Cells Lining Research Articles

Synthesis,characterization and biological activities of nitrogen-containing Combretastatin A-4 derivatives

A series of new combretastatin A4 derivatives (6a-6c, 9a-12c) containing nitrogen atoms and nitrogen heterocycles were synthesized by condensation reaction, reduction reaction, hydrolysis reaction and Crutius rearrangement, and the structures were confirmed by 1H NMR, 13C NMR and Mass spectrum. The antitumor cytotoxicity of a series of newly synthesized compounds were evaluated in vitro toward the cell line of hepatoma cell with erianin as positive control. Amoung all the compound, 6b exhibit the most antitumor activity against HepG2 (Human hepatoellular carcinomas) cell line with the inhibition rate 93.85%, and the other compounds also showed moderate to potent antitumor activity. To understand the interaction of series with active binding site of receptor, docking study was performed with VEGFR-2 (Vascular Endothelial Growth Factor Receptor 2) kinase domain in complex with axitinib using Sybyl. The compound with the highest total score was 9c, reaching 8.92, which was higher than that of the positive control erianin This research highlights the therapeutic potential of novel VEGFR-2 inhibitors in treating cancers and provides a promising strategy for drug discovery. Graphical abstract

Synovial Inflammation in Patients with Hallux Valgus is Similar to Changes Seen in Those with Hallux Rigidus

Category: Basic Sciences/Biologics; Bunion Introduction/Purpose: Hallux valgus and hallux rigidus are common disorders that can have functional limitations for patients. Although both involve pathology centered around the first metatarsophalangeal joint (MTPJ), the surgical management for both greatly varies. Inflammatory changes in a joint play a critical role in the development of pain and dysfunction. It has been postulated previously that patients with bunion deformity can develop arthritic changes in the long-term. The purpose of this work is to study and compare the synovial tissue inflammation in patients with hallux valgus and hallux rigidus. Methods: A prospective study of patients aged 25 to 75 years undergoing either surgical management of hallux valgus or hallux rigidus between January 2021 and December 2021 was conducted following IRB approval. Tissue samples from the synovium were collected at the time of procedure and sent for processing and histology. The samples were graded in a blinded fashion based on the degree of inflammation. Morphological features of the synovectomy specimens undergoing histopathologic analysis were scored by synovial lining cell layer hyperplasia, the extent of inflammatory synovium infiltration, as well as pannus formation via activation of synovial stroma and resident cells. All parameters were graded from 0 (absent), 1 (slight), 2 (moderate), to 3 (strong). Statistical analysis was conducted to compare the level of inflammation between patients who had hallux valgus and those that had hallux rigidus. Results: A total of twenty-one samples were collected. One sample was excluded as there was inadequate tissue for analysis. There were eight patients with hallux rigidus and twelve patients with hallux valgus. Mean age at the time of sample collection was 59.3 years (SD=11.9). There was no significant difference in the synovium inflammatory scores (M=5.0, SD=2.25) between the two groups, t(18)= 1.704, p=.106, ([CI .95]: -0.388, 3.722). Moreover, Cohen's effect size value (d=0.78) suggests medium to high practical significance. Conclusion: Understanding the intra-articular impact of hallux valgus is important when considering treatment options. The amount of inflammation in the synovial tissue of hallux valgus patients in this study was similar to that of patients with hallux rigidus suggesting that there is intra-articular inflammation in patients with hallux valgus. Further work will need to be performed to determine if this increased inflammation influences outcomes or has an effect on treatment.

Cystic hygroma in a female suckling pig: a case report

BackgroundCystic hygromas (lymphangiomas) are rarely reported in various animal species, humans included. A hygroma is a benign congenital malformation of the lymphatic drainage system, presenting itself as a mass consisting of multiple cysts of various sizes with a watery content.Case presentationThis report describes clinical, ultrasonographic, and post-mortem findings of a cystic hygroma in a suckling pig. The mass was characterized by a few thin-walled cysts, containing clear yellow serous fluid. Histologically, the central cavity was lined by a single layer of squamous cells, supported by a thick fibrous stroma. On immunohistochemistry, scattered lining cells were weakly positive for Factor-VIII, suggesting their possible endothelial origin.ConclusionsThis case report contributes to raising awareness on this condition in pigs allowing early identification in life so that appropriate care can be provided. The case report attributes to science on hygromas in general, as better understanding of pathologic features, the aetiology and appropriate treatment are needed.

Nanoformulation of Seaweed Eisenia bicyclis in Albumin Nanoparticles Targeting Cardiovascular Diseases: In Vitro and In Vivo Evaluation.

Natural products, especially those derived from seaweeds, are starting to be seen as effective against various diseases, such as cardiovascular diseases (CVDs). This study aimed to design a novel oral formulation of bovine albumin serum nanoparticles (BSA NPs) loaded with an extract of Eisenia bicyclis and to validate its beneficial health effects, particularly targeting hypercholesterolemia and CVD prevention. Small and well-defined BSA NPs loaded with Eisenia bicyclis extract were successfully prepared exhibiting high encapsulation efficiency. Antioxidant activity and cholesterol biosynthesis enzyme 3-hydroxy-3 methylutaryl coenzyme A reductase (HMGR) inhibition, as well as reduction of cholesterol permeation in intestinal lining model cells, were assessed for the extract both in free and nanoformulated forms. The nanoformulation was more efficient than the free extract, particularly in terms of HMGR inhibition and cholesterol permeation reduction. In vitro cytotoxicity and in vivo assays in Wistar rats were performed to evaluate its safety and overall effects on metabolism. The results demonstrated that the Eisenia bicyclis extract and BSA NPs were not cytotoxic against human intestinal Caco-2 and liver HepG2 cells and were also safe after oral administration in the rat model. In addition, an innovative approach was adopted to compare the metabolomic profile of the serum from the animals involved in the in vivo assay, which showed the extract and nanoformulation’s impact on CVD-associated key metabolites. Altogether, these preliminary results revealed that the seaweed extract and the nanoformulation may constitute an alternative natural dosage form which is safe and simple to produce, capable of reducing cholesterol levels, and consequently helpful in preventing hypercholesterolemia, the main risk factor of CVDs.

Cystadenocarcinoma of Bartholin’s gland - Histopathological and immunohistochemical study

Bartholin’s glands are bilateral, mucus-secreting, tubuloacinar glands located within the submucosa of the vulva of ruminants. Seven years old graded Murrah buffalo was reported to have vaginal prolapse. Clinical examination of the vagina revealed a cyst like structure measuring about 7x6 cm and seen on the Bartholin’s gland and on incision it was pink, soft, and fluctuating. The mass was removed as per the standard routine surgical procedure. The mass had a thick wall and contained about 100 ml of clear fluid. The inner side revealed a rough surface and multiple soft raised areas. Microscopical examination revealed invasive, pleomorphic neoplastic epithelial cells that formed irregular tubules and glands with abundant fibrous stroma and inflammation. The tubules were lined by single to double layered eosinophilic anaplastic cuboidal to columnar cells. The proliferated lining cells had large round to oval vesicular nuclei and prominent nucleoli and a few mitotic figures. Some glandular structures were dilated and cystic or irregularly shaped. Local invasion into the surrounding muscles was noticed. Based on gross and histopathological features the case was diagnosed as Bartholin’s gland cystadenocarcinoma. Immunohistochemical staining revealed strong positive reaction with cytokeratin. After treatment, animal recovered uneventfully and there was no recurrence.

FlexMetric bone marrow aspirator yields laboratory and clinically improved results from mesenchymal stem and progenitor cells without centrifugation.

Several devices used to harvest stem/progenitor cells from bone marrow are available to clinicians. This study compared three devices measuring stem cell yields and correlating those yields to bone regeneration. A flexible forward aspirating system Marrow Marxman (MM), a straight needle aspirating on withdrawal system Marrow Cellutions (MC), and a straight needle aspirating on withdrawal and centrifuging the aspirate (BMAC) were compared in a side-to-side patient comparison, as well as tissue engineered bone grafts. The FlexMetric system (MM) produced greater CFU-f values compared to the straight needle (MC) Δ=1083/ml, p<0.001 and 1225/ml, p<0.001 than the BMAC system. This increased stem/progenitor cell yield also translated into a greater radiographic bone density at 6months Δ=88.3 Hu, p≤0.001 versus MC and Δ=116.7, p<0.001 versus BMAC at 6months and Δ=72.2, p<0.001 and Δ=93.3, p<0.001 at 9months respectively. The increased stem/progenitor cell yield of the MM system clinically translated into greater bone regeneration as measured by bone volume p<0.014 and p<0.001 respectively, trabecular thickness p<0.007 and p<0.002 respectively, and trabecular separation p=0.011 and p<0.001. A flexible bone marrow aspirator produces higher yields of stem/progenitor cells. Higher yields of stem/progenitor cells translate into greater bone regeneration in tissue engineering. Flexmetric technology produces better bone regeneration due to a forward aspiration concept reducing dilution from peripheral blood and its ability to target lining cells along the inner cortex. Centrifugation systems are not required in tissue engineering procedures involving stem/progenitor cells due to nonviability or functional loss from g-forces.

Detection of morphometrical, histological and histochemical characteristics of lung and trachea in adult local squirrel (Sciurus anomalus)

The present study aimed to identify the topography, morphology, histochemistry and histology of lung structures, bronchial divisions and trachea in adult local Squirrel (Sciurus anomalus) as a species inhabited in Iraqi environments. This work was conducted on thirty local Squirrel of both sexes (15) males and (15) females were divided into three equal groups, first for http://wsx5customurl.comanatomical perceptions, second to resin cast technique and the third for histological study. Anatomically, in both sexes, the trachea appeared as a cartilaginous structure consisting of flexible cartilaginous rings, C-like, connected by annular ligaments. It begins at the end of the cricoid cartilage from the level of the second cervical vertebra to the fourth thoracic vertebral plane; eventually, it splits into the right and left main bronchi. Count tracheal rings, the entire weight of the lung, full length, the diameter of the trachea and right and left bronchi. The trachea in females was slightly less than in males but not significantly. The bronchial tree was detected in resin cast, which was constructed of the trachea divided into left and right primary bronchi (Main bronchi), the right one was split into four secondary bronchi to enter the right lobes and two secondary bronchi to the left one. The left lung contains one lobe, whereas four lobes were observed in the right. Histologically, the wall of the trachea consists of four layers. Epithelial cells of ciliated pseudostratified columnar and goblet cells that reacted positively with PAS were covered in the mucosa. Submucosa was devoid of the tracheal glands. The Trachealis muscle is connected from the outer aspect of rings. Similarly to the trachea, the primary bronchi are structured but smaller in diameter; they break up within the lung into primary, secondary and tertiary bronchi, then it terminates in respiratory bronchioles that contain Clara cells and open at the end in the sacs of alveoli. Two types of pneumocystis were observed lining the alveoli. The current study concluded anatomically and histologically that there were no significant differences between males and females of local squirrels. The lobulation of the lung in squirrels is different from other animals. The trachea and lung histologically resembled numerous animals, however, the wall had micro morphometric changes. But, the surface lining cells of the tracheal and bronchi mucosa secrete neutral mucin, with no submucosal glands in the tracheal wall. Keywords: Trachea, Local Squirrel, Bronchial Tree, Histochemical, Lung.

Nonacidic thiophene-based derivatives as potential analgesic and design, synthesis, biological evaluation, and metabolic stability study.

Nonsteroidal anti-inflammatory drugs represent one of the most popularly used classes of drugs. However, their long-term administration is associated with various side effects including gastrointestinal ulceration. One of the major reasons of NSAIDs ulcerogenicity is direct damage of the epithelial lining cells by the acidic moieties present in many drugs. Another drawback for this acidic group is its rapid metabolism and clearance through Phase II conjugation. Three series of thiophene and thienopyrimidine derivatives were designed and synthesized as nonacidic anti-inflammatory agents. In vivo testing of their analgesic activity indicated that compounds 2b and 7a-d showed higher PI values than that of the positive control drugs, indomethacin and celecoxib. The latter compounds 2b and 7a-d were subjected to further anti-inflammatory activity testing where they showed comparable percentage edema inhibition to that of indomethacin and celecoxib. Compounds 2b, 7a, 7c, and 7d inhibited PGE2 synthesis by 61.10%-74.54% (71.47% for indomethacin, and 80.11% for celecoxib). The same compounds inhibited the expression of rat mPGES-1 and cPGES3 by 74%-83% (77% for indomethacin, and 82% for celecoxib) and 48%-70% (62% for indomethacin, and 70% for celecoxib), respectively. The stability of the most active compound 2b in Nonenzymatic gastrointestinal fluids and in human plasma was tested. Additionally, studying the metabolic stability of compound 2b in S9 rat liver fraction showed that it displayed a slow in vitro clearance with half-life time 1.5-fold longer than indomethacin. The metabolites of 2b were predicted via UPLC-MS/MS. In silico ADMET profiling study was also included.

Improving Invasive Breast Cancer Care Using Machine Learning Technology

Breast Cancer (BC) is the most common malignancy in women worldwide. In the United States, the lifetime risk of developing an invasive form of breast cancer is 12.5% among women. BC arises in the lining cells (epithelium) of the ducts or lobules in the glandular tissue of the breast. The goal of the present study was to use Machine Learning (ML) as a novel technology to assess and compare the invasive forms of BC including, infiltrating ductal carcinoma, infiltrating lobular carcinoma, and mucinous carcinoma. To achieve this goal, we used ML algorithms and collected a dataset of 334 BC patients available at https://www.kaggle.com/amandam1/breastcancerdataset and interpreted this dataset based on the form of BC, age, sex, tumor stages, surgery type, and survival rate. Among the 334 patients, 70% were diagnosed with infiltrating ductal carcinoma, 27% with infiltrating lobular carcinoma, and 3% with mucinous carcinoma. Overall, out of 334 BC patients: 64 (19.16%) were in stage I, 189 (56.59%) in stage II, and 81 (24.25%) in stage III. Sixty-six, 67, 96, and 105 patients underwent lumpectomy, simple mastectomy, modified radical mastectomy, and other types of surgery, respectively. The survival rates were 83.4% for stage I, 79.1% for stage II, and 77% for stage III. Findings from the present study demonstrated that ML provides an important tool to curate large amount of BC data, as well as a scientific means to improve BC outcomes.

Three-dimensional properties of the viscous boundary layer in turbulent Rayleigh–Bénard convection

We report an experimental study of the viscous boundary layer (BL) properties of turbulent Rayleigh–Bénard convection in a cylindrical cell. The velocity profile with all three components was measured from the centre of the bottom plate by an integrated home-made particle image velocimetry system. The Rayleigh number $Ra$ varied in the range $1.82 \times 10^8 \le Ra \le 5.26 \times 10^9$ and the Prandtl number $Pr$ was fixed at $Pr = 4.34$ . The probability density function of the wall-shear stress indicates that using the velocity component in the mean large-scale circulation (LSC) plane alone may not be sufficient to characterise the viscous BL. Based on a dynamic wall-shear frame, we propose a method to reconstruct the measured full velocity profile which eliminates the effects of complex dynamics of the LSC. Various BL properties including the eddy viscosity are then obtained and analysed. It is found that, in the dynamic wall-shear frame, the eddy viscosity profiles along the centre line of the convection cell at different $Ra$ all collapse on a single master curve described by $\nu _t^d / \nu = 0.81 (z / \delta _u^d) ^{3.10 \pm 0.05}$ . The Rayleigh number dependencies of several BL quantities are also determined in the dynamic frame, including the BL thickness $\delta _u^d$ ( ${\sim } Ra^{-0.21}$ ), the Reynolds number $Re^d$ ( ${\sim }Ra^{-0.46}$ ) and the shear Reynolds number $Re_s^d$ ( ${\sim } Ra^{0.24}$ ). Within the experimental uncertainty, these scaling exponents are the same as those obtained in the static laboratory frame. Finally, with the measured full velocity profile, we obtain the energy dissipation rate at the centre of the bottom plate $\varepsilon _{w}$ , which is found to follow $\langle \varepsilon _{w} \rangle _t \sim Ra^{1.25}$ .

The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix.

Usual interstitial pneumonia (UIP) is a histological pattern characteristic of idiopathic pulmonary fibrosis (IPF). The UIP pattern is patchy with histologically normal lung adjacent to dense fibrotic tissue. At this interface, fibroblastic foci (FF) are present and are sites where myofibroblasts and extracellular matrix (ECM) accumulate. Utilizing laser capture microdissection-coupled mass spectrometry, we interrogated the FF, adjacent mature scar, and adjacent alveoli in 6 fibrotic (UIP/IPF) specimens plus 6 nonfibrotic alveolar specimens as controls. The data were subjected to qualitative and quantitative analysis and histologically validated. We found that the fibrotic alveoli protein signature is defined by immune deregulation as the strongest category. The fibrotic mature scar classified as end-stage fibrosis whereas the FF contained an overabundance of a distinctive ECM compared with the nonfibrotic control. Furthermore, FF were positive for both TGFB1 and TGFB3, whereas the aberrant basaloid cell lining of FF was predominantly positive for TGFB2. In conclusion, spatial proteomics demonstrated distinct protein compositions in the histologically defined regions of UIP/IPF tissue. These data revealed that FF are the main site of collagen biosynthesis and that the adjacent alveoli are abnormal. This essential information will inform future mechanistic studies on fibrosis progression.

Human Umbilical Cord Lining-Derived Epithelial Cells: A Potential Source of Non-Native Epithelial Cells That Accelerate Healing in a Porcine Cutaneous Wound Model.

Human umbilical cord lining epithelial cells [CLECs) are naïve in nature and can be ethically recovered from cords that are routinely discarded. The success of using oral mucosal epithelial cells for cornea defects hints at the feasibility of treating cutaneous wounds using non-native CLECs. Herein, we characterized CLECs using flow cytometry (FC) and skin organotypic cultures in direct comparison with skin keratinocytes (KCs). This was followed by wound healing study to compare the effects of CLEC application and the traditional use of human skin allografts (HSGs) in a porcine wound model. While CLECs were found to express all the epidermal cell markers probed, the major difference between CLECs and KCs lies in the level of expression (in FC analysis) as well as in the location of expression (of the epithelium in organotypic cultures) of some of the basal cell markers probed. On the pig wounds, CLEC application promoted accelerated healing with no adverse reaction compared to HSG use. Though CLECs, like HSGs, elicited high levels of local and systemic immune responses in the animals during the first week, these effects were tapered off more quickly in the CLEC-treated group. Overall, the in vivo porcine data point to the potential of CLECs as a non-native and safe source of cells to treat cutaneous wounds.

Investigation of CDH1 germline mutations in Turkish patients with Kaposi’s sarcoma

Abstract Objectives Kaposi’s sarcoma (KS) develops from the lining cells of blood or lymphatic vessels and may appear as red, purple, brown, or black lesions. E-cadherin, CDH1, is a cell adhesion molecule located on the surface of epithelial cells. CDH1 gene expression is downregulated in several cancers and is considered a tumor suppressor gene involved in epithelial-mesenchymal transition in carcinomas. Loss of CDH1 gene expression is observed in many carcinomas, mainly diffuse gastric carcinomas and lobular breast carcinomas, as well as skin tumors. This study investigates the CDH1 germline mutations in HIV-negative (Human Immunodeficiency) Virus KS patients in the Turkish population. Methods The study examined 25 peripheral blood mononuclear cells from KS patients using the Sanger sequencing technique. Results Sixteen exons of the CDH1 gene were sequenced, and a pathogenic functional germline mutation, HET c.2245C &gt; T, p.(Arg749Trp) rs776975632, NM _004360.5, was identified in a patient with a family history of gastric and breast cancer with a high number of lesions compared to other KS patients. Discussion: KS patients with a family history of cancer could be screened for CDH1 gene and cancer-related-gen variants in the future. Conclusions KS is a rare malignancy, and genetic analysis will benefit KS patients. Further studies are needed to describe better the variations detected in a large number of KS patients in this study.

Reactivation of Bone Lining Cells are Attenuated Over Repeated Anti-sclerostin Antibody Administration.

Reactivation of bone lining cells (BLCs) is a crucial mechanism governing the anabolic action of anti-sclerostin antibody (Scl-Ab) via modeling-based bone formation; however, it remains unclear whether this reactivation can be attenuated after persistent administration of Scl-Ab. Here, we aimed to investigate the reproducibility of persistent Scl-Ab administration for the reactivation of BLCs, and to elucidate the relationship between the activity of BLCs and serum levels of N-terminal procollagen type I (P1NP) during chronic Scl-Ab administration. We conducted an osteoblast lineage tracing study. Briefly, Dmp1-CreERt2(+):Rosa26R mice were injected with 1mg of 4-hydroxy-tamoxifen weekly from postnatal weeks four to eight. Mice were treated twice with either vehicle or Scl-Ab (25mg/kg) at weeks 12, 16, and 20, and were euthanized at weeks 8, 12, 13, 16, 17, 20, and 21 (4-6 mice in each group). After euthanization, the number and thickness of X-gal (+) cells on the periosteum of the femoral bones and the serum levels of P1NP were quantified at each time point. Scl-Ab induced a significant increase in the thickness of X-gal (+) cells on periosteal bone surfaces at postnatal weeks 13 (after 1st dose), 17 (after 2nd dose), and 21 (after 3rd dose) compared to that in vehicle-treated mice (all P < 0.001). In the Scl-Ab group, significant increases in the thickness of labeled cells were observed between weeks 16 and 17 and weeks 20 and 21 (both P < 0.001). The percentage increase in X-gal (+) cell thickness was 108.9% from week 12 to week 13, 54.6% from week 16 to week 17, and 49.2% from week 20 to week 21 in the Scl-Ab group. Although Scl-Ab treatment increased the serum levels of P1NP at postnatal weeks 13 and 17 compared with those at week 12 (P = 0.017 and P = 0.038, respectively), the same was not observed at week 21 (P = 0.296). A significant increase in P1NP levels was observed between weeks 16 and 17 and weeks 20 and 21 in the Scl-Ab group (P = 0.005 and P = 0.007, respectively). The percentage increase in P1NP levels was 141.7% from weeks 12 to 13, 114.8% from weeks 16 to 17, and 99.4% from weeks 20 to 21. Serum P1NP levels were positively correlated with X-gal (+) cell thickness (R2 = 0.732, P < 0.001). Reactivation of BLCs is modestly attenuated, but reproducible, during persistent Scl-Ab administration. Serum P1NP levels appear to be an indicator of the impact of Scl-Ab on the conversion of BLCs into mature osteoblasts on periosteal bone surfaces, thus contributing to modeling-based bone formation.

Papillary renal cell neoplasm with reverse polarity: A new subtype of renal tumour with favorable prognosis

IntroductionPapillary renal cell neoplasm with reverse polarity (PRNRP) has recently been recognized as an entity separate from the traditional classification of papillary renal cell carcinomas, due to its specific histopathological, immunophenotypic and molecular characteristics, as well as its indolent behavior. Material and methodsWe provide 6 new cases and a review of the literature published until the present time, which comprises a total number of 104 cases. ResultsOur PRNRP cases correspond to 5 men and one woman aged between 47 and 91 years. In 5 of the 6 cases, the PRNRP was an incidental finding in nephrectomy specimens. Nephrectomy had been indicated due to the presence of another renal tumor, except for one case, in which surgical intervention was indicated due to PRNRP. Our cases present mass sizes between 2 and 13 mm, as well as papillary histology with a monolayered lining of eosinophilic cells with low-grade nuclei in apical location. Immunohistochemically, they show a constant positivity for GATA3 and negativity for vimentin. KRAS mutations were identified in 50% of our cases. After a follow-up ranging between one and 60 months, 5 of the cases were still alive without recurrences or metastases, and one died from urothelial carcinoma. ConclusionsOur cases agree with the clinical and pathological characteristics described in the PRNRP cases published to date. With the present study, we provide the first series of national cases corroborating the existence of well-defined and constant diagnostic criteria that allow PRNRP to be considered as a distinctive entity.

PGC-1 alpha regulates mitochondrial biogenesis to ameliorate hypoxia-inhibited cementoblast mineralization.

Hypoxia often occurs in inflammatory tissues, such as tissues affected by periodontitis and apical periodontitis lesions. Mitochondrial biogenesis can be disrupted in hypoxia. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a core factor required for mitochondrial biogenesis. Cementoblasts are root surface lining cells that play an integral role in cementum formation. There is a dearth of research on the effect of hypoxia on cementoblasts and underlying mechanisms, particularly in relation to mitochondrial biogenesis during the hypoxic process. In this study, we found that the expression of hypoxia inducible factor-1α was elevated in apical periodontitis tissues in vivo. In contrast, periapical lesions exhibited a reduction of PGC-1α expression. For in vitro experiments, cobalt chloride (CoCl2 ) was used to induce hypoxia. We observed that CoCl2 -induced hypoxia suppressed the mineralization ability and mitochondrial biogenesis of cementoblasts, accompanied by abnormal mitochondria morphology. Furthermore, we found that CoCl2 blocked the p38 pathway, while it activated the Erk1/2 pathway, with the former upregulating the expression of PGC-1α, while the latter reversed the effects. Overall, our findings demonstrate that mitochondrial biogenesis, especially via PGC-1α, is impaired during cementogenesis in the context of CoCl2 -induced hypoxia, dependent on the mitogen-activated protein kinase signaling pathway.

Anatomical, Histological and Radiological Studies of Parotid Salivary Glands of the Red Fox (Vulpes vulpes) with Comparison to Baladi Dog

The present study was designed to investigate and compare the gross anatomy and histology of the parotid glands, with details of their ducts and radicals, in dogs and foxes, using contrast radiographs. It was applied on six heads for each apparently healthy, adult Baladi dog and red fox that was euthanatized by pentobarbital. All parotid salivary glands were dissected for morphological investigations. Two specimens were injected through the parotid papilla by colored latex neoprene to show the intra glandular distribution of the parotid duct and the other one was inoculated by Urographin for lateral radiograph. The parotid salivary gland appeared as a thin, unevenly triangular shaped gland, located ventrally to the base of the ear. Dorsal border of the gland was notched in the dog but not in the red fox. The parotid radicals had four main branches in the dog, while three major radicals were seen in red fox. Portions of the right and left lobes of parotid salivary glands from other three heads for each dog and fox were fixed in 10% neutral buffered formalin for histological and histochemical investigation. The parotid gland of the dog consisted of pure serous acini, while it consisted of both serous and mucous secretory units in the fox. The acinar cells in the dog revealed a weak positive reaction to the Alcian blue stain. On the contrary, acinar cells in the fox were particularly mucous adenomeres, displaying a significantly high positive reaction. Both secretory acinar cells and duct system lining cells in the dog and fox parotid gland showed weak positive reaction to Periodic Acid-Schiff stain. This work gave a detailed description of parotid salivary gland to help veterinarians in clinical diagnosis and surgical approach.

Growth Performance, Histological Changes and Functional Tests of Broiler Chickens Fed Diets Supplemented with Tribulus Terrestris Powder.

The current experiment aimed to investigate the effects of TT powder on performance parameters and functional tests, as well as on morphological and histological changes in the liver, kidney and ileum in broiler chickens. Commercial broilers (total = 168 females) were used, equally divided into three dietary treatments (C = 0.0, T1 = 0.75, and T2 = 1.5 g/kg diet). The growth performance (1-35 days of age), absolute and relative weight, liver and kidney functional tests, intestinal morphology (14 and 35 days of age), and histomorphology of the ileum (35 days of age) were evaluated. At 35 days of age, histopathological changes in the ileum, liver, and kidney were also examined. The results showed that the growth performance and absolute and relative weights of the liver and kidney had no negative effects when dietary supplementation with TT powder was given at 0.75 g/kg diet (T1), whereas a decrease was observed at T2 (p &lt; 0.05). Liver and kidney functional tests showed no significant effects in all feed treatments (14 days), while T1 showed lower (p &lt; 0.05) ALT and AST levels (35 days). T1 exhibited higher weights, lengths, and weight-to-length ratios of the small intestine, and relative lengths of the duodenum (p &lt; 0.05). Histomorphometric measurements of the ileum were higher (p &lt; 0.05) in chickens fed the 0.75 g TT/kg diet, and except for in the goblet cell count and epithelial thickness, there were no differences between treatments (p &gt; 0.05). In T1, hepatocytes were more normal but hepatic sinusoids were dilated, whereas in T2, lymphocytes had infiltrated around the central vein and lining endothelial cells had been lost. The kidney was improved in T1 and T2 compared with the control group. Ileal villi were shorter in T2, and some villi fused with enterocyte necrosis and inflammatory cells accumulated in the lumen. We concluded that TT powder (0.75 g/kg feed) has a safe effect and is healthy for broilers.

Transduction characteristics of alternative adeno-associated virus serotypes in the cat brain by intracisternal delivery

Multiple studies have examined the transduction characteristics of different AAV serotypes in the mouse brain, where they can exhibit significantly different patterns of transduction. The pattern of transduction also varies with the route of administration. Much less information exists for the transduction characteristics in large-brained animals. Large animal models have brains that are closer in size and organization to the human brain, such as being gyrencephalic compared to the lissencephalic rodent brains, pathway organization, and certain electrophysiologic properties. Large animal models are used as translational intermediates to develop gene therapies to treat human diseases. Various AAV serotypes and routes of delivery have been used to study the correction of pathology in the brain in lysosomal storage diseases. In this study, we evaluated the ability of selected AAV serotypes to transduce cells in the cat brain when delivered into the cerebrospinal fluid via the cisterna magna. We previously showed that AAV1 transduced significantly greater numbers of cells than AAV9 in the cat brain by this route. In the present study, we evaluated serotypes closely related to AAVs 1 and 9 (AAVs 6, AS, hu32) that may mediate more extensive transduction, as well as AAVs 4 and 5, which primarily transduce choroid plexus epithelial (CPE) and ependymal lining cells in the rodent brain. The related serotypes tended to have similar patterns of transduction but were divergent in some specific brain structures.

An in silico model for woven bone adaptation to heavy loading conditions in murine tibia.

Existing in silico models for lamellar bone adaptation to mechanical loading are unsuitable for predicting woven bone growth. This anomaly is due to the difference in mechanobiology of the woven bone with respect to that of the lamellar bone. The present study is aimed at developing an in silico bone-adaptation model for woven bone at cellular and tissue levels. The diffusion of Ca2+ ions reaching lining cells from the osteocytic network and the bone cortex in response to a mechanical loading on the cortical bone has been considered as a stimulus. The diffusion of ions within osteocytic network has been computed with a lacunar-canalicular network (LCN) in which bone cells are uniformly arranged. Strain energy density is assumed to regulate ion flow within the network when the induced normal strain is above a threshold level. If the induced strain exceeds another higher threshold level, then the strain with a power constant is additionally assumed to regulate the stimulus. The intracellular flow of Ca2+ ions within the LCN has been simulated using Fick's laws of diffusion, using a finite element method. The ion diffusion from bone cortex to vesicles has been formulated as a normal strain with a power constant. The stimuli reaching the surface cells are assumed to form the new bone. The mathematical model closely predicts woven bone growth in mouse and rat tibia for various in vivo loading conditions. This model is the first to predict woven bone growth at tissue and cellular levels in response to heavy mechanical loading.