Abnormal Morphological Changes Research Articles

The effects of exposure to and timing of a choline-deficient diet during pregnancy and early postnatal life on the skeletal muscle transcriptome of the offspring

Nonalcoholic fatty liver disease (NAFLD) is related to muscle loss, but the precise mechanism underlying this association remains unclear. The aim of the present study was thus to determine the influence of maternal fatty liver and dietary choline deficiency during pregnancy and/or lactation periods on the skeletal muscle gene expression profile among 24-day-old male rat offspring. Histological examination of skeletal muscle tissue specimens obtained from offspring of dams suffering from fatty liver, provided with proper choline intake during pregnancy and lactation (NN), fed a choline-deficient diet during both periods (DD), deprived of choline only during pregnancy (DN), or only during lactation (ND), was performed. The global transcriptome pattern was assessed using a microarray approach (Affymetrix® Rat Gene 2.1 ST Array Strip). The relative expression of selected genes was validated by real-time PCR (qPCR). Morphological differences in fat accumulation in skeletal muscle related to choline supply were observed. The global gene expression profile was consistent with abnormal morphological changes. Mettl21c gene was overexpressed in all choline-deficient groups compared to the NN group, while two genes, Cdkn1a and S100a4, were downregulated. Processes of protein biosynthesis were upregulated, and processes related to cell proliferation and lipid metabolism were inhibited in DD, DN, and ND groups compared to the NN group. Prenatal and early postnatal exposure to fatty liver and dietary choline deficiency leads to changes in the transcriptome profile in skeletal muscle of 24-day old male rat offspring and is associated with muscle damage, but the mechanism of it seems to be different at different developmental stages of life. Adequate choline intake during pregnancy and lactation can prevent severe muscle disturbance in the progeny of females suffering from fatty liver.

An Acid-Responsive Iron-Based Nanocomposite for OSCC Treatment

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, characterized by invasiveness, local lymph node metastasis, and poor prognosis. Traditional treatment and medications have limitations, making the specific inhibition of OSCC growth, invasion, and metastasis a challenge. The tumor microenvironment exhibits mildly acidity and high concentrations of H2O2, and its exploitation for cancer treatment has been widely researched across various cancers, but research in the oral cancer field is relatively limited. In this study, by loading ultra-small Prussian blue nanoparticles (USPBNPs) into mesoporous calcium–silicate nanoparticles (MCSNs), we developed an acid-responsive iron-based nanocomposite, USPBNPs@MCSNs (UPM), for the OSCC treatment. UPM demonstrated excellent dual enzyme activities, generating toxic ·OH in a mildly acidic environment, effectively killing OSCC cells and producing O2 in a neutral environment to alleviate tissue hypoxia. The results showed that UPM could effectively inhibit the proliferation, migration, and invasion of OSCC cells, as well as the growth of mice solid tumors, without obvious systemic toxicity. The mechanisms may involve UPM inducing ferroptosis of OSCC cells by downregulating the xCT/GPX4/glutathione (GSH) axis, characterized by intracellular iron accumulation, reactive oxygen species accumulation, GSH depletion, lipid peroxidation, and abnormal changes in mitochondrial morphology. Therefore, this study provides empirical support for ferroptosis as an emerging therapeutic target for OSCC and offers a valuable insight for future OSCC treatment.

Forkhead-associated phosphopeptide binding domain 1 (FHAD1) deficiency impaired murine sperm motility.

Genetic knockout-based studies conducted in mice provide a powerful means of assessing the significance of a gene for fertility. Forkhead-associated phosphopeptide binding domain 1 (FHAD1) contains a conserved FHA domain, that is present in many proteins with phospho-threonine reader activity. How FHAD1 functions in male fertility, however, remains uncertain. Fhad1-/- mice were generated by CRISPR/Cas9-mediated knockout, after which qPCR was used to evaluate changes in gene expression, with subsequent analyses of spermatogenesis and fertility. The testis phenotypes were also examined using immunofluorescence and histological staining, while sperm concentrations and motility were quantified via computer-aided sperm analysis. Cellular apoptosis was assessed using a TUNEL staining assay. The Fhad1-/-mice did not exhibit any abnormal changes in fertility or testicular morphology compared to wild-type littermates. Histological analyses confirmed that the testicular morphology of both Fhad1-/-and Fhad1+/+ mice was normal, with both exhibiting intact seminiferous tubules. Relative to Fhad1+/+ mice, however, Fhad1-/-did exhibit reductions in the total and progressive motility of epididymal sperm. Analyses of meiotic division in Fhad1-/-mice also revealed higher levels of apoptotic death during the first wave of spermatogenesis. The findings suggest that FHAD1 is involved in both meiosis and the modulation of sperm motility.

Fetal growth restriction exhibits various mTOR signaling in different regions of mouse placentas with altered lipid metabolism

Fetal growth restriction (FGR) is a common complication of pregnancy and can have significant impact on obstetric and neonatal outcomes. Increasing evidence has shown that the inhibited mechanistic target of rapamycin (mTOR) signaling in placenta is associated with FGR. However, interpretation of existing research is limited due to inconsistent methodologies and varying understanding of the mechanism by which mTOR activity contributes to FGR. Hereby, we have demonstrated that different anatomic regions of human and mouse placentas exhibited different levels of mTOR activity in normal compared to FGR pregnancies. When using the rapamycin-induced FGR mouse model, we found that placentas of FGR pregnancies exhibited abnormal morphological changes and reduced mTOR activity in the decidual-junctional layer. Using transcriptomics and lipidomics, we revealed that lipid and energy metabolism was significantly disrupted in the placentas of FGR mice. Finally, we demonstrated that maternal physical exercise during gestation in our FGR mouse model was associated with increased fetal and placental weight as well as increased placental mTOR activity and lipid metabolism. Collectively, our data indicate that the inhibited placental mTOR signaling contributes to FGR with altered lipid metabolism in mouse placentas, and maternal exercise could be an effective method to reduce the occurrence of FGR or alleviate the adverse outcomes associated with FGR.Graphical Human and mouse placentas have different mTOR signaling activities in different anatomic regions in normal and FGR pregnancies.Pregnant mice with FGR induced by rapamycin show smaller placentas, decreased mTOR activity in DJ layer of placenta and altered lipid metabolism.Maternal exercise partially alleviates the abnormal outcomes of FGR model.

Hair Follicle Damage after 100 mGy Low-Dose Fractionated X-Ray Irradiation and the Protective Effects of TEMPOL, a Stable Nitroxide Radical, against Radiation.

The effects of long-term low-dose X-ray irradiation on the outer root sheath (ORS) cells of C3H/He mice were investigated. Mice were irradiated with a regime of 100 mGy/day, 5 days/week, for 12 weeks (Group X) and the results obtained were compared to those in a non-irradiated control (Group C). Potential protection against ORS cells damage induced by this exposure was investigated by adding the stable nitroxide radical 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) at 1 mM to the drinking water of mice (Group X + TEMPOL). The results obtained were compared with Group C and a non-irradiated group treated with TEMPOL (Group C + TEMPOL). After fractionated X-ray irradiation, skin was removed and ORS cells were examined by hematoxylin and eosin staining and electron microscopy for an abnormal nuclear morphology and nuclear condensation changes. Fractionated X-irradiated mice had an increased number of ORS cells with an abnormal nuclear morphology as well as nuclear condensation changes. Sections were also immunohistochemically examined for the presence of TdT-mediated dUTP nick-end labeling (TUNEL), 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), vascular endothelial growth factor (VEGF), nitrotyrosine, heme oxygenase 1 (HO-1), and protein gene product 9.5 (PGP 9.5). Significant increases were observed in TUNEL, 8-OHdG, and 4-HNE levels in ORS cells from mice in Group X. Electron microscopy also showed irregular shrunken ORS cells in Group X. These changes were prevented by the presence of TEMPOL in the drinking water of the irradiated mice. TEMPOL alone had no significant effects. These results suggest that fractionated doses of radiation induced oxidative damage in ORS cells; however, TEMPOL provided protection against this damage, possibly as a result of the rapid reaction of this nitroxide radical with the reactive oxidants generated by fractionated X-ray irradiation.

The association between oral inflammatory load and semen and sperm functional analysis: A cross-sectional study.

Studies have suggested a correlation between periodontitis and reduced male fertility. Inflammation has been described as the link between these ailments. Oral inflammatory load (OIL) can be measured through oral polymorphonuclear neutrophil (oPMN) count, which is associated with periodontal diseases. This cross-sectional study assessed the possible correlation between OIL and the functional parameters of sperm cells. In 229 volunteers, oral rinse and semen samples were assessed for oPMN, semen polymorphonuclears (sPMNs), sperm concentration, total sperm count, motility, morphology, and sperm DNA fragmentation index (SDFi). A multiple linear regression model was conducted to evaluate the relationships between oPMN and semen parameters. The effect of elevated oPMN counts on total motility rate, progressive rate, and percentage of sperm cells with normal morphology was significant (P<0.001), with an inverse relationship, i.e., with every unit increase in oPMN count, the mentioned parameters would decline by 0.573, 0.367, and 0.407 units, respectively. oPMN counts also correlated positively with sPMN counts and SDFi (P<0.001), i.e., with every unit increase in the oPMN measures, sPMN counts would increase by 0.126 million/mL, with an 0.733% increase in SDFi. However, there was no significant association between oPMN counts and sperm concentration. OIL, as represented by oPMN counts, might affect male fertility as there is a positive correlation between the levels of these inflammatory cells and decreased sperm motility, abnormal morphological changes, increased sPMN counts, and increased SDFi.

Effects of aerobic exercise on depression-like behavior and TLR4/NLRP3 pathway in hippocampus CA1 region of CUMS-depressed mice

Background and purposeThe paper observes regulation of the expression levels of NLRP3 and TLR4 in hippocampal CA1 neurons in CUMS mice by aerobic exercise with constructing CUMS depression mouse model, in order to explore the neuroprotective mechanism of aerobic exercise on the hippocampus of depressed mice. Study design and method24 healthy male 8-week-old C57BL/6 mice were randomly divided into CG, MG and ME. Thirteen stress-stimulating factors were randomly formulated into a CUMS stress-stimulating program. The mice were underwent 28 days of CUMS depression model, referenced clinical means for experimental research. The study was approved by the Ethics Committee of Yichun University (YCUEC IRB number LSK NO.2022.18). After model preparation, ME mice were subjected to moderate-intensity treadmill exercise training for 8 weeks. TST, FST and SPT were used to detect the depression-like behaviors of the mice in each group. Nissl staining was used to compare the cell morphology in the CA1 region of the mouse hippocampus. Immunohistochemical staining and western blot were used to detect the changes in the expression levels of NLRP3, TLR4 and other proteins in the CA1 region of the mouse hippocampus. ResultsThe results of neurobehavioral assessment showed that, the immobility time of TST and FST were significantly increased, and SPT index was significantly decreased of MG mice. Compared with MG, ME mice significantly improved depression-like behaviors such as TST, FST and SPT index. Nissl staining showed that the morphology of neurons in CA1 region of hippocampus of MG mice were mostly vacuolar-like, with severe nuclear pyknosis. Abnormal morphological changes such as vacuolar-like and pyknotic pyknosis of neurons in the hippocampal CA1 region of ME mice were significantly reduced. Protein expression test showed that the number of NLRP3, TLR4, IL-1β and IL-10 positive neurons in hippocampal CA1 region of MG mice increased significantly compared with CG, and the proportion of positive cells increased significantly, while NLRP3 and TLR4 positive neurons in the hippocampal CA1 region of ME mice were significantly reduced, the proportion of TLR4 positive cells was significantly reduced. ConclusionSystematic moderate-intensity exercise can effectively improve the depression-like behavior of CUMS depressed mice through the expression of TLR4/NLRP3 inflammatory signaling pathway, and provide an effective experimental basis for the clinical rehabilitation treatment of depression.

Transient impacts of UV-B irradiation on whole body regeneration in a colonial urochordate

Within the chordates, only some colonial ascidians experience whole body regeneration (WBR), where amputated small colonial fragments containing blood-vessels have the capability to regenerate the entire functional adult zooid within 1–3 weeks. Studying WBR in small colonial fragments taken at different blastogenic stages (the weekly developmental process characteristic to botryllid ascidians) from the ascidian Botrylloides leachii, about half of the fragments were able to complete regeneration (cWBR) three weeks following separation, about half were still in uncomplete, running regeneration (rWBR), and only a small percentage died. cWBR significantly increased in fragments that originated from a late blastogenic stage compared to an early stage. Most B. leachii populations reside in shallow waters, under variable daily natural UV irradiation, and it is of interest to elucidate irradiation effects on development and regeneration. Here, we show that UV-B irradiation resulted in enhanced mortality, with abnormal morphological changes in surviving fragments, yet with non-significant cWBR vs. rWBRs. Further, UV-B irradiation influenced the proportion of blood cells (morula cells, hemoblasts) and of multinucleated cells, a new WBR-associated cell type. At 24-h post-amputation we observed enhanced expression of β-catenin (a signaling pathway that plays indispensable roles in cell renewal and regeneration), H3 and PCNA in all cell types of non-irradiated as compared to irradiated fragments. These elevated levels were considerably reduced 9-days later. Since WBR is a highly complex phenomenon, the employment of specific experimental conditions, as UV-B irradiation, alongside blastogenesis (the weekly developmental process), elucidates undisclosed facets of this unique biological occurrence such as transient expression of signature genes.

Establishment of a facial nerve trunk crush injury model and evaluation of facial nerve self-healing in rats.

To facilitate further investigation into the mechanisms of facial nerve regeneration, a simple and reliable model of facial nerve crush injury is essential. Nevertheless, the establishment of such models lacks standardization and repeatability, while the healing capacity of the nerve is often overlooked, potentially affecting future studies. We made facial nerve trunk crush injury models with different pressing times and detected the changes from the distal nerves to the motoneurons via behavior analysis, electrophysiological test, and histomorphometry analysis. It revealed a particular capacity for self-healing following facial nerve crush damage because there was almost no facial motoneuron apoptosis in the MC group during the observation period, and rats in MC group had total facial paralysis in behavioral tests following surgery and varying degrees of recovery 28 days postoperatively with no treatments. As the pressing time increased, the latency, wave amplitude, nerve fiber damage degree, nerve axon ratio, myelin thickness, electroneurograph (ENoG) value, ultrastructural damage, abnormal morphological changes, and the buccal muscle atrophy of each MC group gradually increased or got worse during the observation period. However, after 28 postoperative days, only the ENoG values of the M10min and M12min groups were beyond 90%, indicating no self-healing. It suggests that a stable model of peripheral facial palsy may be created by applying a 12.5cm mosquito clamped to the facial nerve trunk for at least 10 min, which laid the foundation for the subsequent research to objectively evaluate facial nerve regeneration.

Nailfold Video-Capillaroscopic Changes in Adult Bangladeshi Patients With Systemic Lupus Erythematosus: Correlation With Disease Activity

Background: Peripheral microangiopathy is an important feature in systemic lupus erythematosus (SLE). Nailfold capillary (NFC) changes observed by nailfold videocapillaroscopy (NVC) may play a role in early detection of microangiopathy and assessment of disease activity in SLE. The aim of the study was to evaluate nailfold capillary changes, their diagnostic accuracy and NFC-pattern of changes in a group of Bangladeshi SLE patients in comparison to healthy subjects and to determine the correlation with disease activity in SLE. Methods: This cross-sectional study with a comparison group was conducted in CMCH, Chattogram; a Tertiary Care Hospital in Bangladesh. Results: Twenty-seven (n=27) Bangladeshi SLE patients who were diagnosed by ACR-1997 revised criteria for diagnosis of SLE and Twenty-seven (n=27) age-sex matched health subjects were included. All participants were subjected to full history taking, clinical examination, laboratory investigations as well as NVC examination. SLE disease activity was assessed by SLEDIA scoring tool and nailfold capillary changes were assessed with NFC-pattern of changes by applying NVC. Results: Mean (±SD) age of the SLE patient group was 31.2 (±7.8) years and female to male ratio was around 6:1. 23 out of 27(85.2%) patients had multiple phenotypes and 18 (66.6%) had either high or very high disease activity. Sub-papillary venous plexus (SPVP) was prominently visible more frequently in SLE patients and capillary density was reduced in SLE patients compared with healthy controls. Capillary changes in NVC were observed in 26 out of 27 (96.3%) patients. Major and scleroderma pattern were detected in 51.9% and 11.1% of the SLE patients; respectively. Nailfold capillary abnormalities were significantly more frequent in SLE patient than in healthy controls. More frequently found different abnormal morphological changes were seen with crossed capillary (66.7%), tortuous capillary (63%) and meandering capillary (37%). There was a significant positive correlation between disease activity of SLE and NFC-pattern of changes (r=0.443, p=0.021). Conclusion: Different abnormal nailfold capillary changes are quite common among patients with SLE, and nailfold capillary changes positively correlate with disease activity in SLE. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 208

Analysis of corneal topographic and endothelial cell properties in newly diagnosed obstructive sleep apnea patients: A case-control study

PurposeTo investigate the topographic features and endothelial cell changes in the corneas of patients with newly diagnosed obstructive sleep apnea (OSA). BackgroundThis cross-sectional case-control study included 98 patients with OSA and 90 healthy controls. OSA was diagnosed on the basis of a polysomnographic sleep examination. Patients with OSA were grouped according to their apnea-hypopnea index (AHI) scores. Corneal topographic measurements were obtained using the Scheimpflug–Placido disk topographer, and keratometry values, anterior chamber parameters, thinnest corneal thickness, symmetry index (SI), keratoconus vertex (KV), and the Baiocchi-Calossi-Versaci index, including keratoconus (KC) screening indexes, were recorded. The corneal endothelium was visualizedby specular microscopy, and the endothelial cell density, coefficient of variability (CV), and percentage of hexagonal cells (HEX) were recorded. ResultsIn this study, 32 patients had mild, 34 patients had moderate, and 32 patients had severe OSA. The mean back KV (KVb) and back SI values were significantly higher in the OSA group than in the control group (P <0.001, P = 0.035, respectively). As body mass index (BMI) increased, KVb also increased significantly (r = 0.281; P = 0.009). The mean CV and HEX values differed significantly between the OSA and control groups (P = 0.012 and P = 0.002, respectively). In addition, a significant correlation was found between AHI and KVb and CV values (r = 0.315; P <0.001 and r = 0.231; P = 0.011, respectively). ConclusionsThis study revealed abnormal changes in the corneal endothelial morphology and topographic KC screening indexes in relation to OSA severity in patients and controls. Further research is required to determine the effect of BMI on corneal topographic findings in patients with OSA.

A strategy to treat coagulopathy in patients with massive hemorrhage

To investigate the topographic features and endothelial cell changes in the corneas of patients with newly diagnosed obstructive sleep apnea (OSA).This cross-sectional case-control study included 98 patients with OSA and 90 healthy controls. OSA was diagnosed on the basis of a polysomnographic sleep examination. Patients with OSA were grouped according to their apnea-hypopnea index (AHI) scores. Corneal topographic measurements were obtained using the Scheimpflug–Placido disk topographer, and keratometry values, anterior chamber parameters, thinnest corneal thickness, symmetry index (SI), keratoconus vertex (KV), and the Baiocchi-Calossi-Versaci index, including keratoconus (KC) screening indexes, were recorded. The corneal endothelium was visualizedby specular microscopy, and the endothelial cell density, coefficient of variability (CV), and percentage of hexagonal cells (HEX) were recorded.In this study, 32 patients had mild, 34 patients had moderate, and 32 patients had severe OSA. The mean back KV (KVb) and back SI values were significantly higher in the OSA group than in the control group (P <0.001, P = 0.035, respectively). As body mass index (BMI) increased, KVb also increased significantly (r = 0.281; P = 0.009). The mean CV and HEX values differed significantly between the OSA and control groups (P = 0.012 and P = 0.002, respectively). In addition, a significant correlation was found between AHI and KVb and CV values (r = 0.315; P <0.001 and r = 0.231; P = 0.011, respectively).This study revealed abnormal changes in the corneal endothelial morphology and topographic KC screening indexes in relation to OSA severity in patients and controls. Further research is required to determine the effect of BMI on corneal topographic findings in patients with OSA.

Sterols, free fatty acids, and total fatty acid content in the massive Porites spp. corals cultured under different pCO2 and temperature treatments

Lipids may serve as energy reserves to support coral calcification, allow acclimation to higher temperatures, and are implicated in the control of CaCO3 precipitation. Here, we report the lipid composition of the soft tissues (including host and symbionts) of 7 massive Porites spp. coral colonies (4 × P. lutea and 3 × P. murrayensis), which were cultured under different pCO2 concentrations (180, 260, 400 and 750 µatm) and at two temperatures (25 ℃ and 28 ℃), below the thermal stress threshold. We report the fatty acid methyl esters (FAME), free fatty acid (FFA) to total fatty acid content, sterol and wax ester profiles, and identify two ketones (n-alkanone) and three long chain aldehyde (n-alkanal) derivatives. Increasing seawater temperature significantly increases the contributions of FFAs to the total lipids, of C18:2 and C20:0 to the total FFA pool, of C14:0 to total FAME, and of campesterol to total sterol. The temperature increase also reduces the contributions of unusual fatty acid derivatives to total lipids, of C14:0, C15:0, C16:0 and C17:0 saturated free fatty acids to total FFAs, and of C16:0 FA to total FAME. Fatty acids are implicated in the control of membrane structure fluidity and the observed changes may promote acclimation and thermostability as temperature varies. Seawater pCO2 has no significant effect on the composition of tissue lipids with the exception that the contribution of C14:0 FA to total lipid content is significantly lower at 180 µatm compared to 260 and 750 µatm. Decreased contribution of total sterols and unusual fatty acid derivatives and increased contribution of total FFAs to total lipids are observed in the fastest calcifying coral (a P. lutea specimen) compared to the other corals, under all pCO2 and temperature conditions. Although a rapid calcifier this genotype has been shown previously to exhibit pronounced abnormal changes in skeletal morphology in response to decreased seawater pCO2. Variations in tissue lipid composition between coral genotypes may influence their resilience to future climate change.

Ameliorative effect of lycopene alone and in combination with co-enzyme Q10 in streptozotocin-induced diabetic nephropathy in experimental rats

Diabetic nephropathy (DN) has become an utmost reason for long-standing renal dysfunction and end-stage renal disease globally. Oxidative stress induced by persistent hyperglycemia is considered a fundamental element in the evolution of DN. The goal of this research was to discover the outcome of appendages of natural antioxidants such as lycopene and co-enzyme Q10 (CoQ10) in DN rats and to observe the preventive effects in DN. A diabetes model was developed in a Wistar strain of male rats (200–250 g) by subcutaneous injection of streptozotocin (55 mg/kg). Development of nephropathy was assessed by renal function tests including blood glucose, creatinine, albumin, total protein, total bilirubin, uric acid, total cholesterol, triglycerides, and CRP level. Oxidative stress markers such as LPO and GSH content and activity of membrane-bound Na+/K+ ATPases were measured in kidney homogenate. Renal damage was assessed by performing a histopathological analysis. DN rats showed a significant elevation in creatinine, albumin, total protein, total bilirubin, uric acid, total cholesterol, triglycerides, CRP, and LPO levels whereas a significant reduction in creatinine clearance and GSH level. Treatment with antioxidants such as lycopene (5 mg/kg/p.o.) and CoQ10 (10 mg/kg/p.o.) along with their combination for 4 weeks notably altered the level of renal function biomarkers and oxidative stress markers. These antioxidants and their combination also protected the kidney from abnormal morphological changes. The present findings suggest that the combined administration of lycopene and CoQ10, which are antioxidants, exhibits synergistic effects in mitigating renal injury by reducing hyperglycemia, oxidative stress markers, and histopathological alterations.

Honeycomb-like Structured Film, a Novel Therapeutic Device, Suppresses Tumor Growth in an In Vivo Ovarian Cancer Model.

Ovarian cancer cell dissemination can lead to the mortality of patients with advanced ovarian cancer. Complete surgery for no gross residual disease contributes to a more favorable prognosis than that of patients with residual disease. HCFs have highly regular porous structures and their 3D porous structures act as scaffolds for cell adhesion. HCFs are fabricated from biodegradable polymers and have been widely used in tissue engineering. This study aimed to show that HCFs suppress tumor growth in an in vivo ovarian cancer model. The HCF pore sizes had a significant influence on tumor growth inhibition, and HCFs induced morphological changes that rounded out ovarian cancer cells. Furthermore, we identified gene ontology (GO) terms and clusters of genes downregulated by HCFs. qPCR analysis demonstrated that a honeycomb structure downregulated the expression of CXCL2, FOXC1, MMP14, and SNAI2, which are involved in cell proliferation, migration, invasion, angiogenesis, focal adhesion, extracellular matrix (ECM), and epithelial-mesenchymal transition (EMT). Collectively, HCFs induced abnormal focal adhesion and cell morphological changes, subsequently inhibiting the differentiation, proliferation and motility of ovarian cancer cells. Our data suggest that HCFs could be a novel device for inhibiting residual tumor growth after surgery, and could reduce surgical invasiveness and improve the prognosis for patients with advanced ovarian cancer.

A de novo gene originating from the mitochondria controls floral transition in Arabidopsis thaliana.

De novo genes created in the plant mitochondrial genome have frequently been transferred into the nuclear genome via intergenomic gene transfer events. Therefore, plant mitochondria might be a source of de novo genes in the nuclear genome. However, the functions of de novo genes originating from mitochondria and the evolutionary fate remain unclear. Here, we revealed that an Arabidopsis thaliana specific small coding gene derived from the mitochondrial genome regulates floral transition. We previously identified 49 candidate de novo genes that induce abnormal morphological changes on overexpression. We focused on a candidate gene derived from the mitochondrial genome (sORF2146) that encodes 66 amino acids. Comparative genomic analyses indicated that the mitochondrial sORF2146 emerged in the Brassica lineage as a de novo gene. The nuclear sORF2146 emerged following an intergenomic gene transfer event in the A. thaliana after the divergence between Arabidopsis and Capsella. Although the nuclear and mitochondrial sORF2146 sequences are the same in A. thaliana, only the nuclear sORF2146 is transcribed. The nuclear sORF2146 product is localized in mitochondria, which may be associated with the pseudogenization of the mitochondrial sORF2146. To functionally characterize the nuclear sORF2146, we performed a transcriptomic analysis of transgenic plants overexpressing the nuclear sORF2146. Flowering transition-related genes were highly regulated in the transgenic plants. Subsequent phenotypic analyses demonstrated that the overexpression and knockdown of sORF2146 in transgenic plants resulted in delayed and early flowering, respectively. These findings suggest that a lineage-specific de novo gene derived from mitochondria has an important regulatory effect on floral transition.

Effects of Whey Peptide Supplementation on Sarcopenic Obesity in High-Fat Diet-Fed Mice.

The incidence of sarcopenic obesity gradually increased in parallel with the aged population. This research examined the effects of whey peptide (WP) supplementation with/without resistant exercise (RE) on sarcopenic obesity. Male 8-month-old C57BL/6J mice were fed a control diet (10 kcal% fat) or a high-fat diet (60 kcal% fat) for 8 weeks. High-fat diet-fed mice were randomly divided into four groups: obesity control group (OB), RE (RE only), WP (WP only), and WPE (RE and WP). WP supplementation (1500 mg/day/kg B.W.) gavage and RE (ladder climbing, five times weekly, 8–10 repetitions, 10–20% B.W. load) were conducted for an additional 8 weeks. Protein and mRNA levels of markers related to energy, protein, and lipid metabolism were analyzed in skeletal muscle and adipose tissue by one-way analysis of variance (ANOVA). WP supplementation regardless of RE significantly suppressed the increasing fat mass (p = 0.016) and decreasing lean mass (p = 0.014) and alleviated abnormal morphological changes in skeletal muscle and adipose tissue (p < 0.001). In adipose tissue, WP supplementation regardless of RE ameliorated dysregulated energy metabolism and contributed to the reduction in adipocyte differentiation (PPAR-γ (p = 0.017), C/EBPα (p = 0.034)). In skeletal muscle, WP supplementation regardless of RE alleviated energy metabolism dysregulation and resulted in down-regulated protein degradation (Atrogin-1 (p = 0.003), MuRF1 (p = 0.006)) and apoptosis (Bax) (p = 0.004). Taken together, the current study elucidated that WP supplementation regardless of RE has potential anti-obesity and anti-sarcopenic effects in sarcopenic obesity.

Andrographolide restored production performances and serum biochemical indexes and attenuated organs damage in Mycoplasma gallisepticum-infected broilers

ABSTRACT 1. This study aimed to study the preventive and therapeutic effects of andrographolide (Andro) during Mycoplasma gallisepticum HS strain (MG) infection in ArborAcres (AA) broilers. 2. The minimum inhibitory concentration (MIC) of Andro against MG was measured. Broiler body weight, feed efficiency, morbidity, cure rate and mortality were recorded during the experiment. Air sac lesion scores and immune organ index were calculated. Expression of pMGA1.2 in lung tissue and serum biochemical indices were examined. Histopathological examinations of immune organs, liver, trachea and lung tissue were conducted by Haematoxylin and Eosin stain. 3. MIC was 3.75 μg/mL and Andro significantly inhibited the expression of pMGA1.2 (P ≤ 0.05). Compared with control MG-infected group, Andro low-dose and high-dose prevention reduced the morbidity of chronic respiratory disease in 40.00% and 50.00%, respectively. Mortality of C, D and E group was 16.67%, 10.00% and 6.67%, respectively. Cure rate of E, F, G and H group was 92.00%, 92.86%, 93.33% and 100.0%, respectively. Compared with control MG-infected group, Andro treatment significantly increased average weight gain (AWG), relative weight gain rate (RWG) and feed conversion rate (FCR) at 18 to 24 days (P ≤ 0.05). Compared with control group, Andro alone treatment significantly increased AWG in broilers (P ≤ 0.05). 4. Compared with control MG-infected group, Andro significantly attenuated MG-induced air sac lesion, immune organs, liver, trachea and lung damage in broilers. Andro alone treatment did not induce abnormal morphological changes in these organs in healthy broilers. Serum biochemical analysis results showed, comparing with control MG-infected group, Andro significantly decreased the content of total protein, albumin, globulin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, urea, creatinine, uric acid, total cholesterol, and increased the albumin/globulin ratio and content of alkaline phosphatase, apolipoprotein B and apolipoprotein A-I in a dose-dependent manner (P ≤ 0.05). 5. Andro could act as a potential agent against MG infection in broilers.

Potential Effects of Resistant Exercise on Cognitive and Muscle Functions Mediated by Myokines in Sarcopenic Obese Mice.

Recently, it has been demonstrated that in sarcopenic obesity (SO), physical activity could improve cognitive functions. Moreover, previous studies suggested that muscle contraction could influence cognitive function via myokines. This study investigated the potential effects of resistant exercise on cognitive and muscle functions in SO. SO was induced by a high-fat diet treatment for 8 weeks in 8-month-old male C57BL/6J mice. Then, resistant exercise (ladder climbing) for 8 weeks was performed. Muscle and cognitive function tests and morphological analysis were conducted. The protein levels of myokines were investigated in muscle, plasma, and the hippocampus in sarcopenic obese mice. Muscle and cognitive functions were significantly elevated in the obesity-exercise group (EX) compared to the obesity-control group (OB). Interestingly, muscle function was positively correlated with cognitive function. Abnormal morphological changes in the hippocampus were ameliorated in EX compared to OB, but not in the muscle. Protein levels of cognitive function-related myokines and energy metabolism-related markers in EX were significantly elevated in both muscle and hippocampus compared to those in OB. Interestingly, the protein level of brain-derived neurotrophic factor (BDNF) in EX was simultaneously increased in all tissues including muscle, plasma, and hippocampus compared to that in OB. In conclusion, modulation of muscle-derived cognitive function-related myokines in various pathological conditions via a resistant exercise could be a possible way of relieving muscle and cognitive dysfunction.

Protective role of Curcumin in Di-n-butyl phthalate-induced damage on reproductive parameters in male Rabbits

Di-n-butyl phthalate (DBP) is a ubiquitous environmental pollutant, extensively used as a plasticizer in many products including plastics, cosmetics, and medical devices. Some studies have shown that DBP has potential testicular toxicity. The aim of this study was to explore the adverse effects of DBP on testes and epididymis weight, sperm head counts, sperm motility, abnormal changes in sperm morphology, in male rabbits as well as to assess ameliorating role of curcumin. The present study was carried out to evaluate the protective effects of curcumin (from the rhizome, Curcuma longa L.) on the di-n-butylphthalate (DBP)-induced damage in reproductive rabbits. The dose of curcumin (60 mg/kg) and curcumin(60 mg/kg) plus DBP 700 mg/kg were administered per gavage to male rabbits for 30 consecutive days and reproductive parameters were determined.. The results indicated that DBP administration (700 mg/kg) significantly decreased testosterone level, count and motility of sperms, and testis weight compared to control group. However, administration of curcumin with DBP increased reproductive indices in most of the groups compared to DBP-treated groups. DBP-treated rabbits showed marked degeneration of the seminiferous tubules with necrosis and defoliation of spermatocytes .Our research demonstrated that DBP-induced injuries in spermatological parameters and histological structure of testis were recovered by treatment with curcumin Thus, it seems that curcumin inhibits DBP-induced adverse effects on reproductive parameters. The protective effects of these compounds may be due to their intrinsic antioxidant properties and as such may prove useful in combating phthalate-induced reproductive toxicity.