Characterization of the Abracl-Expressing Cell Populations in the Embryonic Mammalian Telencephalon.

Abracl (ABRA C-terminal-like protein) is a small, non-typical winged-helix protein that shares similarity with the C-terminal domain of the protein ABRA (Actin-Binding Rho-Activating protein). The role of Abracl in the cell remains elusive, although in cancer cells, it has been implicated in proliferation, migration and actin dynamics. Our previous study showed that Abracl mRNA was expressed in the dividing cells of the subpallial subventricular zone (SVZ), in the developing cortical plate (CP), and in the diencephalic SVZ; however, the molecular identities of the Abracl-expressing cell populations were not defined in that work. In this study, we use double immunofluorescence to characterize the expression of Abracl on sections of embryonic murine (E11.5-E18.5) and feline (E30/31-E33/34) telencephalon; to this end, we use a battery of well-known molecular markers of cycling (Ki67, Ascl1, Dlx2) or post-mitotic (Tubb3, Gad65/67, Lhx6 and Tbr1) cells. Our experiments show that Abracl protein has, compared to the mRNA, a broader expression domain, including, apart from proliferating cells of the subpallial and diencephalic SVZ, post-mitotic cells occupying the subpallial and pallial mantle (including the CP), as well as subpallial-derived migrating interneurons. Interestingly, in late embryonic developmental stages, Abracl was also transiently detected in major telencephalic fiber tracts.

Alterations in Faecal Microbiota and Elevated Levels of Intestinal IgA Following Oral Administration of Lacticaseibacillus casei in mice.

The intestinal microbiota has been identified as a crucial regulator of the overall health, with studies describing its influence in a variety of disorders and developmental processes throughout the body. A widely accepted approach of influencing the microbiota and regulating its functionality in health or disease is the consumption of probiotics. In this study, we aimed to identify the impact of probiotic Lacticaseibacillus casei ATCC393 on the intestinal microbiota of mice and circulating soluble products of microbial origin or the immune system. Investigation of the gut microflora using next-generation sequencing analysis revealed alterations in the microbial populations following consumption of the probiotic. Abundance of taxa classified as Muribaculaceae was increased in lactobacilli-fed animals, while abundance of taxa classified as Lachnospiraceae and Oscillospiraceae was decreased. In addition, the composition of the intestinal microbiota was modified by the administration of L. casei, as evident by the clustering of test subjects when inspecting beta diversity, without however any significant effect on the alpha diversity of the animals. Finally, production of IgA in the intestinal lumen of mice that had received the microorganism was significantly increased, as was the concentration of lactic acid, while levels of acetic acid were noticeably lower in the L. casei group. The findings suggest that L. casei can be considered a potential candidate strain for the modulation of intestinal homeostasis and a component of dietary interventions aiming to improve overall health.

Gut Barrier Disruption Secondary to Radiofrequency-Assisted Liver Parenchyma Resection in a Porcine Model.

BACKGROUND: Radiofrequency-assisted liver resection (RF-LR) techniques minimize intraoperative blood loss, while avoiding the Pringle maneuver. Both surgical excision and radiofrequency ablation of liver parenchyma compromise gut barrier function with subsequent bacterial translocation. The present study sought to investigate in a porcine model the impact of two RF-LR techniques on the integrity and inflammatory response of the gut barrier. METHODS: Twenty-four pigs were subjected to either (a) partial hepatectomy (PH) employing the "sequential coagulate-cut" technique using a monopolar electrode (SCC group), the one using the bipolar Habib-4X device (group H), or the "crush-clamp" technique (group CC) or (b) sham operation (group Sham). At 48-h post-operation, ileal tissue was excised to be subjected to histopathologic examination, histomorphometric analysis, and immunohistochemical assessment of the mitotic and apoptotic activities and the expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), and nuclear factor-κB (NFκΒ). RESULTS: Histopathologic score increased in all PH groups, being higher in group SCC, while lower in group H. Villous height decreased in group SCC only. Mitotic index decreased, while apoptotic index increased in all PH groups. An increase in tissue expression score was noted for IL-6 in group CC, for TNFα in all PH groups, being lower in group H compared to group CC, and for NFκB in all PH groups. CONCLUSIONS: The Habib-4X technique for liver resection proved to preserve the integrity of gut barrier, being less injurious in the intestinal mucosa compared to the SCC and CC techniques.

Gut-Barrier Disruption After Laparoscopic Versus Open Major Liver Resection in the Rat.

BACKGROUND: Major liver resection may compromise gut-barrier function, increasing the risk of postoperative infectious complications. The aim of the present experimental study was to compare the effect of the laparoscopic versus the open technique for major liver resection on integrity as well as inflammatory and immune responses of the gut barrier. METHODS: Wistar rats were subjected to open 70% hepatectomy (group H), laparoscopic 70% hepatectomy (group LH), sham operation (group S) or no intervention (group C). At various timepoints (1 hour-1 week) after operation, ileal tissue was excised for oxidative state assessment (TBARS levels), histopathologic examination, histomorphometric analysis, immunohistochemical assessment of the mitotic and apoptotic activity, and tissue expression of inflammatory (interleukin-6, tumor necrosis factor-α, nuclear factor-κB and vascular cell adhesion molecule-1) and immune response biomarkers (CD4+ and CD8+ T-lymphocytes) of the intestinal mucosa. RESULTS: No changes were noted in oxidative state. The histopathologic profile was less deteriorated in group LH compared to group H. Intestinal mucosa atrophy was less intense in group LH compared to group H and was related to an equally compromised crypt cell mitotic activity. Tissue overexpression of interleukin-6, tumor necrosis factor-α, nuclear factor-κΒ, vascular cell adhesion molecule-1, CD4+, and CD8+ T-lymphocytes was less pronounced in group LH compared to group H. CONCLUSION: The employment of the laparoscopic technique for major liver resection in the rat attenuated disruption of the gut barrier compared to the open procedure. This was related to less pronounced inflammatory and immune responses of the intestinal mucosa.

Biogenic selenium nanoparticles produced by Lactobacillus casei ATCC 393 inhibit colon cancer cell growth in vitro and in vivo.

Selenium compounds exhibit excellent anticancer properties but have a narrow therapeutic window. Selenium nanoparticles, however, are less toxic compared to other selenium forms, and their biogenic production leads to improved bioavailability. Herein, we used the probiotic strain Lactobacillus casei ATCC 393, previously shown to inhibit colon cancer cell growth, to synthesize biogenic selenium nanoparticles. We examined the anticancer activity of orally administered L. casei, L. casei-derived selenium nanoparticles and selenium nanoparticle-enriched L. casei, and investigated their antitumor potential in the CT26 syngeneic colorectal cancer model in BALB/c mice. Our results indicate that L. casei-derived selenium nanoparticles and selenium nanoparticle-enriched L. casei exert cancer-specific antiproliferative activity in vitro. Moreover, the nanoparticles were found to induce apoptosis and elevate reactive oxygen species levels in cancer cells. It is noteworthy that, when administered orally, selenium nanoparticle-enriched L. casei attenuated the growth of colon carcinoma in mice more effectively than the isolated nanoparticles or L. casei, suggesting a potential additive effect of the nanoparticles and the probiotic. To the best of our knowledge this is the first comparative study examining the anticancer effects of selenium nanoparticles synthesized by a microorganism, the selenium nanoparticle-enriched microorganism and the sole microorganism.

Magnetic resonance imaging for early pregnancy diagnosis in the laboratory rat.

Pregnancy diagnosis and embryo counting are important end points in reproductive, developmental biology and toxicology studies. The purpose of the present study was to assess the feasibility and efficacy of magnetic resonance imaging (MRI) for early pregnancy diagnosis and embryo counting in the laboratory rat. Female Wistar rats were subjected to whole-body MRI scanning using a 1.5T MRI scanner, employing a isotropic T2-weighted 3D short-tau inversion recovery sequence from day 8 to day 12 post coitum (pc) or without prior mating, under general anaesthesia for pregnancy diagnosis and embryo counting. MRI examination was followed by laparotomy and visual inspection of the uterus to verify MRI findings. By day 8 pc, uterine bulges, characteristic of pregnancy, were depicted as oval-shaped structures of high intensity signal. By day 10 pc, embryonic vesicles were detected at the medial side of the uterine bulges. Pregnancy was diagnosed with 0% false-negative diagnosis and 100% accuracy by day 11 pc, while embryos were counted with 100% accuracy by day 12 pc. In conclusion, MRI proved to be a feasible and reliable non-invasive imaging method of early pregnancy diagnosis and embryo counting in the laboratory rat.

Assessment of the Immunomodulatory Properties of the Probiotic Strain Lactobacillus paracasei K5 in vitro and In Vivo.

Lactobacillus paracasei K5 is a lactic acid bacteria (LAB) strain that has been isolated from dairy products. Previous studies have established its probiotic potential in a series of in vitro tests, including molecular characterization, safety profiling, and tolerability of the gastrointestinal tract conditions. To characterize its beneficial actions on the host, we have shown previously that L. paracasei K5 adheres to Caco-2 cells and exerts anti-proliferative effects through the induction of apoptosis. In the present study, we focused on the immunomodulatory potential of this strain. We employed the dorsal-air-pouch mouse model of inflammation and recorded an eight-fold increase in the recruitment of immune cells in mice treated with the probiotic strain, compared to the control group. Analysis of the exudates revealed significant changes in the expression of pro-inflammatory mediators on site. Treatment of Caco-2 cells with L. paracasei K5 induced significant upregulation of cytokines interleukin-1α (IL-1α), ΙL-1ß, IL-6, tumor necrosis factor-alpha (TNF-α), the chemokine C-X-C motif ligand 2 (CXCL2), and the inflammation markers soluble intercellular adhesion molecule (sICAM) and metallopeptidase inhibitor-1 (TIMP-1). Transient induction of the Toll-like receptors (TLRs) 2, 4, 6, and 9 expression levels was recorded by real-time PCR analysis. These results highlight the immunomodulatory potential of this strain and further support its probiotic character.

Immune Responses Raised in an Experimental Colon Carcinoma Model Following Oral Administration of Lactobacillus casei.

The role of dietary probiotic strains on host anticancer immune responses against experimental colon carcinoma was investigated. We have previously shown that Lactobacillus casei administration led to tumor growth suppression in an experimental colon cancer model. Here, we investigated the underlying immune mechanisms involved in this tumorgrowth inhibitory effect. BALB/c mice received daily live lactobacilli per os prior to the establishment of a syngeneic subcutaneous CT26 tumor. Tumor volume, cytokine production, T cell differentiation and migration, as well as tumor cell apoptosis were examined to outline potential immunomodulatory effects following L. casei oral intake. Probiotic administration in mice resulted in a significant increase in interferon gamma (IFNγ), Granzyme B and chemokine production in the tumor tissue as well as enhanced CD8+ T cell infiltration, accompanied by a suppression of tumor growth. Cytotoxic activity against cancer cells was enhanced in probioticfed compared to control mice, as evidenced by the elevation of apoptotic markers, such as cleaved caspase 3 and poly (ADPribose) polymerase 1 (PARP1), in tumor tissue. Oral administration of Lactobacillus casei induced potent Th1 immune responses and cytotoxic T cell infiltration in the tumor tissue of tumorbearing mice, resulting in tumor growth inhibition. Thus, the microorganism may hold promise as a novel dietary immunoadjuvant in raising protective anticancer immune responses.

Effect of laparoscopic liver resection versus the open technique on hepatocyte regenerating activity in the rat.

BACKGROUND: Laparoscopic liver resection offers a safe and feasible option primarily for the excision of hepatic neoplasms. Timely recovery of liver volume is a key factor for improving prognosis and post-operative mortality of patients undergone liver resection. The aim of the present study was to compare liver regeneration after laparoscopic over open partial hepatectomy. METHODS: Wistar rats were subjected to laparoscopic 70% hepatectomy (group LAP-HEP), open 70% hepatectomy (group HEP), sham operation (group Sham) or no intervention (group Control). At various timepoints following operation (1 h-2 weeks), the liver was excised to assess relative liver weight, thiobarbituric acid reactive substances (TBARS) levels, mitotic activity, tissue expression of Nuclear Factor-κB (NFκB), Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) and the histopathologic profile. RESULTS: No differences were seen in relative liver weight between hepatectomy groups. Mitotic index was increased in all operative study groups, being higher in group LAP-HEP than in group HEP. TBARS levels were higher in group LAP-HEP compared to group HEP. NFκB and VCAM-1 tissue expression scores were increased in all operative study groups with VCAM-1 being higher in group HEP, while ICAM-1 was overexpressed only in hepatectomy groups. Mild histopathologic lesions were noted in hepatectomy groups with the histopathologic score being higher in group HEP (24 h). CONCLUSIONS: Laparoscopic liver resection enhanced hepatocyte mitotic activity which was accompanied by mild oxidative stress and a less pronounced local inflammatory response and tissue injury to that of the open technique.

Spontaneous pancreatic undifferentiated pleomorphic sarcoma in a laboratory rat: A case report.

We present a case of spontaneous undifferentiated/unclassified sarcoma, of a pleomorphic subtype formerly known as malignant fibrous histiocytoma (UPS/MFH), arising from the pancreas of a laboratory rat. The mass was excised after laparotomy from a 6-month-old female laboratory Wistar rat. It presented a giant multilobulated mass of irregular shape, which had arisen from the pancreas and occupied almost the entire peritoneal cavity. Histologically the tumor was characterized by a highly variable morphological pattern, with frequent transitions from storiform to pleomorphic areas. An extensive immunohistochemical examination revealed no specific lines of differentiation. Immunohistochemical positivity was observed only to MIB-1 (high Ki-67 proliferation index), vimentin and CD68 antibodies. The diagnosis was compatible with UPS/MFH. To the best of our knowledge, the present case is the first report of a spontaneous primary UPS/MFH arising from the pancreas of a laboratory rat.

Learning to detect chest radiographs containing pulmonary lesions using visual attention networks.

Machine learning approaches hold great potential for the automated detection of lung nodules on chest radiographs, but training algorithms requires very large amounts of manually annotated radiographs, which are difficult to obtain. The increasing availability of PACS (Picture Archiving and Communication System), is laying the technological foundations needed to make available large volumes of clinical data and images from hospital archives. Binary labels indicating whether a radiograph contains a pulmonary lesion can be extracted at scale, using natural language processing algorithms. In this study, we propose two novel neural networks for the detection of chest radiographs containing pulmonary lesions. Both architectures make use of a large number of weakly-labelled images combined with a smaller number of manually annotated x-rays. The annotated lesions are used during training to deliver a type of visual attention feedback informing the networks about their lesion localisation performance. The first architecture extracts saliency maps from high-level convolutional layers and compares the inferred position of a lesion against the true position when this information is available; a localisation error is then back-propagated along with the softmax classification error. The second approach consists of a recurrent attention model that learns to observe a short sequence of smaller image portions through reinforcement learning; the reward function penalises the exploration of areas, within an image, that are unlikely to contain nodules. Using a repository of over 430,000 historical chest radiographs, we present and discuss the proposed methods over related architectures that use either weakly-labelled or annotated images only.

Spatial distribution of the full-length members of the Grg family during embryonic neurogenesis reveals a "Grg-mediated repression map" in the mouse telencephalon.

The full-length members of the Groucho/Transducin-like Enhancer of split gene family, namely Grg1-4, encode nuclear corepressors that act either directly, via interaction with transcription factors, or indirectly by modifying histone acetylation or chromatin structure. In this work we describe a detailed expression analysis of Grg1-4 family members during embryonic neurogenesis in the developing murine telencephalon. Grg1-4 presented a unique, complex yet overlapping expression pattern; Grg1 and Grg3 were mainly detected in the proliferative zones of the telencephalon, Grg2 mainly in the subpallium and finally, Grg4 mainly in the subpallial post mitotic neurons. In addition, comparative analysis of the expression of Grg1-4 revealed that, at these stages, distinct telencephalic progenitor domains or structures are characterized by the presence of different combinations of Grg repressors, thus forming a "Grg-mediated repression map".

Laparoscopic early pregnancy diagnosis in the laboratory rat.

Timely and accurate diagnosis of pregnancy in the laboratory rat is an invaluable endpoint in embryological and reproductive toxicology studies. The purpose of the present study was to assess the feasibility, sensitivity, accuracy and safety of laparoscopic examination of the uterus for detecting pregnancy at an early stage, and defining the number of fetuses in surviving rat models. Female Wistar rats were subjected to a two-port laparoscopic examination of their uterus from day 6 to day 10 post-coitum (pc). Mean recovery time from anesthesia was 148 ± 66 s. A postoperative 4.0 ± 1.8% body weight loss was restored in 3.9 ± 1.3 days. Uterine bulges suggestive of underlying embryonic vesicles could be detected by day 7 pc with a 0% false-negative diagnosis. Comparison of the number of laparoscopically defined uterine bulges (fetal counts) with litter size revealed a 0% underestimation rate of fetal counts, and a 42.9-87.5% overestimation rate from day 7 to day 10 pc. In conclusion, the present study introduced the laparoscopic examination of the uterus and showed it to be a feasible, reliable and safe method of early pregnancy diagnosis in the laboratory rat by day 7 pc.

Immune and Inflammatory Responses of the Intestinal Mucosa following Extended Liver Radiofrequency Ablation.

BACKGROUND AND AIM: Extended liver radiofrequency ablation (RFA) has been shown to disrupt gut barrier integrity with subsequent bacterial translocation. The aim of the present project was to study the immune and inflammatory responses of the intestinal mucosa after extended RFA of the liver. METHODS: Twelve Wistar rats were either subjected to RFA of the left lateral hepatic lobe (approximately 30% of the liver mass) after midline laparotomy (group RFA, n = 6) or sham operation (group Sham, n = 6). Forty-eight hours later, ileal tissue specimens were excised for immunohistochemical assessment of CD68+ macrophages, CD4+ T-lymphocytes, CD8+ T-lymphocytes, mucosal addressin cell adhesion molecule-1 (MAdCAM-1), tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and nuclear factor-κB (NFκB) expression. RESULTS: Immune response biomarkers were upregulated in the RFA group. Expression of CD4+ and CD8+ T-lymphocytes was moderate, while that of CD68+ macrophages and MAdCAM-1 was high. Inflammatory response biomarkers were also upregulated in the RFA group. TNFα, IL-6, and NFκB expression was low, moderate, and high, respectively. CONCLUSIONS: Extended liver RFA evokes both immune and inflammatory responses of the gut mucosa.

Tissue injury of the remnant liver following radiofrequency-assisted partial hepatectomy.

PURPOSE: To evaluate remnant liver tissue damage in a pig model of radiofrequency (RF)-assisted liver resection employing either the sequential coagulate cut (SCC) Belgrade technique using a monopolar RF electrode or the one using the bipolar Habib-4x device. METHODS: Sixteen pigs underwent either a) resection of part of the left lateral and left median hepatic lobes employing the SCC (SCC group), the Habib-4X (H group) or the "crushclamp" technique (CC group) or b) sham operation (Sham group). Forty-eight hours later, tissue specimens were excised from the right lateral hepatic lobe for histopathological examination and immunohistochemical assessment of tissue injury, mitosis and inflammation. RESULTS: Histopathologic lesions, apoptotic activity, HSP 40 and TNFα expression were more intense, while mitotic activity was less prominent in the SCC group technique compared to H group. Comparison between CC and H groups suggested the pivotal role of partial hepatectomy (PH) per se in the changes noted in H group. CONCLUSION: The Habib-4X liver resection technique proved to be less injurious in the remnant liver tissue after PH compared to the SCC technique.

Microscopic assessment of the tissue-sparing potential of radiofrequency-assisted liver resection techniques in a porcine model.

BACKGROUND: The aim of the present study was to microscopically assess the tissue-sparing potential of contemporary radiofrequency-assisted liver resection (RF-LR) techniques. METHODS: Twenty-four pigs were subjected to either (1) partial hepatectomy (PH) using the sequential-coagulate-cut (SCC) technique (group SCC, n = 6) using a monopolar electrode, the technique using the bipolar electrode Habib-4X (group H, n = 6) or the "crush-clamp" technique (group CC, n = 6); or (2) sham operation (group Sham, n = 6). At 48 h post-operation, liver parenchyma proximal to the ablation rim was excised for histopathologic examination and immunohistochemical assessment of apoptosis (antibody M30) and inflammatory response (antibodies IL-6, TNFα and NFκB). RESULTS: Histopathologic index increased from the 1st to the 4th , the 1st to the 2nd or only the 1st cm from the inner margin of the ablation rim in group SCC, H or CC, respectively. The index was higher in group SCC compared to the other groups. Tissue expression of M30, IL-6, TNFα and NFκB increased in all PH groups, being higher and more expanded in group SCC, H, SCC and SCC, respectively. CONCLUSIONS: RF-LR techniques had variable microscopically assessed tissue-sparing effect. The Habib-4X proved to be less injurious compared to the SCC Belgrade technique regarding the severity and extent of tissue damage proximal to the ablation rim.

Survival, Intestinal Mucosa Adhesion, and Immunomodulatory Potential of Lactobacillus plantarum Strains.

Survival during transit through the gastrointestinal track, intestinal mucosa adhesion, and a potential immunomodulatory effect of Lactobacillus plantarum strains 2035 and ACA-DC 2640 were investigated in a rat model. According to microbiological and multiplex PCR analysis, both strains were detected in feces 24 h after either single-dose or daily administration for 7 days. Intestinal mucosa adhesion of L. plantarum 2035 was noted in the large intestine at 24 h after single-dose administration, while it was not detected at 48 h. Daily dosing, prolonged detection of the strain up to 48 h post-administration, and expanded adhesion to the small intestine. Adhesion of L. plantarum ACA-DC 2640 to the intestinal mucosa after single-dose administration was prolonged and more extended compared to L. plantarum 2035. Daily dosing increased both the levels and the rate of positive cultures of the strains compared to those of the single-dose scheme. In addition, both strains increased total IgG while decreased IgM and IgA serum levels. In conclusion, L. plantarum 2035 and L. plantarum ACA-DC 2640 survived transit through the gastrointestinal track, exhibited transient distinct adhesion to the intestinal mucosa and modulated the systemic immune response.

A laparoscopic technique of partial hepatectomy in the rat.

BACKGROUND: Laparoscopic partial hepatectomy is an increasingly applied technique in the treatment of liver tumors and in living donor transplantation. There is a need for establishing an animal model that would facilitate experimental research on the technique. The aim of the present study was to describe a safe and efficient laparoscopic technique of 70% partial hepatectomy in the rat. MATERIALS AND METHODS: Twenty-four male Wistar rats underwent either laparoscopic (group LAP-HEP) or open resection of the median and left lateral hepatic lobes (group HEP). In group LAP-HEP, a 5-mm Hg pneumoperitoneum was established. Three 5-mm trocars were introduced in the abdominal cavity. A self-made pretied ligature loop was used to ligate en bloc the pedicles of the hepatic lobes to be resected. A self-made sterile elastic specimen retrieval bag facilitated extraction of the resected liver tissue. In group HEP, the same liver lobes were resected by ligation of their pedicles after midline laparotomy. RESULTS: The percentage of resected liver parenchyma did not differ between groups. All animals returned to normal feeding activity by 48 h postoperation and had no complications. CONCLUSIONS: A simple, cost-effective, safe, and efficient laparoscopic technique for 70% partial hepatectomy in the rat was described.

Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9) CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9) CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.

HSPC280, a winged helix protein expressed in the subventricular zone of the developing ganglionic eminences, inhibits neuronal differentiation.

Winged helix proteins have critical roles in a variety of developmental processes. During a screening for genes expressed in the developing forebrain, we identified HSPC280, a non-typical winged helix protein, which shares similarity with a protein-protein interaction domain found in the proteins of the actin-binding Rho-activating protein family. In this work, we analyzed HSPC280 expression during mouse development as well as during neuronal differentiation of mouse Neuro2a cells. HSPC280 expression is tightly regulated; during mouse development, it was detected predominantly in the ganglionic eminences of the ventral telencephalon, from their appearance at E11.5 to P0, with the highest levels between E13.5 and E15.5, a period that correlates with the peak of neurogenesis in these structures. Comparative expression analysis of HSPC280 with Dlx2, cyclinD2 and Lhx6 revealed that, within the ganglionic eminences, HSPC280 was restricted in the proliferating cell population of the subventricular zone, in a pattern similar to that of cyclinD2. Finally, we showed that HSPC280 is a nuclear protein which, when overexpressed in Neuro2a cells, it inhibited neuronal differentiation in vitro, suggesting its involvement in the mechanisms controlling neural progenitor cells proliferation.