Three-Dimensional Digital Reconstruction of the Cerebellar Cortex: Lobule Thickness, Surface Area Measurements, and Layer Architecture.

The cerebellum is ontogenetically one of the first structures to develop in the central nervous system; nevertheless, it has been only recently reconsidered for its significant neurobiological, functional, and clinical relevance in humans. Thus, it has been a relatively under-studied compared to the cerebrum. Currently, non-invasive imaging modalities can barely reach the necessary resolution to unfold its entire, convoluted surface, while only histological analyses can reveal local information at the micrometer scale. Herein, we used the BigBrain dataset to generate area and point-wise thickness measurements for all layers of the cerebellar cortex and for each lobule in particular. We found that the overall surface area of the cerebellar granular layer (including Purkinje cells) was 1,732 cm2 and the molecular layer was 1,945 cm2. The average thickness of the granular layer is 0.88 mm (± 0.83) and that of the molecular layer is 0.32 mm (± 0.08). The cerebellum (both granular and molecular layers) is thicker at the depth of the sulci and thinner at the crowns of the gyri. Globally, the granular layer is thicker in the lateral-posterior-inferior region than the medial-superior regions. The characterization of individual layers in the cerebellum achieved herein represents a stepping-stone for investigations interrelating structural and functional connectivity with cerebellar architectonics using neuroimaging, which is a matter of considerable relevance in basic and clinical neuroscience. Furthermore, these data provide templates for the construction of cerebellar topographic maps and the precise localization of structural and functional alterations in diseases affecting the cerebellum.

The Postnatal Offspring of Finasteride-Treated Male Rats Shows Hyperglycaemia, Elevated Hepatic Glycogen Storage and Altered GLUT2, IR, and AR Expression in the Liver.

BACKGROUND: A growing body of data indicates that the physiology of the liver is sex-hormone dependent, with some types of liver failure occurring more frequently in males, and some in females. In males, in physiological conditions, testosterone acts via androgen receptors (AR) to increase insulin receptor (IR) expression and glycogen synthesis, and to decrease glucose uptake controlled by liver-specific glucose transporter 2 (GLUT-2). Our previous study indicated that this mechanism may be impaired by finasteride, a popular drug used in urology and dermatology, inhibiting 5α-reductase 2, which converts testosterone (T) into dihydrotestosterone (DHT). Our research has also shown that the offspring of rats exposed to finasteride have an altered T-DHT ratio and show changes in their testes and epididymides. Therefore, the goal of this study was to assess whether the administration of finasteride had an trans-generational effect on (i) GLUT-2 dependent accumulation of glycogen in the liver, (ii) IR and AR expression in the hepatocytes of male rat offspring, (iii) a relation between serum T and DHT levels and the expression of GLUT2, IR, and AR mRNAs, (iv) a serum glucose level and it correlation with GLUT-2 mRNA. METHODS: The study was conducted on the liver (an androgen-dependent organ) from 7, 14, 21, 28, and 90-day old Wistar male rats (F1:Fin) born by females fertilized by finasteride-treated rats. The control group was the offspring (F1:Control) of untreated Wistar parents. In the histological sections of liver the Periodic Acid Schiff (PAS) staining (to visualize glycogen) and IHC (to detect GLUT-2, IR, and AR) were performed. The liver homogenates were used in qRT-PCR to assess GLUT2, IR, and AR mRNA expression. The percentage of PAS-positive glycogen areas were correlated with the immunoexpression of GLUT-2, serum levels of T and DHT were correlated with GLUT-2, IR, and AR transcript levels, and serum glucose concentration was correlated with the age of animals and with the GLUT-2 mRNA by Spearman's rank correlation coefficients. RESULTS: In each age group of F1:Fin rats, the accumulation of glycogen was elevated but did not correlate with changes in GLUT-2 expression. The levels of GLUT-2, IR, and AR transcripts and their immunoreactivity statistically significantly decreased in F1:Fin animals. In F1:Fin rats the serum levels of T and DHT negatively correlated with androgen receptor mRNA. The animals from F1:Fin group have statistically elevated level of glucose. Additionally, in adult F1:Fin rats, steatosis was observed in the liver (see Appendix A). CONCLUSIONS: It seems that treating male adult rats with finasteride causes changes in the carbohydrate metabolism in the liver of their offspring. This can lead to improper hepatic energy homeostasis or even hyperglycaemia, insulin resistance, as well as some symptoms of metabolic syndrome and liver steatosis.

Bioprinting of Multiscaled Hepatic Lobules within a Highly Vascularized Construct.

Highly vascularized complex liver tissue is generally divided into lobes, lobules, hepatocytes, and sinusoids, which can be viewed under different types of lens from the micro- to macro-scale. To engineer multiscaled heterogeneous tissues, a sophisticated and rapid tissue engineering approach is required, such as advanced 3D bioprinting. In this study, a preset extrusion bioprinting technique, which can create heterogeneous, multicellular, and multimaterial structures simultaneously, is utilized for creating a hepatic lobule (≈1 mm) array. The fabricated hepatic lobules include hepatic cells, endothelial cells, and a lumen. The endothelial cells surround the hepatic cells, the exterior of the lobules, the lumen, and finally, become interconnected with each other. Compared to hepatic cell/endothelial cell mixtures, the fabricated hepatic lobule shows higher albumin secretion, urea production, and albumin, MRP2, and CD31 protein levels, as well as, cytochrome P450 enzyme activity. It is found that each cell type with spatial cell patterning in bioink accelerates cellular organization, which could preserve structural integrity and improve cellular functions. In conclusion, preset extruded hepatic lobules within a highly vascularized construct are successfully constructed, enabling both micro- and macro-scale tissue fabrication, which can support the creation of large 3D tissue constructs for multiscale tissue engineering.

Are Vermal Lobules VI-VII Smaller in Autism Spectrum Disorder?

Cerebellar volume, in particular vermal lobule areas VI-VII, have been extensively researched in individuals with autism spectrum disorder (ASD), although findings are often unclear. The aim of the present study is to consolidate all existing cerebellar and age data of individuals with ASD, and compare this data to typically developing (TD) controls. Raw data, or the means and standard deviations of cerebellar volume and age, were obtained from 17 studies (NCerebellum: 421 ASD and 370 TD participants; NVI-VII: 506 ASD and 290 TD participants). Total cerebellar volume, or VI-VII area, was plotted against age and lines of fit of ASD and TD data were compared. Mean differences in cerebellar volume and VI-VII area between participants with ASD and TD participants were then compared via ANCOVA analyses. Findings revealed multiple differences in VI-VII area between participants with ASD and TD participants below 18 years of age. Additionally, cerebellar volume was greater in males with ASD than TD males between 2 and 4 years. In the present study, cerebellar volume and VI-VII area show different rates of change across age for those with autism compared with those without. These morphological differences provide a neurobiological justification to investigate related behavioural correlates.

Clonal analysis reveals granule cell behaviors and compartmentalization that determine the folded morphology of the cerebellum.

The mammalian cerebellum consists of folds of different sizes and shapes that house distinct neural circuits. A crucial factor underlying foliation is the generation of granule cells (gcs), the most numerous neuron type in the brain. We used clonal analysis to uncover global as well as folium size-specific cellular behaviors that underlie cerebellar morphogenesis. Unlike most neural precursors, gc precursors divide symmetrically, accounting for their massive expansion. We found that oriented cell divisions underlie an overall anteroposteriorly polarized growth of the cerebellum and gc clone geometry. Clone geometry is further refined by mediolateral oriented migration and passive dispersion of differentiating gcs. Most strikingly, the base of each fissure acts as a boundary for gc precursor dispersion, which we propose allows each folium to be regulated as a developmental unit. Indeed, the geometry and size of clones in long and short folia are distinct. Moreover, in engrailed 1/2 mutants with shorter folia, clone cell number and geometry are most similar to clones in short folia of wild-type mice. Thus, the cerebellum has a modular mode of development that allows the plane of cell division and number of divisions to be differentially regulated to ensure that the appropriate number of cells are partitioned into each folium.

Rapid automatic segmentation of the human cerebellum and its lobules (RASCAL)--implementation and application of the patch-based label-fusion technique with a template library to segment the human cerebellum.

Reliable and fast segmentation of the human cerebellum with its complex architecture of lobes and lobules has been a challenge for the past decades. Emerging knowledge of the functional integration of the cerebellum in various sensori-motor and cognitive-behavioral circuits demands new automatic segmentation techniques, with accuracies similar to manual segmentations, but applicable to large subject numbers in a reasonable time frame. This article presents the development and application of a novel pipeline for rapid automatic segmentation of the human cerebellum and its lobules (RASCAL) combining patch-based label-fusion and a template library of manually labeled cerebella of 16 healthy controls from the International Consortium for Brain Mapping (ICBM) database. Leave-one-out experiments revealed a good agreement between manual and automatic segmentations (Dice kappa = 0.82). Intraclass correlation coefficients (ICC) were calculated to test reliability of segmented volumes and were highest (ICC > 0.9) for global measures (total and hemispherical grey and white matter) followed by larger lobules of the posterior lobe (ICC > 0.8). Further we applied the pipeline to all 152 young healthy controls of the ICBM database to look for hemispheric and gender differences. The results demonstrated larger native space volumes in men then women (mean (± SD) total cerebellar volume in women = 217 cm(3) (± 26), men = 259 cm(3) (± 29); P < 0.001). Significant gender-by-hemisphere interaction was only found in stereotaxic space volumes for white matter core (men > women) and anterior lobe volume (women > men). This new method shows great potential for the precise and efficient analysis of the cerebellum in large patient cohorts.

Positioning of leukocyte subsets in the portal and lobular compartments of hepatitis C virus-infected liver correlates with local chemokine expression.

BACKGROUND AND AIM: Chronic hepatitis C virus infection is characterized by infiltration of a mixed population of leukocytes into portal tracts and infiltration almost exclusively by CD8+ T cells into lobules of the liver. This pattern of leukocyte recruitment is likely to be orchestrated in a cell-specific fashion by local chemokine expression. METHODS: Portal or lobular tissues were isolated by laser capture microdissection from 17 liver biopsy specimens to examine regional gene expression of a panel of chemokine ligands and receptors. The biopsies were also stained immunohistochemically to enumerate regional cell numbers. RESULTS: Expression of multiple chemokine ligands and receptors was evident, although few correlated with leukocyte numbers. In the lobule, expression of CXCL10 correlated with T-cell subsets (CD3+, P = 0.0002; CD4+, P = 0.0053; and CD8+, P = 0.0061), as did CCL5 (CD3+, P = 0.0005; CD8+, P = 0.0199) and CCL3 (CD3+, P = 0.0016; CD8+, P = 0.008). In the portal tracts, expression of CXCL10 and CCL5 was correlated with CD8+ T-cell numbers (P = 0.0040 and P = 0.0114, respectively), whereas CXCL13 was strongly correlated with CD20+ B-cell numbers (P < 0.0001). CXCR3 expression correlated with CD3+ and CD4+ T cells (P < 0.0001 and P = 0.0208, respectively), CCR5 with CD8+ T cells (P < 0.0001), and CXCR5 with CD20+ B-cell infiltration (P = 0.0022). CONCLUSION: CXCR3, CCR5, and CXCR5 and their ligands form key elements of the "zip code" responsible for regional localization of specific lymphocyte subsets in the HCV-infected liver.

In Vivo Human Lacrimal Gland Imaging Using an Ultrasound Biomicroscopy.

PURPOSE: In the present study, we introduce human lacrimal gland imaging using an ultrasound biomicroscopy (UBM) with a soft cover and show their findings. METHODS: The representative UBM findings of palpebral lobes in seven subjects (four with non-Sjögren dry eye syndrome, one with Sjögren syndrome, and two healthy subjects) were described in this study. To prolapse the palpebral lobe, the examiner pulled the temporal part of the upper eyelid in the superotemporal direction and directed the subject to look in the inferonasal direction. We scanned the palpebral lobes longitudinally and transversely using UBM. We used an Aviso UBM with a 50 MHz linear probe and ClearScan. RESULTS: In UBM of two healthy subjects, the echogenicity of the lacrimal gland was lower than that of the sclera and homogeneous. But the parenchyma of a patient with Sjögren dry eye syndrome was quite inhomogeneous compared to the healthy subjects. In two patients with dry eye syndrome, we were able to observe some lobules in the parenchyma. We could find excretory ducts running parallel at the surface of the longitudinal section in some subjects. In the longitudinal UBM scan of a subject, we observed a tubular structure at a depth of 1,500 µm that was considered a blood vessel. It ran from the superonasal to the inferotemporal direction. In a subject, we observed a large cyst beneath the conjunctiva. CONCLUSIONS: Lacrimal gland imaging using UBM has both advantages of optical coherence tomography and sonography, and could be useful for evaluating dry eye syndrome.

Biomimetic hepatic lobules from three-dimensional imprinted cell sheets.

Liver-tissue engineering has proven valuable in treating liver diseases, but the construction of liver tissues with high fidelity remains challenging. Here, we present a novel three-dimensional (3D)-imprinted cell-sheet strategy for the synchronous construction of biomimetic hepatic microtissues with high accuracy in terms of cell type, density, and distribution. To achieve this, the specific composition of hepatic cells in a normal human liver was determined using a spatial proteogenomics dataset. The data and biomimetic hepatic micro-tissues with hexagonal hollow cross-sections indicate that cell information was successfully generated using a homemade 3D-imprinted device for layer-by-layer imprinting and assembling the hepatic cell sheets. By infiltrating vascular endothelial cells into the hollow section of the assembly, biomimetic hepatic microtissues with vascularized channels for nutrient diffusion and drug perfusion can be obtained. We demonstrate that the resultant vascularized biomimetic hepatic micro-tissues can not only be integrated into a microfluidic drug-screening liver-on-a-chip but also assembled into an enlarged physiological structure to promote liver regeneration. We believe that our 3D-imprinted cell sheets strategy will open new avenues for biomimetic microtissue construction.

3D Printing of a Vascularized Mini-Liver Based on the Size-Dependent Functional Enhancements of Cell Spheroids for Rescue of Liver Failure.

The emerging stem cell-derived hepatocyte-like cells (HLCs) are the alternative cell sources of hepatocytes for treatment of highly lethal acute liver failure (ALF). However, the hostile local environment and the immature cell differentiation may compromise their therapeutic efficacy. To this end, human adipose-derived mesenchymal stromal/stem cells (hASCs) are engineered into different-sized multicellular spheroids and co-cultured with 3D coaxially and hexagonally patterned human umbilical vein endothelial cells (HUVECs) in a liver lobule-like manner to enhance their hepatic differentiation efficiency. It is found that small-sized hASC spheroids, with a diameter of ≈50 µm, show superior pro-angiogenic effects and hepatic differentiation compared to the other counterparts. The size-dependent functional enhancements are mediated by the Wnt signaling pathway. Meanwhile, co-culture of hASCs with HUVECs, at a HUVECs/hASCs seeding density ratio of 2:1, distinctly promotes hepatic differentiation and vascularization both in vitro and in vivo, especially when endothelial cells are patterned into hollow hexagons. After subcutaneous implantation, the mini-liver, consisting of HLC spheroids and 3D-printed interconnected vasculatures, can effectively improve liver regeneration in two ALF animal models through amelioration of local oxidative stress and inflammation, reduction of liver necrosis, as well as increase of cell proliferation, thereby showing great promise for clinical translation.

Gluteal femoral subcutaneous and dermal adipose tissue in female.

BACKGROUND: During the sexual maturation, gluteal femoral adipose tissue is subjected to numerous modifications, not observable in other regions, in particular in women and less in men. Other authors described this region, but they used imaging techniques having lower resolution, than MRI proposed in this study. High resolution imaging techniques might provide important and more detailed information about the anatomy of gluteal femoral region. METHODS: This study has been performed using 7 T-magnetic resonance imaging and ultrastructural analysis in order to provide accurate description of the subcutaneous adipose tissue and dermis of gluteal femoral region. In this study specimens harvested from cadavers and form living patients have been analyzed. RESULTS: The results showed the presence of three layers: superficial, middle, and deep, characterized by different organization of fat lobules. High resolution imaging showed the adipose papilla that originates from dermis and protrude in subcutaneous adipose tissue. Adipose papilla is characterized by a peculiar morphology with a basement, a neck and a head and these elements represent the functional subunits of adipose papilla. Moreover, ultrastructural study evidenced the relationship between adipocytes and sweat glands, regulated by lipid vesicles. CONCLUSIONS: This study provides important information about subcutaneous and dermal fat anatomy of gluteal femoral region, improving the past knowledge, and move toward a better understanding of the cellulite physiopathology.

Assessing the Location, Relative Expression and Subclass of Dopamine Receptors in the Cerebellum of Hemi-Parkinsonian Rats.

Parkinson's Disease (PD) is a neurodegenerative disease with loss of dopaminergic neurons in the nigrostriatal pathway resulting in basal ganglia (BG) dysfunction. This is largely why much of the preclinical and clinical research has focused on pathophysiological changes in these brain areas in PD. The cerebellum is another motor area of the brain. Yet, if and how this brain area responds to PD therapy and contributes to maintaining motor function fidelity in the face of diminished BG function remains largely unanswered. Limited research suggests that dopaminergic signaling exists in the cerebellum with functional dopamine receptors, tyrosine hydroxylase (TH) and dopamine transporters (DATs); however, much of this information is largely derived from healthy animals and humans. Here, we identified the location and relative expression of dopamine 1 receptors (D1R) and dopamine 2 receptors (D2R) in the cerebellum of a hemi-parkinsonian male rat model of PD. D1R expression was higher in PD animals compared to sham animals in both hemispheres in the purkinje cell layer (PCL) and granule cell layer (GCL) of the cerebellar cortex. Interestingly, D2R expression was higher in PD animals than sham animals mostly in the posterior lobe of the PCL, but no discernible pattern of D2R expression was seen in the GCL between PD and sham animals. To our knowledge, we are the first to report these findings, which may lay the foundation for further interrogation of the role of the cerebellum in PD therapy and/or pathophysiology.

Histomorphological study of hepatic lobules of adult Wistar rats administered with aqueous extracts of leaves of cassia singueana.

OBJECTIVES: Cassia singueana is widely used in northern Nigeria as an herb for the treatment of enamors ailments. Nevertheless the toxicity of the herb on liver architecture; the hepatic lobule and body weight is yet to be authenticated. METHODS: A total of 24 male Wistar rats with an average weight of 150 g were randomly placed into four groups. Each group consisted of 6 rats. Group A served as the control group while groups B, C and D were given 150, 300, and 450 mg of Cassia singueana leaves extract respectively for 14 days. The animals were weighed before, during and after the treatment phase subsequently, they were sacrificed and the liver tissues were processed and stained using hematoxylin and eosin (H&E) stain, Masson's and Trichrome Stain, Gordon and Sweet's Stain, and Periodic Acid Schiff (PAS)Stain. RESULTS: There was no significant change in the animal's body weight of in all the groups when compared to the control group. Our histology result showed that Cassia singueana induced vascular lesion and hepatocytes degeneration putatively though mechanism of cell death (apoptosis and necrosis). It was also found that Cassia singueana has no toxic effect on the reticular fibers of the liver. High dose of Cassia singueana was found to induce the deposition of PAS positive materials in hepatocytes. CONCLUSIONS: The Cassia singueana leaves extract induce hepatocyte degeneration and vascular lesion in the hepatic lobules of the wistar rats, without affecting the animals' body weight.

Structural cerebellar reserve positively influences outcome after severe stroke.

The concept of brain reserve capacity positively influencing the process of recovery after stroke has been continuously developed in recent years. Global measures of brain health have been linked with a favourable outcome. Numerous studies have evidenced that the cerebellum is involved in recovery after stroke. However, it remains an open question whether characteristics of cerebellar anatomy, quantified directly after stroke, might have an impact on subsequent outcome after stroke. Thirty-nine first-ever ischaemic non-cerebellar stroke patients underwent MRI brain imaging early after stroke and longitudinal clinical follow-up. Structural images were used for volumetric analyses of distinct cerebellar regions. Ordinal logistic regression analyses were conducted to associate cerebellar volumes with functional outcome 3-6 months after stroke, operationalized by the modified Rankin Scale. Larger volumes of cerebellar lobules IV, VI, and VIIIB were positively correlated with favourable outcome, independent of the severity of initial impairment, age, and lesion volume (P < 0.01). The total cerebellar volume did not exhibit a significant structure-outcome association. The present study reveals that pre-stroke anatomy of distinct cerebellar lobules involved in motor and cognitive functioning might be linked to outcome after acute non-cerebellar stroke, thereby promoting the emerging concepts of structural brain reserve for recovery processes after stroke.

Histomorphology and Chemical Constituents of Interdigital Gland of Vembur Sheep, Ovis aries.

The interdigital gland is a specialized skin gland located between the digits of Artiodactyla (i.e., even-toed ungulates). Its secretion participates in semiochemical communication, and protects from ultraviolet radiation as well as fungal and bacterial infections of the feet. The present study aimed at finding if there are male-female differences in the anatomy, morphology, and volatile compounds of the interdigital gland of the South Indian breed of Vembur sheep. A total of 24 sheep (12 each of male and female) were spotted at the slaughterhouse and the interdigital gland was removed for examination. The anatomical examination revealed it to resemble a tobacco pipe and to consist of a body, flexure, and excretory duct with an external orifice located at the cleft of the digits. Morphometrically, the interdigital glands differed between males and females. The gland possesses a distinct fibrous capsule, epidermis, and dermis. The fibrous capsule contains several parallel bundles of collagen fibers, nerve fibers, and blood vessels, etc. The epidermis consists of keratinized squamous epithelium formed of stratum basale, stratum granulosum and stratum spinosum. The dermis consists of hair follicles, nerve plexuses, arrector pili muscles, and apocrine and sebaceous glandular lobules. The latter, lined by a simple cuboidal epithelium, are arranged in clusters of acini in the upper portion of the dermis. The apocrine secretory lobules, made up of parenchymal cells, are found in the lower portion of the dermis. The density and diameter of the apocrine and sebaceous secretory lobules were significantly higher in the males than females. Scanning electron microscopic (SEM) analysis confirmed the apocrine and sebaceous secretory components. Twenty-three major compounds were identified in the interdigital gland postings of male and female sheep, among which butanoic acid, 2-methylpropanoic acid, 1-heptanol and octadecanoic acid were present only in the male glandular post, whereas octane, 7-hexyl-tridecane, tetradecane, heptadecane and decanoic acid were present only in the female glandular post. Tetradecanol, tetradecanoic acid and hexadecanol peaks, reportedly antibacterial compounds in pronghorn antelopes, were highly prominent in both male and female sheep. Thus, the interdigital gland of Vembur sheep has two major secretory lobules, namely, sebaceous and apocrine, larger in males than females, which secrete a variety chemical compounds that may serve as chemical communication systems and protect the sheep from foot-borne diseases.

Production of Multiple Cell-Laden Microtissue Spheroids with a Biomimetic Hepatic-Lobule-Like Structure.

The construction of an in vitro 3D cellular model to mimic the human liver is highly desired for drug discovery and clinical applications, such as patient-specific treatment and cell-based therapy in regenerative medicine. However, current bioprinting strategies are limited in their ability to generate multiple cell-laden microtissues with biomimetic structures. This study presents a method for producing hepatic-lobule-like microtissue spheroids using a bioprinting system incorporating a precursor cartridge and microfluidic emulsification system. The multiple cell-laden microtissue spheroids can be successfully generated at a speed of approximately 45 spheroids min-1 and with a uniform diameter. Hepatic and endothelial cells are patterned in a microtissue spheroid with the biomimetic structure of a liver lobule. The spheroids allow long-term culture with high cell viability, and the structural integrity is maintained longer than that of non-structured spheroids. Furthermore, structured spheroids show high MRP2, albumin, and CD31 expression levels. In addition, the in vivo study reveals that structured microtissue spheroids are stably engrafted. These results demonstrate that the method provides a valuable 3D structured microtissue spheroid model with lobule-like constructs and liver functions.

Calcium Signaling in Pancreatic Immune Cells In situ.

Immune cells were identified in intact live mouse pancreatic lobules and their Ca2+ signals, evoked by various agents, characterized and compared with the simultaneously recorded Ca2+ signals in neighboring acinar and stellate cells. Immunochemistry in the live lobules indicated that the pancreatic immune cells most likely are macrophages. In the normal pancreas the density of these cells is very low, but induction of acute pancreatitis (AP), by a combination of ethanol and fatty acids, markedly increased the number of the immune cells. The principal agent eliciting Ca2+ signals in the pancreatic immune cells was ATP, but these cells also frequently produced Ca2+ signals in response to acetylcholine and to high concentrations of bradykinin. Pharmacological studies, using specific purinergic agonists and antagonists, indicated that the ATP-elicited Ca2+ signals were mediated by both P2Y1 and P2Y13 receptors. The pancreatic immune cells were not electrically excitable and the Ca2+ signals generated by ATP were primarily due to release of Ca2+ from internal stores followed by store-operated Ca2+ entry through Ca2+ release-activated Ca2+ channels. The ATP-induced intracellular Ca2+ liberation was dependent on both IP3 generation and IP3 receptors. We propose that the ATP-elicited Ca2+ signal generation in the pancreatic immune cells is likely to play an important role in the severe inflammatory response to the primary injury of the acinar cells that occurs in AP.

Volumetric reduction of cerebellar lobules associated with memory decline across the adult lifespan.

BACKGROUND: The human cerebellum plays an essential role in motor control, is involved in cognitive function and helps to regulate emotional responses. However, little is known about the relationship between cerebellar lobules and age-related memory decline. We aimed to investigate volume alterations in cerebellar lobules at different ages and assess their correlations with reduced memory recall abilities. METHODS: A sample of 275 individuals were divided into the following four groups: 20-35 years (young), 36-50 years (early-middle age), 51-65 years (late-middle age), and 66-89 years (old). Volumes of the cerebellar lobules were obtained using volBrain software. Analysis of covariance and post hoc analysis were used to analyze group differences in cerebellar lobular volumes, and multiple comparisons were performed using the Bonferroni method. Spearman correlation was used to investigate the relationship between lobular volumes and memory recall scores. RESULTS: In this study, we found that older adults had smaller cerebellar volumes than the other subjects. Volumetric decreases in size were noted in bilateral lobule VI and lobule crus I. Moreover, the volumes of bilateral lobule crus I, lobule VI, and right lobule IV were significantly associated with memory recall scores. CONCLUSIONS: In the present study, we found that some lobules of the cerebellum appear more predisposed to age-related changes than other lobules. These findings provide further evidence that specific regions of the cerebellum could be used to assess the risk of memory decline across the adult lifespan.

Functional beta-cells derived from umbilical cord blood mesenchymal stem cells for curing rats with streptozotocin-induced diabetes mellitus.

INTRODUCTION: This study aimed to investigate the therapeutic response to injected human umbilical cord blood mesenchymal stem cells (UCBMSCs) among albino rats with streptozotocin (STZ)-induced diabetes mellitus. METHODS: Control group (GI; n = 25) rats were fed with standard rat diet. Rats with STZ-induced diabetes mellitus without (GII; n = 25) and with (GIII; n = 25) differentiated human UCBMSCs implantation were the test groups. Rats were sacrificed in Week 11 following implantation. Liver biopsies were sectioned and stained in order to highlight both the presence and function of impregnated cells in the liver tissue. RESULTS: Haematoxylin and eosin-stained sections in GI and GII rats showed normal liver architecture while GIII rats showed presence of cell clusters inside the liver tissue and around the central veins. Cell clusters with blue cytoplasm were present in sections in GIII rats but absent in GI and GII rats, indicating the presence of injected differentiated human UCBMSCs. The anti-human insulin immunostaining of GIII rats showed clusters of cells within the liver parenchyma and around central veins, indicating that these cells were active and secreting insulin. CONCLUSION: UCBMSCs are proficient in differentiating into insulin-producing cells in vivo under specific conditions and, when transplanted into the liver of albino rats with STZ-induced diabetes mellitus, were able to secrete insulin and partially control the status of diabetes mellitus in rats.