannels.

Connexin43 (Cx43) hemichannels form a pathway for cellular communication between the cell and its extracellular environment. Under pathological conditions, Cx43 hemichannels release adenosine triphosphate (ATP), which triggers inflammation. Over the past two years, azithromycin, chloroquine, dexamethasone, favipiravir, hydroxychloroquine, lopinavir, remdesivir, ribavirin, and ritonavir have been proposed as drugs for the treatment of the coronavirus disease 2019 (COVID-19), which is associated with prominent systemic inflammation.

An international multicenter propensity-score matched and coarsened-exact matched analysis comparing robotic versus laparoscopic partial liver resections of the anterolateral segments.

Background: Robotic liver resections (RLR) may have the ability to address some of the drawbacks of laparoscopic liver resections (LLR) but few studies have done a head-to-head comparison of the outcomes after anterolateral segment resections by the two techniques.

Methods: A retrospective study was conducted of 3202 patients who underwent minimally invasive LR of the anterolateral liver segments at 26 international centres from 2005 to 2020. Two thousand six hundred and six cases met study criteria of which there were 358 RLR and 1868 LLR cases.

Human and animal fertility studies in cystinosis reveal signs of obstructive azoospermia, an altered blood-testis barrier and a subtherapeutic effect of cysteamine in testis.

Cystinosis is an inherited metabolic disorder caused by autosomal recessive mutations in the CTNS gene leading to lysosomal cystine accumulation. The disease primarily affects the kidneys followed by extra-renal organ involvement later in life. Azoospermia is one of the unclarified complications which are not improved by cysteamine, which is the only available disease-modifying treatment.

Variations between the anatomical and functional distribution, based on 99 technetium -mebrofinate SPECT-CT scan, in patients at risk of post hepatectomy liver failure.

Background: The aim of the current study is to investigate the variations of anatomical (LV%) and functional remnant volumes (fLV%) and the dynamic uptake of Technetium-Mebrofinate (FRLF) measured from 99 Technetium-Mebrofinate SPECT-CT scan (TMSCT) in patients at high risk of post-hepatectomy liver failure (PHLF).

Methods: Variations in the measures of LV% and fLV% were assessed. The predictive accuracies of LV%, fLV% and FRLF with respect to PHLF were reported.

Fertility Preservation in Childhood Cancer: Endocrine Activity in Prepubertal Human Testis Xenografts Exposed to a Pubertal Hormone Environment.

Survivors of childhood cancer are at risk for long-term treatment-induced health sequelae, including gonadotoxicity and iatrogenic infertility. At present, for prepubertal boys there are no viable clinical options to preserve future reproductive potential. We investigated the effect of a pubertal induction regimen with gonadotrophins on prepubertal human testis xenograft development.

Testicular tissue cryopreservation is the preferred method to preserve spermatogonial stem cells prior to transplantation.

Research Question: Which cryopreservation method better protects reproductive potential: the cryopreservation of a testicular cell suspension (TCS) or the cryopreservation of testicular tissue (TET)?

Design: Two cryopreservation strategies for spermatogonial stem cells (SSCs) were compared in a mouse model: cryopreservation as TET or as TCS. Evaluated outcomes were number of viable cells after thawing, number and length of donor-derived colonies after spermatogonial stem cell transplantation (SSCT), number of litters, litter size and number of donor-derived pups after mating.

Results: Compared with cryopreserving TCS, cryopreservation of TET resulted in significantly higher numbers of viable cells after thawing (TET: 13.

Does co-transplantation of mesenchymal and spermatogonial stem cells improve reproductive efficiency and safety in mice?

Background: Spermatogonial stem cell transplantation (SSCT) is a promising therapy in restoring the fertility of childhood cancer survivors. However, the low efficiency of SSCT is a significant concern. SSCT could be improved by co-transplanting transforming growth factor beta 1 (TGFβ1)-induced mesenchymal stem cells (MSCs).

Population pharmacokinetics of primaquine and the effect of hepatic and renal dysfunction: An exploratory approach.

Objectives: We attempted to develop a population pharmacokinetic model for primaquine (PQ) and evaluate the effect of renal and hepatic dysfunction on PQ pharmacokinetics.

Materials And Methods: The data were collected from a prospective, nonrandomized clinical study in healthy volunteers and patients with mild-moderate hepatic dysfunction and renal dysfunction. Model development was conducted using NONMEM software, and parameter estimation was conducted using first-order conditional estimation with interaction method.

Effect of recombinant human vascular endothelial growth factor on testis tissue xenotransplants from prepubertal boys: a three-case study.

Research Question: Does recombinant human vascular endothelial growth factor (VEGF-165) improve the efficiency of human immature testis tissue (ITT) xenotransplantation?

Design: ITT fragments from three prepubertal boys were cultured for 5 days with VEGF-165 or without (control) before xenotransplantation into the testes of immunodeficient mice. Xenotransplants were recovered at 4 and 9 months post-transplantation and vascularization, seminiferous tubule integrity, number of spermatogonia and germ cell differentiation were evaluated by histology and immunohistochemistry.

Results: Transplants from donor 1 and donor 2 treated with VEGF demonstrated higher vascular surface (P = 0.

Co-transplantation of mesenchymal stem cells improves spermatogonial stem cell transplantation efficiency in mice.

Background: Spermatogonial stem cell transplantation (SSCT) could become a fertility restoration tool for childhood cancer survivors. However, since in mice, the colonization efficiency of transplanted spermatogonial stem cells (SSCs) is only 12%, the efficiency of the procedure needs to be improved before clinical implementation is possible. Co-transplantation of mesenchymal stem cells (MSCs) might increase colonization efficiency of SSCs by restoring the SSC niche after gonadotoxic treatment.

What is the best protocol to cryopreserve immature mouse testicular cell suspensions?

Research Question: From a clinical perspective, which parameters grant optimal cryopreservation of mouse testicular cell suspensions?

Design: We studied the effect of different cryopreservation rates, the addition of sugars, different vessels and the addition of an apoptotic inhibitor on the efficiency of testicular cell suspension cryopreservation. After thawing and warming, testicular cell suspensions were transplanted to recipient mice for further functional assay. After selecting the optimal cryopreservation procedure, a second experiment compared the transplantation efficiency between the selected freezing protocol and fresh testicular cell suspensions.

Evaluation of pharmacokinetics of single-dose chloroquine in malnourished children with malaria- a comparative study with normally nourished children.

Objectives: Studies on antimalarial kinetics in children or adults who are undernourished or malnourished are both limited and have yielded conflicting results. The present study was carried out with the objectives of evaluating the pharmacokinetics of single dose chloroquine and its metabolite desethylchloroquine in children who were undernourished and compare them with children who were normally nourished.

Methods: Children of either gender between the ages of 5 and 12 years, smear positive for malaria and classified either as well nourished or undernourished were included.

Safety and Efficacy of Growth Factor Concentrate in the Treatment of Nasolabial Fold Correction: Split Face Pilot Study.

Background: Growth factors have long been known as an effective treatment for facial wrinkles. We developed growth factor concentrate (GFC) from the platelets and evaluated their clinical outcome in nasolabial folds.

Aims And Objectives: We evaluated safety and efficacy of autologous GFC on patients with nasolabial folds.

Differential proteomic profile of spermatogenic and Sertoli cells from peri-pubertal testes of three different bovine breeds.

Sub-fertility is one of the most common problems observed in crossbred males, but the etiology remains unknown in most of the cases. Although proteomic differences in the spermatozoa and seminal plasma between breeds have been investigated, the possible differences at the sperm precursor cells and supporting/nourishing cells have not been studied. The present study reports the differential proteomic profile of spermatogenic and Sertoli cells in crossbred and purebred bulls.

Evaluation of cytochrome P450 2D6 phenotyping in healthy adult Western Indians.

Background: Cytochrome P450 2D6 (CYP2D6) metabolizes around 25% of the drugs used in therapeutics and different polymorphisms have been identified in various populations. This study aimed at finding the prevalence of CYP2D6 polymorphisms using dextromethorphan as a probe drug.

Materials And Methods: Healthy participants were administered 60 mg dextromethorphan after an overnight fast and 5 ml of blood was collected 3 h postdose.