Stomach engineering: region-specific characterization of the decellularized porcine stomach.

PURPOSE: Patients affected by microgastria, severe gastroesophageal reflux, or those who have undergone subtotal gastrectomy, have commonly described reporting dumping syndromes or other symptoms that seriously impair the quality of their life. Gastric tissue engineering may offer an alternative approach to treating these pathologies. Decellularization protocols have great potential to generate novel biomaterials for large gastric defect repair. There is an urgency to define more reliable protocols to foster clinical applications of tissue-engineered decellularized gastric grafts. METHODS: In this work, we investigated the biochemical and mechanical properties of decellularized porcine stomach tissue compared to its native counterpart. Histological and immunofluorescence analyses were performed to screen the quality of decellularized samples. Quantitative analysis was also performed to assess extracellular matrix composition. At last, we investigated the mechanical properties and cytocompatibility of the decellularized tissue compared to the native. RESULTS: The optimized decellularization protocol produced efficient cell removal, highlighted in the absence of native cellular nuclei. Decellularized scaffolds preserved collagen and elastin contents, with partial loss of sulfated glycosaminoglycans. Decellularized gastric tissue revealed increased elastic modulus and strain at break during mechanical tensile tests, while ultimate tensile strength was significantly reduced. HepG2 cells were seeded on the ECM, revealing matrix cytocompatibility and the ability to support cell proliferation. CONCLUSION: Our work reports the successful generation of acellular porcine gastric tissue able to support cell viability and proliferation of human cells.

Serum C-terminal telopeptide of Type-I collagen (CTx) concentration and myocardial hyperechogenicity in cats with hypertrophic cardiomyopathy.

Objective: This study sought to determine the serum concentrations of C-terminal telopeptide of Type-I collagen (CTx), a marker of collagen degradation, in a hospital population of cats with hypertrophic cardiomyopathy (HCM). The study also evaluated the prevalence of myocardial hyperechogenicity of the left ventricle (LV) in the same cats. Animals and procedure: Cats brought to a university veterinary cardiology service entered the study when they had an echocardiographic diagnosis of HCM; echocardiographically normal cats served as controls. Serum CTx concentrations were assessed using ELISA. Results: There was no difference in serum CTx concentrations between cats with HCM and controls (HCM: median 0.248 ng/mL, controls: median 0.253 ng/mL; P = 0.4). Significantly more cats with HCM (60%) showed echocardiographic LV myocardial hyperechogenicity compared to normal controls (17%; P = 0.0057), but serum CTx concentrations were not different between these 2 groups. Conclusion and clinical relevance: These results indicate that, as in human patients with HCM and in contrast to earlier feline studies, there was no evidence of enhanced collagen degradation indicated by serum CTx concentrations in cats with HCM compared to normal controls.

Concentration sérique de télopeptide C-terminal du collagène de Type I (CTx) et hyperéchogénicité myocardique chez des chats atteints de cardiomyopathie hypertrophique. Objectif: Le premier objectif de cette étude était d'évaluer le taux sérique d'un marqueur de dégradation de collagène, soit le télopeptide C-terminal du collagène de Type-I (CTx), chez les chats atteints de cardiomyopathie hypertrophique (CMH). Le deuxième objectif était d'évaluer la prévalence de l'hyperéchogénicité du myocarde du ventricule gauche chez ces mêmes chats. Animaux et procédures: Les chats participant à l'étude avaient été présentés pour soins à un service de cardiologie vétérinaire universitaire, et ces chats avaient un diagnostic échocardiographique soit de CMH, soit d'aucune lésion cardiaque (groupe témoin). Le taux sérique de CTx a été évalué de façon immuno-enzymatique par ELISA. Résultats: Les résultats n'ont démontré aucune différence entre le taux sérique de CTx chez les chats atteint de CMH et le taux sérique de CTx chez les chats sans lésion cardiaque (CMH : médiane, 0,248 ng/mL; groupe témoin : médiane, 0,253 ng/mL; P = 0,4). Plus de chats atteints de CMH (60 %) que de chats dans le groupe témoin (17 %) ont démontré une hyperéchogénicité du myocarde du ventricule gauche à l'échocardiographie (P = 0,0057), quoique les taux sériques de CTx n'étaient pas différents entre ces 2 groupes. Conclusion et signification clinique: Ces résultats n'indiquent aucune augmentation de la dégradation de collagène chez les chats atteints de CMH, ce qui s'apparente aux résultats provenant d'études antérieures de la CMH chez l'humain mais non pas à ceux provenant d'études de la CMH féline.(Traduit par les auteurs).

VANL-100 Attenuates Beta-Amyloid-Induced Toxicity in SH-SY5Y Cells.

Antioxidants are being explored as novel therapeutics for the treatment of neurodegenerative diseases such as Alzheimer's disease (AD) through strategies such as chemically linking antioxidants to synthesize novel co-drugs. The main objective of this study was to assess the cytoprotective effects of the novel antioxidant compound VANL-100 in a cellular model of beta-amyloid (Aß)-induced toxicity. The cytotoxic effects of Aß in the presence and absence of all antioxidant compounds were measured using the 3-(4,5-dimethylthiazol-2-yl)2-5-diphenyl-2H-tetrazolium bromide (MTT) assay in SH-SY5Y cells in both pre-treatment and co-treatment experiments. In pre-treatment experiments, VANL-100, or one of its parent compounds, naringenin (NAR), alpha-lipoic acid (ALA), or naringenin + alpha-lipoic acid (NAR + ALA), was administrated 24 h prior to an additional 24-h incubation with 20 µM non-fibril or fibril Aß25-35. Co-treatment experiments consisted of simultaneous treatment with Aß and antioxidants. Pre-treatment and co-treatment with VANL-100 significantly attenuated Aß-induced cell death. There were no significant differences between the protective effects of VANL-100, NAR, ALA, and NAR + ALA with either form of Aß, or in the effect of VANL-100 between 24-h pre-treatment and co-treatment. These results demonstrate that the novel co-drug VANL-100 is capable of eliciting cytoprotective effects against Aß-induced toxicity.

Influence of staple line number and configuration on the leakage of small intestinal functional end-to-end stapled anastomosis: An ex vivo study.

OBJECTIVE: To determine the influence of the staple line configuration on the leakage of small intestinal functional end-to-end stapled anastomosis (FEESA). STUDY DESIGN: Experimental, ex vivo, randomized study. SAMPLE POPULATION: Jejunal segments (N = 72) from 10 mature, canine cadavers. METHODS: Jejunal segments (10 cm) were randomly assigned to a control group (8 segments) and 4 FEESA groups (16 segments/group (8 constructs/group)), according to the number of rows of staples used in the vertical (V) and transverse lines (T), respectively: Control, 2-row V/2-row T (2V/2T), 2-row V/3-row T (2V/3T), 3-row V/2-row T (3V/2T), 3-row V/3-row T (3V/3T). Initial leak pressure (ILP), maximum intraluminal pressure (MIP), and initial leakage location (ILL) were compared. RESULTS: The ILP (mean ± SD) for control segments, 2V/2T, 2V/3T, 3V/2T and 3V/3T were 321.38 ± 34.59, 32.88 ± 7.36, 50.13 ± 10.46, 34.38 ± 11.78, 69.88 ± 21.23 mmHg, respectively. All FEESAs initially leaked at lower pressures than intact segments. The only other differences detected between groups consisted of ILPs that were higher when FEESAs were closed with 3V/3T (69.88 ± 21.23 mmHg) than 2V/2T (32.88 ± 7.36, P < .001). Initial leakage occurred predominantly from the transverse staple line rather than the anastomotic crotch (P < .001). CONCLUSION: Placing 3 rows of staples in the transverse line (with or without a third row in the vertical staple line) improved resistance to leakage of FEESAs in normal cadaveric specimens. CLINICAL SIGNIFICANCE: The addition of a third row of staples in the transverse line (with or without a third row in the vertical staple line) in FEESAs should be further investigated as a strategy to reduce intestinal leakage clinically.

Evaluation of the performance of an endoscopic 3-mm electrothermal bipolar vessel sealing device intended for single use after multiple use-and-resterilization cycles.

OBJECTIVE: To evaluate the performance of an endoscopic 3-mm electrothermal bipolar vessel sealing device (EBVS) intended for single use after multiple use-and-resterilization cycles. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Eight 3-mm EBVS handpieces. METHODS: Handpieces were subjected to a maximum of 15 cycles of testing, including simulated surgery, sealing and burst pressure testing of porcine carotid arteries, reprocessing, and hydrogen peroxide plasma resterilization. Failure was defined as two sequential vascular seal leakage events occurring at <250 mm Hg. Histological evaluation, maximum external temperature of the jaws, sealing time, tissue adherence, jaw surface characterization, and mechanical deterioration were studied. Failure rate was analyzed by using a Kaplan-Meier curve. Linear and ordinal logistic mixed models were used to analyze sealing time, handpiece jaw temperature, and adherence score. RESULTS: Mean ± SD diameter of arteries was 3.22 ± 0.35 mm. Failure was observed starting at cycle 10 and going up to cycle 13 in 37.5% (3/8) of the handpieces. Tissue adherence increased after each cycle (P < .001). Maximum external temperature (79.8°C ± 13.9°C) and sealing time (1.8 ± 0.5 seconds) were not significantly different throughout cycles up to failure. A flatter surface and large scratches were observed microscopically throughout the jaw surface after repeated use and resterilization. CONCLUSION: The 3-mm EBVS handpiece evaluated in this study can be considered safe to use for up to nine reuse-and-resterilization cycles. CLINICAL SIGNIFICANCE: These data provide the basis for establishing preliminary guidelines for the reuse and hydrogen peroxide plasma resterilization of an endoscopic 3-mm EBVS handpiece.

A co-drug conjugate of naringenin and lipoic acid mediates neuroprotection in a rat model of oxidative stress.

Using our in vitro and in vivo models of oxidative stress, the current study was designed to determine the neuroprotective potential of naringenin, alone or in combination with lipoic acid. In our mixed neuronal culture exposed to hypoxia and subsequent reoxygenation, naringenin was shown to provide significant neuroprotection against cell death at a concentration of 2.5 µmol/L. Lipoic acid (LA) did not produce neuroprotection at any concentration tested (0.25-100 µmol/L). In contrast, when naringenin was covalently combined with LA, producing a novel compound named "VANL-100", significant neuroprotection was observed at a concentration as low as 2×10-2  µmol/L (100-fold more potent). An ELISA for antioxidant capacity demonstrated that naringenin and VANL-100 likely resulted in neuroprotection by increasing the free radical scavenging capacity of the neuronal cells. Pretreatment of rats with the above compounds prior to middle cerebral artery occlusion (MCAO) followed by reperfusion, showed similar results. Naringenin significantly reduced infarct volume at a dose of 10 mg/kg while VANL-100 produced significant neuroprotection at a dose as low as 1×10-4  mg/kg (10 000-fold more potent). This VANL-100-induced neuroprotection persisted even when administered 1 and 3 hours into the reperfusion time course. Taken together, these results suggest that our novel compound, VANL-100 is neuroprotective, likely via a mechanism that involves increasing the antioxidant capacity of neuronal cells. Our results also show that VANL-100 is 100-10 000-fold more potent than the parent compounds, which adds to the growing evidence in support of combination therapy targeting oxidative stress in neurodegenerative diseases.

A novel synthetic chemical entity (UPEI-800) is neuroprotective in vitro and in an in vivo rat model of oxidative stress.

In this study, we tested a novel synthetic pyrazole-containing compound, 5-amino-1-phenyl-1H-pyrazole-4-carbonitrile (APPC), as an antioxidant in both in vitro and in vivo models of oxidative stress. In addition, the utility of covalently combining APPC with another well-established antioxidant, lipoic acid (LA), was also tested in both models. The in vitro results demonstrated that pretreatment with APPC in a mixed neuronal-glial culture exposed to oxygen-glucose deprivation (OGD) followed by reoxygenation-refeeding, resulted in significant neuroprotection at concentrations between 2.5 to 25 µmol/L. In contrast, LA was not neuroprotective following OGD alone or following reoxygenation-refeeding. However, the synthetic covalent combination of APPC with LA, named "UPEI-800", resulted in significant neuroprotection at concentrations between 0.027 and 2.7 µmol/L (100-fold more potent than APPC alone), an effect shown to be correlated with increased cellular antioxidant capacity. Further, in an in vivo model of ischaemia-reperfusion injury following transient occlusion of the middle cerebral artery (tMCAO), both APPC (0.1 and 1.0 mg/kg) and UPEI-800 (1×10-3  mg/kg) provided significant neuroprotection. Consistent with the in vitro findings, the in vivo results following tMCAO also demonstrated a 100-fold increase in the potency of the covalently linked compound UPEI-800 compared to APPC alone.

Claudin-3 and claudin-5 protein folding and assembly into the tight junction are controlled by non-conserved residues in the transmembrane 3 (TM3) and extracellular loop 2 (ECL2) segments.

The mechanism of tight junction (TJ) assembly and the structure of claudins (Cldn) that form the TJ strands are unclear. This limits the molecular understanding of paracellular barriers and strategies for drug delivery across tissue barriers. Cldn3 and Cldn5 are both common in the blood-brain barrier but form TJ strands with different ultrastructures. To identify the molecular determinants of folding and assembly of these classic claudins, Cldn3/Cldn5 chimeric mutants were generated and analyzed by cellular reconstitution of TJ strands, live cell confocal imaging, and freeze-fracture electron microscopy. A comprehensive screening was performed on the basis of the rescue of mutants deficient for strand formation. Cldn3/Cldn5 residues in transmembrane segment 3, TM3 (Ala-127/Cys-128, Ser-136/Cys-137, Ser-138/Phe-139), and the transition of TM3 to extracellular loop 2, ECL2 (Thr-141/Ile-142) and ECL2 (Asn-148/Asp-149, Leu-150/Thr-151, Arg-157/Tyr-158), were identified to be involved in claudin folding and/or assembly. Blue native PAGE and FRET assays revealed 1% n-dodecyl ß-d-maltoside-resistant cis-dimerization for Cldn5 but not for Cldn3. This homophilic interaction was found to be stabilized by residues in TM3. The resulting subtype-specific cis-dimer is suggested to be a subunit of polymeric TJ strands and contributes to the specific ultrastructure of the TJ detected by freeze-fracture electron microscopy. In particular, the Cldn5-like exoplasmic face-associated and particle-type strands were found to be related to cis-dimerization. These results provide new insight into the mechanisms of paracellular barrier formation by demonstrating that defined non-conserved residues in TM3 and ECL2 of classic claudins contribute to the formation of TJ strands with differing ultrastructures.

Guanosine protects against reperfusion injury in rat brains after ischemic stroke.

After ischemic stroke, early thrombolytic therapy to reestablish tissue perfusion improves outcome but triggers a cascade of deleterious cellular and molecular events. Using a collaborative approach, our groups examined the effects of guanosine (Guo) in response to ischemic reperfusion injury in vitro and in vivo. In a transient middle cerebral artery occlusion (MCAO) in rats, Guo significantly reduced infarct volume in a dose-dependent manner when given systemically either immediately before or 30 min, but not 60 min, after the onset of the 5.5-hr reperfusion period. In a separate experiment, Guo significantly reduced infarct volume after 24 hr of reperfusion when administered 5 min before reperfusion. Western blot analysis did not reveal any significant changes either in endoplasmic reticulum (ER) stress proteins (GRP 78 and 94) or HSP 70 or in levels of m-calpain. In vitro oxygen and glucose deprivation (OGD) significantly increased production of both reactive oxygen species (ROS) and interleukin-8 (IL-8) in the primary astrocytes. Guo did not alter ROS or IL-8 production when given to the astrocytes before OGD. However, Guo when added to the cells prior to or 30 min after reperfusion significantly reduced IL-8 release but not ROS formation. Our study revealed a dose- and time-dependent protective effect of Guo on reperfusion injury in vitro and vivo. The mechanisms by which Guo exerts its effect are independent of unfolded proteins in ER or the level of intracellular calcium or ROS formation. However, the effect may be induced, at least partially, by inhibiting IL-8, a marker of reperfusion-triggered proinflammatory events.

Characterization of serum and tissue oxytocinase and tissue oxytocin in the pregnant and non-pregnant mare.

Oxytocin is a hormone with functions in: reproduction, maternal bonding, milk ejection, and feeding/social behavior, and is reported to be present in a variety of tissues. Our goal is to characterize oxytocin and leucyl and cystinyl aminopeptidase (LNPEP/oxytocinase), a key regulator of oxytocin in mares. We measured serum and tissue LNPEP by ELISA from ovulation (D0) until D21-22 in non-pregnant (n = 5) and pregnant mares (n = 6); and in periparturient and postpartum mares (n = 18). Placenta (n = 7) and homogenized tissue of diestrus mares (n = 6) were evaluated using protein determinations and LNPEP ELISAs. Identification of LNPEP and OXT protein in tissues was also performed via western blot, immunohistochemistry and liquid chromatography-mass spectrometry (LC-MS/MS). Furthermore, in situ hybridization was performed for LNPEP and OXT on endometrium, myometrium, pituitary and corpus luteum (CL). Serum LNPEP concentration were similar. Placental LNPEP U/mg protein was highest in the body and pregnant horn. The highest to lowest LNPEP U/mg protein by tissue were: myometrium > follicle wall > endometrium > kidney > CL > liver. Oxytocin was identified in the equine pituitary, CL and placenta and is likely to act in autocrine or paracrine manner, while LNPEP may act systemically and locally to regulate the availability of OXT.

Lung viral infection modelling in a bioengineered whole-organ.

Lung infections are one of the leading causes of death worldwide, and this situation has been exacerbated by the emergence of COVID-19. Pre-clinical modelling of viral infections has relied on cell cultures that lack 3D structure and the context of lung extracellular matrices. Here, we propose a bioreactor-based, whole-organ lung model of viral infection. The bioreactor takes advantage of an automated system to achieve efficient decellularization of a whole rat lung, and recellularization of the scaffold using primary human bronchial cells. Automatization allowed for the dynamic culture of airway epithelial cells in a breathing-mimicking setup that led to an even distribution of lung epithelial cells throughout the distal regions. In the sealed bioreactor system, we demonstrate proof-of-concept for viral infection within the epithelialized lung by infecting primary human airway epithelial cells and subsequently injecting neutrophils. Moreover, to assess the possibility of drug screening in this model, we demonstrate the efficacy of the broad-spectrum antiviral remdesivir. This whole-organ scale lung infection model represents a step towards modelling viral infection of human cells in a 3D context, providing a powerful tool to investigate the mechanisms of the early stages of pathogenic infections and the development of effective treatment strategies for respiratory diseases.

UPEI-100, a conjugate of lipoic acid and apocynin, mediates neuroprotection in a rat model of ischemia/reperfusion.

Previous work in our laboratory has provided evidence that preadministration of apocynin and lipoic acid at subthreshold levels for neuroprotection enhanced the neuroprotective capacity when injected in combination. Therefore, the present investigation was designed to determine whether a co-drug consisting of lipoic acid and apocynin functional groups bound by a covalent bond, named UPEI-100, is capable of similar efficacy using a rodent model of stroke. Male rats were anesthetized with Inactin (100 mg/kg iv), and the middle cerebral artery was occluded for 6 h or allowed to reperfuse for 5.5 h following a 30-min occlusion (ischemia/reperfusion, I/R). Preadministration of UPEI-100 dose-dependently decreased infarct volume in the I/R model (P < 0.05), but not in the middle cerebral artery occlusion model of stroke. Using the optimal dose, we then injected UPEI-100 during the stroke or at several time points during reperfusion, and significant neuroprotection was observed when UPEI-100 was administered up to 90 min following the start of reperfusion (P < 0.05). A time course for this neuroprotective effect showed that UPEI-100 resulted in a decrease in infarct volume following 2 h of reperfusion compared with vehicle. The time course of this neuroprotective effect was also used to study several mediators along the antioxidant pathway and showed that UPEI-100 increased the level of mitochondrial superoxide dismutase and oxidized glutathione and decreased a marker of lipid peroxidation due to oxidative stress (HNE-His adduct formation). Taken together, the data suggest that UPEI-100 may utilize similar pathways to those observed for the two parent compounds; however, it may also act through a different mechanism of action.

Liuwei dihuang lowers body weight and improves insulin and leptin sensitivity in obese rats.

The present study was aimed at investigating the efficacy and mechanism(s) of action of a Chinese herbal formulation, Liuwei Dihuang (LWDH), as a prospective natural weight-lowering product. Following a 2-week acclimation period, 48 obesity-prone (OP-CD) rats were divided into 4 groups (n = 12 each). One group served as a positive control for obesity (OP), while the other 3 were challenged twice daily by oral gavage with total daily dosages of 500, 1500, or 3500 mg/kg BW LWDH, respectively, for 10 weeks. One group (n = 12) of obesity-resistant (OR-CD) rats served as the normal control group. All rats were fed the same AIN-93G diet modified to contain 60% energy from fat. The highest LWDH dose significantly reduced body weight during the last 4 weeks of treatment. Food intake was reduced beginning in week 2. The high LWDH dose lowered serum triglyceride (TG) and nonesterified fatty acid (NEFA) levels and body fat. Both the high and medium doses also lowered serum leptin and insulin levels. Liver function testing revealed no adverse side effects under the current experimental conditions. The results of the present study suggest that LWDH has potential as a preventive or therapeutic natural product against overweight and obesity.

Naturally Occurring Antioxidant Therapy in Alzheimer's Disease.

It is estimated that the prevalence rate of Alzheimer's disease (AD) will double by the year 2040. Although currently available treatments help with symptom management, they do not prevent, delay the progression of, or cure the disease. Interestingly, a shared characteristic of AD and other neurodegenerative diseases and disorders is oxidative stress. Despite profound evidence supporting the role of oxidative stress in the pathogenesis and progression of AD, none of the currently available treatment options address oxidative stress. Recently, attention has been placed on the use of antioxidants to mitigate the effects of oxidative stress in the central nervous system. In preclinical studies utilizing cellular and animal models, natural antioxidants showed therapeutic promise when administered alone or in combination with other compounds. More recently, the concept of combination antioxidant therapy has been explored as a novel approach to preventing and treating neurodegenerative conditions that present with oxidative stress as a contributing factor. In this review, the relationship between oxidative stress and AD pathology and the neuroprotective role of natural antioxidants from natural sources are discussed. Additionally, the therapeutic potential of natural antioxidants as preventatives and/or treatment for AD is examined, with special attention paid to natural antioxidant combinations and conjugates that are currently being investigated in human clinical trials.

Hemorrhagic Resuscitation Guided by Viscoelastography in Far-Forward Combat and Austere Civilian Environments: Goal-Directed Whole-Blood and Blood-Component Therapy Far from the Trauma Center.

Modern approaches to resuscitation seek to bring patient interventions as close as possible to the initial trauma. In recent decades, fresh or cold-stored whole blood has gained widespread support in multiple settings as the best first agent in resuscitation after massive blood loss. However, whole blood is not a panacea, and while current guidelines promote continued resuscitation with fixed ratios of blood products, the debate about the optimal resuscitation strategy-especially in austere or challenging environments-is by no means settled. In this narrative review, we give a brief history of military resuscitation and how whole blood became the mainstay of initial resuscitation. We then outline the principles of viscoelastic hemostatic assays as well as their adoption for providing goal-directed blood-component therapy in trauma centers. After summarizing the nascent research on the strengths and limitations of viscoelastic platforms in challenging environmental conditions, we conclude with our vision of how these platforms can be deployed in far-forward combat and austere civilian environments to maximize survival.

CYP17, catechol-o-methyltransferase, and glutathione transferase M1 genetic polymorphisms, lifestyle factors, and breast cancer risk in women on Prince Edward Island.

Genetic polymorphisms in enzymes controlling the formation and disposition of estrogens and their metabolites have been shown to influence breast cancer risk. Environmental and lifestyle factors may interact with estrogen metabolism polymorphisms to influence breast cancer risk. We studied the role of lifestyle factors and genetic polymorphisms in estrogen metabolism in women from Prince Edward Island (PEI), a small province of 135,000 people on the east coast of Canada. Women (207 cases; 621 controls) were matched on age, menopausal status, and family history of breast cancer. The predominant lifestyle risk factors previously reported to influence breast cancer risk such as body mass index (BMI), parity, and smoking had similar influences in the PEI population. Genetic polymorphisms in CYP17, GSTM1, and catechol-O-methyltransferase (COMT) were not associated with a general increase in breast cancer risk. However, the CYP17 A2/A2 genotype was only observed in women with estrogen receptor (ER) positive breast cancer and not in ER negative breast cancer. The increased risk associated with elevated BMI was only observed in women homozygous for the CYP17 and COMT reference alleles. Similarly, the increased risk associated with extended use of oral contraceptives (≥ 15years), was only observed in women homozygous for the reference alleles of CYP17 and COMT. The GSTM1 homozygous gene deletion was associated with a significantly increased risk of breast cancer in postmenopausal women with a family history of breast cancer risk. These results suggest the polymorphic genes that control estrogen formation and disposition interact significantly with other risk factors to influence breast cancer risk.

Recellularization of Native Tissue Derived Acellular Scaffolds with Mesenchymal Stem Cells.

The functionalization of decellularized scaffolds is still challenging because of the recellularization-related limitations, including the finding of the most optimal kind of cell(s) and the best way to control their distribution within the scaffolds to generate native mimicking tissues. That is why researchers have been encouraged to study stem cells, in particular, mesenchymal stem cells (MSCs), as alternative cells to repopulate and functionalize the scaffolds properly. MSCs could be obtained from various sources and have therapeutic effects on a wide range of inflammatory/degenerative diseases. Therefore, in this mini-review, we will discuss the benefits using of MSCs for recellularization, the factors affecting their efficiency, and the drawbacks that may need to be overcome to generate bioengineered transplantable organs.

Viscoelastic Testing and Coagulopathy of Traumatic Brain Injury.

A unique coagulopathy often manifests following traumatic brain injury, leading the clinician down a difficult decision path on appropriate prophylaxis and therapy. Conventional coagulation assays-such as prothrombin time, partial thromboplastin time, and international normalized ratio-have historically been utilized to assess hemostasis and guide treatment following traumatic brain injury. However, these plasma-based assays alone often lack the sensitivity to diagnose and adequately treat coagulopathy associated with traumatic brain injury. Here, we review the whole blood coagulation assays termed viscoelastic tests and their use in traumatic brain injury. Modified viscoelastic tests with platelet function assays have helped elucidate the underlying pathophysiology and guide clinical decisions in a goal-directed fashion. Platelet dysfunction appears to underlie most coagulopathies in this patient population, particularly at the adenosine diphosphate and/or arachidonic acid receptors. Future research will focus not only on the utility of viscoelastic tests in diagnosing coagulopathy in traumatic brain injury, but also on better defining the use of these tests as evidence-based and/or precision-based tools to improve patient outcomes.

Comparative study of three prostaglandin analogues in the treatment of newly diagnosed cases of ocular hypertension, open-angle and normal tension glaucoma.

BACKGROUND: To compare the efficacy and tolerance of three prostaglandin analogues, bimatoprost, latanoprost and travoprost in patients with previously untreated open-angle glaucoma and ocular hypertension. METHODS: Prospective randomized single (investigator) masked comparative clinical trial at the Taunton and Somerset NHS Hospital, Taunton, UK. Newly diagnosed, treatment naïve glaucoma/ocular hypertension patients were recruited. Patients were randomized into three groups to receive one of the three prostaglandin analogues. Intraocular pressure (IOP) was measured before starting treatment and after 2 and 6 months of treatment. The IOP reduction and the tolerance profile of each drug were compared. The data were analysed on the basis of intention to treat, using analysis of covariance comparing IOP in the three groups at 2 and 6 months, adjusting for baseline IOP. Tolerance levels were compared using Kruskal-Wallis test. RESULTS: Of the 122 patients, 40 patients were given bimatoprost, 42 received latanoprost and 40 had travoprost. At 2 months, there was a significant difference between the three treatment groups (P = 0.013) with bimatoprost achieving a greater reduction in IOP than the other two drops. However, at 6 months, the difference was not statistically significant (P = 0.13). There was no significant difference in the tolerance profile. CONCLUSION: All the three topical prostaglandin analogues are effective at lowering IOP, but bimatoprost was found to be most effective in the initial phase of the trial, and there was no statistically significant difference in the efficacy, among the three prostaglandin analogue eye drops after 6 months of treatment.

Decellularized extracellular matrix-rich hydrogel-silver nanoparticle mixture as a potential treatment for acute liver failure model.

Acute liver failure (ALF) occurs due to severe liver damage that triggers rapid loss of normal liver function. Here, we investigate the usefulness of an injectable liver extracellular matrix (LECM)-rich hydrogel generated from an optimized decellularization protocol incorporated with silver nanoparticles (AgNPs) as a promising therapy for ALF. First, we optimized a non-destructive protocol for rat liver decellularization to obtain ECM-rich well-preserved scaffold. Then, LECM hydrogel generated from two commonly used decellularization protocols were compared by LECM hydrogel obtained from our optimized protocol. The ALF model was induced by an intraperitoneal (IP) thioacetamide (TAA) injection followed by the IP injection of LECM hydrogel, collagen-AgNP mixture, or LECM hydrogel-AgNP mixture. LECM-rich scaffold and hydrogel were successfully obtained using our optimized decellularization protocol. Use of the LECM hydrogel-AgNP mixture to treat TAA-induced ALF greatly improved liver injury and histological liver regeneration. Interleukin-6 and transforming growth factor-beta expressions were significantly reduced, while albumin, hepatocyte growth factor, and Ki67-positive cells were highly expressed. Moreover, aspartate transaminase and alanine transaminase plasma levels and liver homogenate nitric oxide level were significantly lowered. In conclusion, the LECM hydrogel-AgNP mixture has potential efficient therapeutic and regenerative effects on TAA-induced liver injury.