Therapeutic effects of intermittent fasting on high-fat, high-fructose diet; involvement of jejunal aquaporin 1, 3, and 7.

Background: Aquaporins (AQPs) are transmembrane channel proteins. Aquaporin 1 (AQP1), Aquaporin 3 (AQP3), and Aquaporin 7 (AQP7) are expressed in the jejunum. The purpose of this study was to ascertain how a high-fat high-fructose diet (HFFD) and intermittent fasting (IF) affect AQP1, AQP3, and AQP7 expression in the rat jejunum. Methods: Sixteen adult male rats were divided into control rats (n = 4) fed on a basal diet and water ad libitum for 12 weeks; IF control rats (n = 4) followed the IF protocol, HFFD-fed rats (n = 8) fed HFFD for eight weeks, and rats were randomized into two groups: HFFD only or HFFD and IF protocol from the beginning of the 9th week until the end of the experiment. The lipid profile values were assessed after 12 weeks. Jejunal oxidative markers (malondialdehyde and reduced glutathione) and AQP1, AQP3, and AQP7 mRNA expression were measured. Jejunal sections were used for morphometric analysis of villus length and crypt depth. Immunohistochemical evaluation of AQP1, AQP3, and AQP7 expression was also performed. Results: IF ameliorates HFFD-induced lipid profile, oxidative stress, and jejunal morphometric changes. The results of both mRNA expression using PCR and immunohistochemistry showed a significant increase in AQP1, AQP3, and AQP7 expression in HFFD, whereas IF caused a decline in this expression. Conclusion: These findings suggest that IF can reduce inflammation, and oxidative stress and restore jejunal morphology caused by HFFD.

Evaluation of corneal backward light scattering in type 2 diabetes mellitus.

AIM: To compare the corneal backward light scattering values in type 2 diabetes mellitus (DM) patients with those of age and sex-matched healthy controls. METHODS: The study included 30 patients (30 eyes) with type 2 DM and 30 control subjects (30 eyes). Duration of diabetes, most recent hemoglobin A1c levels, along with the status of diabetic retinopathy, and existing medical treatment of all subjects were recorded. All subjects underwent a complete ophthalmologic examination. In addition, backward light scattering (densitometry) was measured to assess changes in corneal transparency using tomography (Pentacam HR). RESULTS: The type 2 DM patients included 12 males and 18 females and control subjects included 16 males and 14 females. The age was 50.40±7.80y (range: 40-68y) of the diabetic group and 49.30±9.50y (rang: 40-73y) of control group. The diabetic group demonstrated significantly higher mean densitometry values of the anterior (6-10 mm) zone (P=0.047), the total anterior layer (P=0.036) and the total cornea (P=0.043) than control group. The corneal densitometry of the diabetic eyes demonstrated no significant correlation with hemoglobin A1c levels and DM duration. CONCLUSION: Diabetic group has higher densitometry in anterior corneal (6-10 mm) zone, total anterior cornea, and total cornea and with no correlation with hemoglobin A1c levels and DM duration.

Gastric Myoelectric Activity and Body Composition Changes during Weight Loss via Sleeve Gastrectomy and Lifestyle Modification: Prospective Cohort Study.

The capability of bariatric surgery (BS) and lifestyle intervention (LSI) in ameliorating obesity-associated altered gastric myoelectric activity (GMA) in relation to body composition is underinvestigated. This work studied GMA during weight loss via sleeve gastrectomy and multimodal lifestyle intervention. Seventy-nine participants with morbid obesity were assigned into three groups: bariatric surgery (BS group, n = 27), in which laparoscopic sleeve gastrectomy was performed; lifestyle intervention (LS group, n = 22), in which a calorie-deficit balanced diet with gradual physical activity and personalized behavioral modification were carried out; and waitlist control (C group, n = 30). For all participants, multichannel electrogastrography (EGG) with water-load testing and bioelectric impedance body composition analysis were done at baseline, after three months, and at six months. In the BS group, the water-load volume was decreased but without improvement in the bradygastria. In the LS group, preprandial bradygastria were reduced and some postprandial normogastria were increased throughout the study period. Except for fat-free mass and total body water, the parameters of body composition changes were superior in the BS group. In the LS group, the amount of fat-mass loss was negatively correlated with bradygastria times and positively correlated with preprandial and the early postprandial average dominant frequency (ADF). In addition, in the BS group, fat-mass loss was positively correlated with the ADF at late postprandial times. In conclusion, compared to BS, LS produced moderate normalization of GMA with the preservation of fat-free mass. The GMA changes were significantly associated with the amount of fat loss, regardless of the method of obesity management.

Stem Cells in Bone Repair and Regeneration.

Bones normally function to provide both mechanical and locomotion supports in the body. They are highly specialized connective tissues that are characterized by mineralized extracellular components, which provide both rigidity and strength to bones. Stem cells hold great potentials for both the repair and regeneration of different tissue types, including bone tissues. The future use of stem cell therapy is promising for developing regenerative medicine approaches to treat disorders and diseases in a wide range of tissues such as cartilages and bones. Data have been accumulated recently on the application of different stem cell types in bone repair, regeneration, and disorders. In this article, we briefly describe the bone structure and review research progress and recently accumulated data on stem cell differentiation into osteoblasts as well as discuss the contributions of stem cell types to bone and cartilage repair, regeneration, and disease.

Association of Gastric Myoelectric Activity with Dietary Intakes, Substrate Utilization, and Energy Expenditure in Adults with Obesity.

Obesity can modulate gastric myoelectric activity (GMA); however, the relationship of GMA with nutrient intakes and substrate utilization in adults with obesity is lacking. We examined the association of dietary intakes, energy expenditure, and substrate utilization with the GMA. Participants (n = 115, 18−60 y) were divided into healthy weight (HW, n = 24), overweight (OW, n = 29), obese (OB, n = 41) and morbidly obese (MO, n = 21). Two-day multi-pass 24 h recalls were conducted. The GMA was measured by multichannel electrogastrography (EGG) with water-load (WL) testing. Resting metabolic rate (RMR) and percentages of substrate utilization were measured by indirect calorimetry. In the HW, protein intake was directly correlated with average dominant frequency (ADF) and with WL volume, while in obese participants and the MO subgroup, WL volume correlated with carbohydrate intake. In participants with obesity, ADF was positively correlated with fiber intake. In participants with obesity and the OB subgroup, RMR was positively correlated with water-load volume (r = 0.39 and 0.37, p < 0.05). The ADF showed negative correlations with percent of fat utilization and positive correlations with percent of CHO utilization in non-obese groups. However, protein utilization showed inverse correlation in all obese groups. In conclusion, these distinctive associations suggest that certain dietary compositions and dieting regimens impact GMA patterns.

Effect of seminal redox status on lipid peroxidation, apoptosis and DNA fragmentation in spermatozoa of infertile Saudi males.

OBJECTIVES: To assess the effect of seminal redox status on lipid peroxidation (LPO), apoptosis and integrity of sperm DNA in infertile males. Methods: In this case-control study, the total antioxidant status (TAS) and reactive oxygen species (ROS) levels were analyzed within the seminal plasma of fertile normozoospermic, n=40 and infertile (asthenozoospermic, n=30; oligoasthenoteratozoospermic, n=30) males. Additionally, the level of 4-hydroxynonenal (4-HNE), DNA fragmentation, and caspase-3 activity were estimated in the spermatozoa. RESULTS: Significantly (p less than 0.001) increased seminal ROS level with decreased TAS scores was observed in the infertile groups compared to normozoospermics. The infertile males showed marked elevated (p less than 0.001) levels of 4-HNE, DNA fragmentation and caspase-3 activity compared to normozoospermics, which was positively correlated to increased seminal ROS levels and negatively to the TAS score in the studied groups. Seminal ROS level was significantly inverse correlated to the semen parameters. Additionally, a strong negative correlation between DNA fragmentation, LPO, caspase-3activity and seminal parameters were observed. Conclusion: Seminal oxidative stress is a potential risk factor for LPO, DNA damage, and apoptosis in spermatozoa, which can affect semen quality and male fertility. Thus, in addition to conventional seminological parameters, measurement of seminal oxidative stress and sperm DNA integrity may also be employed to investigate the functional integrity of spermatozoa at the molecular level.

Metabolic Effects of Testosterone Hormone Therapy in Normal and Orchiectomized Male Rats: From Indirect Calorimetry to Lipolytic Enzymes.

BACKGROUND AND AIM: Changes in total energy expenditure (TEE) and substrate metabolism may help explain the metabolic actions of testosterone (T). This study measured respiratory quotient (RQ), TEE, ghrelin, insulin, and key lipolysis enzyme concentrations in relation to body weight (wt) and food intake (FI) in both normal and bilaterally orchiectomized rats with/without T treatment. METHODS: In total, thirty-two male Wistar rats (300-400 g) were divided into four groups (n = 8/group), including (a) sham-operated and vehicle-injected group (Sham), (b) T-treated sham group (T-Sham) for which sham-operated rats were injected with IM testosterone undecanoate (100 mg/kg, for one week), (c) orchiectomy and vehicle-injected group (Orch), and (d) T-replaced orchiectomy group (T-Orch). After one week, FI and wt were automatically recorded, indirect calorimetry parameters were measured, and blood samples were collected to measure T, ghrelin, insulin, growth hormone (GH), glucose, hormone-sensitive lipase (HSL), adipocyte triglyceride lipase (ATGL), free fatty acids (FFA), and lipid profiles. RESULTS: Orchiectomy decreased ghrelin, GH, and insulin levels, increased TEE and RQ, and lowered FI and wt. The T-Orch group exhibited increased levels of ghrelin (3-fold), insulin, GH, blood levels of lipolysis products, TEE, and FI in addition to reduced glucose levels (P < 0.05). This group demonstrated no significant changes in wt. In the T-Sham group, T increased ghrelin and insulin levels (P < 0.05) with strong positive correlations (r = 0.663 and 0.644, respectively, P < 0.05), increased ATGL levels, RQ toward carbohydrate utilization ranges, and TEE, and reduced HSL levels (P < 0.05) with insignificant changes in FI or wt. CONCLUSIONS: T administration in orchiectomized rats significantly increased orexigenic mediators such as ghrelin and insulin without inducing any significant changes in wt. The mechanism for this finding might be the increased TEE and the stimulation of lipolysis through the ATGL enzyme. The associated rise of GH might help in interference with accumulation of lipid in adipose tissue. Apart from the effect on GH, T-Sham showed similar effects of T supplementation.

Anterior lamina cribrosa surface depth in healthy Saudi females.

PURPOSE: This study was conducted to determine normative profile of anterior lamina cribrosa surface depth (ALCSD) in healthy Saudi females using Topcon Three-Dimensional (3D) Optical Coherence Tomography (OCT) 2000 - Spectral Domain (SD-OCT). In addition, the correlation between ALCSD and other clinical factors such as age, refractive error, intraocular pressure (IOP), central corneal thickness, anterior chamber depth, axial length, retinal nerve fiber layer thickness, and disk area was also assessed. DESIGN: This study was a prospective, nonrandomized, cross-sectional, observational, and quantitative study. METHODS: This study included 191 eyes of 191 healthy Saudi females from the College of Applied Medical Sciences of King Saud University. Stereoscopic disk photographs were reconstructed using Topcon 3D OCT-2000 for all subjects. ALCSD was measured at three planes (superior, middle, and inferior) and defined as the distance from Bruch's membrane opening level (reference line) to anterior lamina cribrosa surface. Average of ALCSD at all planes was defined as mean ALCSD of the eye. Correlation between ALCSD and all the clinical factors was performed by linear regression analysis. Paired t-test was performed in order to compare ALCSD at all planes. RESULTS: In this study, the average ALCSD was 371.88±114.62 µm (range, 155-647.6 µm). Paired t-test showed a significant difference between superior and middle planes (P=0.004) and middle and inferior planes (P=0.013). Using the same test, no significant difference between superior and inferior planes (P=0.820) was observed. Generally, the largest ALCSD was in the middle plane. In addition, linear regression analysis showed no significant correlation between ALCSD and associated clinical factors. CONCLUSION: This work is the first to provide the normative profile of ALCSD in Saudi females using Topcon 3D OCT-2000. Further studies are recommended for males, different ethnic populations, high myopic eyes, and different age groups using advanced imaging techniques such as enhanced depth imaging OCT.

Asymmetric cell division of stem cells in the lung and other systems.

New insights have been added to identification, behavior and cellular properties of embryonic and tissue-specific stem cells over the last few years. The modes of stem cell division, asymmetric vs. symmetric, are tightly regulated during development and regeneration. The proper choice of a stem cell to divide asymmetrically or symmetrically has great consequences for development and disease because inappropriate asymmetric division disrupts organ morphogenesis, whereas uncontrolled symmetric division induces tumorigenesis. Therefore, understanding the behavior of lung stem cells could identify innovative solutions for restoring normal morphogenesis and/or regeneration of different organs. In this concise review, we describe recent studies in our laboratory about the mode of division of lung epithelial stem cells. We also compare asymmetric cell division (ACD) in the lung stem cells with other tissues in different organisms.

Apoptosis and clinical severity in patients with psoriasis and HCV infection.

BACKGROUND: It has been proposed that hepatitis C virus (HCV) antigens are involved in the pathogenesis of psoriasis and may contribute to severity of the disease. Increased expression of the apoptosis-regulating proteins p53 and tTG and decreased levels of bcl-2 in the keratinocytes of the skin of psoriatic patients have been reported. AIM: This study aims to identify the serum levels of apoptosis-regulating proteins in patients with psoriasis and without HCV infection and to study the relation between clinical severity of psoriasis and the presence of HCV infection. MATERIALS AND METHODS: Disease severity was assessed by psoriasis area severity index score (PASI) of 90 patients with psoriasis grouped as mild (n = 30), moderate (n = 30) and severe (n = 30); 20 healthy individuals were used as controls. All groups were subjected for complete history taking, clinical examination, and tests for liver function and HCV infection. The serum levels of apoptosis related proteins: p53, tTG and bcl-2 were estimated by enzyme linked immune sorbent assay (ELISA). RESULTS: There was a statistically significant (P < 0.001) correlation between clinical severity of psoriasis and presence of HCV antibodies and HCV-mRNA. In addition, significantly (P < 0.001) raised serum p53 and tTG, and reduced bcl-2 were observed among HCV-positive patients as compared to HCV-negative patients and control patients. CONCLUSION: These results conclude that clinical severity of psoriasis is affected by the presence of HCV antibodies and overexpression of apoptotic related proteins. In addition, altered serum levels of apoptosis-regulating proteins could be useful prognostic markers and therapeutic targets of psoriatic disease.

Desmosomal adhesion in vivo.

Desmosomes are intercellular junctions that provide strong adhesion or hyper-adhesion in tissues. Here, we discuss the molecular and structural basis of this with particular reference to the desmosomal cadherins (DCs), their isoforms and evolution. We also assess the role of DCs as regulators of epithelial differentiation. New data on the role of desmosomes in development and human disease, especially wound healing and pemphigus, are briefly discussed, and the importance of regulation of the adhesiveness of desmosomes in tissue dynamics is considered.

Abrogation of Eya1/Six1 disrupts the saccular phase of lung morphogenesis and causes remodeling.

The Eya1 gene encodes a transcriptional co-activator that acts with Six1 to control the development of different organs. However, Six1-Eya1 interactions and functional roles in mesenchymal cell proliferation and differentiation as well as alveolarization during the saccular stage of lung development are still unknown. Herein, we provide the first evidence that Six1 and Eya1 act together to regulate mesenchymal development as well as alveolarization during the saccular phase of lung morphogenesis. Deletion of either or both Six1 and Eya1 genes results in a severe saccular phenotype, including defects of mesenchymal cell development and remodeling of the distal lung septae and arteries. Mutant lung histology at the saccular phase shows mesenchymal and saccular wall thickening, and abnormal proliferation of α-smooth muscle actin-positive cells, as well as increased mesenchymal/fibroblast cell differentiation, which become more sever when deleting both genes. Our study indicates that SHH but not TGF-ß signaling pathway is a central mediator for the histologic alterations described in the saccular phenotype of Eya1(-/-) or Six1(-/-) lungs. Indeed, genetic reduction of SHH activity in vivo or inhibition of its activity in vitro substantially rescues lung mesenchymal and alveolar phenotype of mutant mice at the saccular phase. These findings uncover novel functions for Six1-Eya1-SHH pathway during the saccular phase of lung morphogenesis, providing a conceptual framework for future mechanistic and translational studies in this area.

Eya1 protein phosphatase regulates tight junction formation in lung distal epithelium.

Little is known about the regulatory mechanisms underlying lung epithelial tight junction (TJ) assembly, which is inextricably linked to the preservation of epithelial polarity, and is highly coordinated by proteins that regulate epithelial cell polarity, such as aPKCζ. We recently reported that Eya1 phosphatase functions through aPKCζ-Notch1 signaling to control cell polarity in the lung epithelium. Here, we have extended these observations to TJ formation to demonstrate that Eya1 is crucial for the maintenance of TJ protein assembly in the lung epithelium, probably by controlling aPKCζ phosphorylation levels, aPKCζ-mediated TJ protein phosphorylation and Notch1-Cdc42 activity. Thus, TJs are disassembled after interfering with Eya1 function in vivo or during calcium-induced TJ assembly in vitro. These effects are reversed by reintroduction of wild-type Eya1 or partially inhibiting aPKCζ in Eya1siRNA cells. Moreover, genetic activation of Notch1 rescues Eya1(-/-) lung epithelial TJ defects. These findings uncover novel functions for the Eya1-aPKCζ-Notch1-Cdc42 pathway as a crucial regulatory mechanism of TJ assembly and polarity of the lung epithelium, providing a conceptual framework for future mechanistic and translational studies in this area.

Evaluation of the effect of hydroalcoholic extract of Zingiber officinale rhizomes in rat collagen-induced arthritis.

Patients with chronic, painful diseases often seek alternative therapy. The purpose of this study was to investigate the potential of hydroalcoholic extract of Zingiber officinale rhizomes (Z. officinale extract) to ameliorate inflammatory process in rat collagen-induced arthritis. Our results show that Z. officinale extract in doses higher than 50 mg/kg/day intraperitoneally starting from the dose of booster immunization and for 26 days can ameliorate the clinical scores, disease incidence, joint temperature and swelling, and cartilage destruction, together with reduction of serum levels of interleukin (IL)-1beta, IL-2, IL-6, tumour necrosis factor-alpha, and anti-CII antibodies. Moreover, Z. officinale extract at the dose of 200 mg/kg/day was superior to 2 mg/kg/day of indomethacin at most of the measured parameters. These observations might make Z. officinale extract a good alternative to non-steroidal anti-inflammatory drugs for patients with rheumatoid arthritis.

Hyper-adhesion in desmosomes: its regulation in wound healing and possible relationship to cadherin crystal structure.

The resistance of tissues to physical stress is dependent upon strong cell-cell adhesion in which desmosomes play a crucial role. We propose that desmosomes fulfil this function by adopting a more strongly adhesive state, hyper-adhesion, than other junctions. We show that the hyper-adhesive desmosomes in epidermis resist disruption by ethylene glycol bis(2-aminoethyl ether)-N,N,N'N'-tetraacetic acid (EGTA) and are thus independent of Ca2+. We propose that Ca2+ independence is the normal condition for tissue desmosomes. Ca2+ independence is associated with an organised arrangement of the intercellular adhesive material exemplified by a dense midline. When epidermis is wounded, desmosomes in the wound-edge epithelium lose hyper-adhesiveness and become Ca2+ dependent, i.e. readily dissociated by EGTA. Ca2+-dependent desmosomes lack a midline and show narrowing of the intercellular space. We suggest that this indicates a less-organised, weakly adhesive arrangement of the desmosomal cadherins, resembling classical cadherins in adherens junctions. Transition to Ca2+ dependence on wounding is accompanied by relocalisation of protein kinase C alpha to desmosomal plaques suggesting that an 'inside-out' transmembrane signal is responsible for changing desmosomal adhesiveness. We model hyper-adhesive desmosomes using the crystal packing observed for the ectodomain of C-cadherin and show how the regularity of this 3D array provides a possible explanation for Ca2+ independence.

Suprabasal desmoglein 3 expression in the epidermis of transgenic mice results in hyperproliferation and abnormal differentiation.

The desmoglein 1 (Dsg1) and desmocollin 1 (Dsc1) isoforms of the desmosomal cadherins are expressed in the suprabasal layers of epidermis, whereas Dsg3 and Dsc3 are more strongly expressed basally. This differential expression may have a function in epidermal morphogenesis and/or may regulate the proliferation and differentiation of keratinocytes. To test this hypothesis, we changed the expression pattern by overexpressing human Dsg3 under the control of the keratin 1 (K1) promoter in the suprabasal epidermis of transgenic mice. From around 12 weeks of age, the mice exhibited flaking of the skin accompanied by epidermal pustules and thinning of the hair. Histological analysis of affected areas revealed acanthosis, hypergranulosis, hyperkeratosis, localized parakeratosis, and abnormal hair follicles. This phenotype has some features in common with human ichthyosiform diseases. Electron microscopy revealed a mild epidermal spongiosis. Suprabasally, desmosomes showed incorporation of the exogenous protein by immunogold labeling but were normal in structure. The epidermis was hyperproliferative, and differentiation was abnormal, demonstrated by expression of K14 in the suprabasal layer, restriction of K1, and strong induction of K6 and K16. The changes resembled those found in previous studies in which growth factors, cytokines, and integrins had been overexpressed in epidermis. Thus our data strongly support the view that Dsg3 contributes to the regulation of epidermal differentiation. Our results contrast markedly with those recently obtained by expressing Dsg3 in epidermis under the involucrin promoter. Possible reasons for this difference are considered in this paper.