Normal Morphological Structure Research Articles

Neuro-pharmacological Assessment of Coleus forskohlii for Anti-compulsive Activity in Swiss Albino Mice

Background: Obsessive-Compulsive Disorder (OCD) is a common psychiatric illness characterized by obsessions or compulsions that significantly disrupt or impair daily functioning. Coleus forskohlii, a significant medicinal crop, has forskolin in its roots. It is utilized extensively as food and medicine all over the world. Coleus forskohlii has reputed medicinal uses, which include antidepressant, antiaggregant, cAMP-genic, anticancer, etc. Objective: This study used mice models of marble burying and nestlet shredding to assess the potential efficacy of Coleus forskohlii against obsessive-compulsive disorder. 8-hydroxy-2-(di-npropylamino) tetralin (8-OH-DPAT) induced compulsive checking can demonstrate OCD-like repetitive and obsessive behavior as well as neurotransmitter imbalance (serotonin). Methods: Each group had six mice, and the therapy was administered to the animals for a total of 15 days. On days 1, 7, and 14, the marble burying test was assessed for 30 minutes, and on days 2, 8 and 15, the nestlet shredding test was assessed for 30 minutes. The T-maze paradigm was used to assess anti-OCD activity. The brain histology and morphometry were also performed. Results: When compared to the control group, treatments with Coleus forskohlii (50 and 100 mg/kg, p.o.) significantly enhanced performance on both behavior tests. The SAB score is dramatically increased following the administration of the 8-OH-DPAT (2 mg/kg, i.p.) group. Coleus forskohlii (50 and 100 mg/kg, p.o.) and fluoxetine (15 mg/kg, p.o.) groups showed significantly lowered results. Animals treated with 8-OH-DPAT showed a considerable reduction in serotonin levels. Following Coleus forskohlii administration, the histology of the brain tissues showed normal morphological structure with no toxicity or abnormalities. Conclusion: The combination of all these findings points to Coleus forskohlii delivering a possible therapeutic option for the treatment of OCD. The identification and anticompulsive properties of the components from Coleus forskohlii should be the main aim of future studies.

Bovine lactoferrin alleviates aflatoxin B1 induced hepatic and renal injury in broilers by mediating Nrf2 signaling pathway

Aflatoxin B1 (AFB1) a mycotoxin found in chicken feed that possess a global hazard to poultry health. However different potent compounds like bovine lactoferrin (bLF) may prove to be protective effects against AFB1. This study aims to explore the protective effect of bLF against AFB1-induced injury in the liver and kidney in broiler. For this purpose, 600 broilers chicks were randomly alienated into five groups (n=120 each): negative control; positive control (3mg/kg AFB1), and bLF high, medium, and low dosage groups (600 mg/kg, 300 mg/kg, and 150 mg/kg, respectively). The results highlight that AFB1 toxicity in birds exhibited low feed intake, reduction in weight gain, and a decrease in FCR while, bLF regulated these adverse effects. Meanwhile, AFB1 group showed higher levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) and lower levels of superoxide dismutase (SOD) and glutathione (GSHpx) in liver, while urea and creatinine were decline in kidney. Supplementation with bLF effectively controlled these biomarkers and control the negative effects of toxicity. Furthermore, hematoxylin and eosin (H&E) staining exhibited normal morphological structures within liver and kidney in the bLF treated groups, while degenerative changes were observed in AFB1 group. Similarly, bLF, decreased oxidative stress and thus prevented apoptosis in the liver and kidney cells of the birds. Whereas, mRNA level of mitochondrial apoptosis related gene including Bcl-2 (Bak and Bax), caspase-3 and caspase-9 was upregulated, while bcl2 gene were downregulated in AFB1 group. Dietary supplementation of bLF effectively normalizes the expression of these genes. AFB1 exposed birds shown to decrease gene expression level of the crucial component of Nrf2 pathway, responsible to regulate antioxidant defense. Interestingly, bLF reverse these detrimental effects of and restore the normal expression levels of Nrf2 pathway. Conclusively, our findings demonstrate that bLF mitigates the detrimental effects of AFB1, besides regulation of the apoptosis-related genes via mitochondrial pathways. These findings validate that the bLF (600 mg/kg) could be used as protective agent against AFB1-induced liver and kidney damage.

Ulnar bone tuberculosis in children: Case report and literature review.

Tuberculosis of the long tubular bones in children's extremities is infrequent, particularly in the ulna. Early diagnosis poses significant challenges. This report presents a case involving a 2-year-old child with tuberculosis of the ulnar bone, accompanied by a comprehensive review of pertinent literature. The purpose of this study is to share diagnostic and therapeutic experiences and provide potentially valuable insights. In this case, the patient exhibited complete destruction and expansion of the ulnar bone, resulting in a forearm size considerably greater than normal. Concerns were raised about the irreversible deformation of the ulna, the potential for a malignant bone tumor, and its impact on forearm function, potentially endangering the patient's life. The diagnosis was confirmed as tuberculosis of the ulnar bone. The patient underwent surgery to remove the affected ulnar tissue and received anti-tuberculosis medication. Subsequent to treatment, the destruction and expansion of the ulnar bone resolved, with the return of normal ulnar morphology and bone structure. Even in the absence of typical symptoms like fever, weight loss, and loss of appetite, extensive destruction and expansion of a long tubular bone should prompt vigilant consideration of bone tuberculosis.

THE COMPLEX EFFECT OF VITAMIN D AND ALPHA TOCOPHEROL ACETATE ON THE LUNG MICROCIRCULATION IN THE EXPERIMENTAL INDUCTION OF SYSTEMIC SCLEROSIS

Abstract. The aim of the study was to investigate the effects of vitamin D3 (vitamin D) and alpha-tocopherol acetate (vitamin E) on the microcirculatory vessels of the lungs in an experimental model of systemic sclerosis (SSc).
 Methods. We divided the experimental animals into four separate groups: an intact group (IG) consisting of 15 animals, a control group (CG) of 20 animals, experimental group 1 (EG1) and experimental group 2 (EG2) consisting of of 25 animals each. Randomization of groups was carefully performed using the weight variance minimization method. To induce SSc in laboratory animals of EG1, subcutaneous injections of 0.5 ml of 5% sodium hypochlorite (NaClO) were administered 3 times a week for 6 weeks in a row. The CG of rats received an isotonic solution following the same scheme, while the IG was not subjected to any injections. In addition to NaClO, the EG2 received intramuscular injections of vit E (10 mg/100 g) and vit D (1000 IU/100 g) for three weeks during the second half of the experiment.
 After 8 weeks, the animals were euthanized, and lung tissue samples were obtained for histological and electron microscopic analysis. The histological preparations were examined using light microscopy and photographed using a Leica DME light microscope, a DCM 900 digital microscope camera, and a Nicon Coolpix P5100 camera. Meanwhile, the electron microscopy was performed to visualize the ultrastructural characteristics of the lung tissue by use of "PEM-125K" (Selmi, Ukraine) with subsequent photography at magnifications from 2000 to 20000 times.
 All animal procedures were carried out in strict compliance with bioethical principles. The Ethics Commission of the IFNMU granted approval for the study under document number 117/20 on November 19, 2020.
 Results. The histological analysis of the lung specimens of CG animals showed a normal morphological structure. In the EG1, the lungs exhibited abnormalities in the structure of the hemocapillaries, including narrowing of the vessel lumen due to thickening of the vascular wall, edema, and infiltration of polymorphonuclear cells. However, in the EG2, there was an improvement in the histological features, with a reduction in edematous processes and a decrease in the intensity of polymorphonuclear cell infiltration.
 The electron microscopic examination of the lung samples from EG1 animals revealed the presence of platelet adhesion and aggregation, as well as aggregates of erythrocytes within the hemocapillary lumen. Swelling of endothelial cells and narrowing of the hemocapillary lumen were also observed, along with uneven thickening of the basement membrane. In contrast, the combination of vitamins D and E in EG2 animals resulted in improved rheological properties of blood and ultrastructural characteristics of the hemomicrocirculatory elements. The lumen of the hemocapillaries contained single erythrocytes and inactive platelets. The endothelial cells’ membraines showed minimal alterations, with clear contours and no micropinocytotic vesicles or cytoplasmic growths. The nuclei of the endothelial cells had a fine-grained matrix with evenly distributed chromatin granules.
 Conclusions. This study proves that the combined use of vitamins D and E has a positive effect on the state of the microcirculatory vessels in the lungs of experimentally induced systemic sclerosis.

Computed Tomography for Nasal and Paranasal Anatomic Variants

Augmentations and improvements in sinus surgical methods and computed tomography (CT) have concurrently elaborated interest in variable anatomical features of the nasal cavity and paranasal sinuses (PNS). Anatomical variations are normal morphological structures that are present in humans. The presence of these anatomical variations can affect nearby anatomical relations resulting in structural modifications. By the broad perspective of anatomical features in the sinonasal area, certain anatomical characteristics are supposed to be a risk factor for the advancement of sinus pathological conditions and hence it should be essential for the radiologist to be conscious of the variable anatomical structures residing within the nasal and PNS area, significantly if the treatment plan includes surgical procedures. The sinonasal tomographic imaging is required in symptomatic subjects of sinusitis to evaluate the mysterious sinonasal anatomy including morphology, variations, detailed bony visualization, and pathologies within the sinonasal region and surroundings. This review includes studies from 2013-2023 which were extracted from searching databases like Google Scholar, Internet sources, PubMed, Scopus, and Medline to establish a critical review of hidden anatomy of nasal and paranasal sinus region, detected by computed tomography and highlight the operative significance to enhance the surgical outcomes globally.

Konjac glucomannan/low-acyl gellan gum edible coating containing thymol microcapsule regulates cell wall polysaccharides disassembly and delays postharvest softening of blueberries

Softening is one of the crucial factors causing the deterioration of postharvest fruit quality. In this study, the effects of konjac glucomannan/low-acyl gellan gum/microcapsule of thymol (TKL) coating on the storage characteristics, the ultrastructure of cell wall and transcription expression of pectin-related metabolism of blueberries fruits during low-temperature storage were investigated. TKL coating suppressed the expression of pectin-related enzymes disassembly (VaPE2, VaPE3, VaPG3, VaPL2 and Vaβ-Gal2), reduced the activity of cell wall polysaccharide degrading enzymes (PG, PE, PL, β-Gal, α-Man, α-Af, Xth, β-Xyl, Cx, β-Glu), maintained the normal morphological structure and stability of cell wall, and prolonged the shelf life of blueberries fruits. Overall, TKL is a promising coating that can effectively maintain the firmness, inhibit the postharvest softening and prolong the shelf life of the blueberries during storage period.

Carvacrol reduces abnormal and dead sperm counts by attenuating sodium arsenite‐induced oxidative stress, inflammation, apoptosis, and autophagy in the testicular tissues of rats

Arsenic (As) is a highly toxic metalloid. Carvacrol (CAR) is the active ingredient of Lamiaceae plants and has various biological and pharmacological properties. The present study investigated the protective effects of carvacrol (CAR) against testicular toxicity induced by sodium arsenite (SA). Rats were given SA (10mg/kg) and/or CAR (25 or 50 mg/kg) for 14 days. Semen analyzes showed that CAR increased sperm motility and decreased the percentage of abnormal and dead sperm. It was determined that the oxidative stress induced by SA decreased with the increase of Nrf-2 and HO-1 expressions, SOD, CAT, GPx, and GSH levels, and MDA levels decreased after CAR treatment. It was observed that autophagy and inflammation triggered by SA in testicular tissue were alleviated by suppressing the expressions of LC3A, LC3B, MAPK-14, NF-κB, TNF-α, IL-1β, iNOS, and COX-2 biomarkers in rats given CAR. Also, CAR treatment suppressed SA-induced apoptosis by inhibiting Bax and Caspase-3 expressions in testicles and up-regulating Bcl-2 expression. Histopathological analyzes showed that rats given SA had deterioration in tubule structure and spermatogenesis cell line, especially a serious loss of spermatogonia cells, atrophy of seminiferous tubules, and deterioration of germinal epithelium. In the group given CAR, the germinal epithelium and connective tissue were in normal morphological structure and an increase in seminiferous tubule diameters was observed. As a result, it was determined that oxidative stress, inflammation, autophagy, and apoptosis induced by SA were suppressed by CAR, thus protecting the testicular tissue from damage and increasing semen quality.

Phytoecdysteroids and Anabolic Effect of Atriplex dimorphostegia: UPLC-PDA-MS/MS Profiling, In Silico and In Vivo Models.

Atriplex dimorphostegia (Saltbush) is an annual halophytic shrub that is widely distributed across various parts of Asia. The current study is the first to report the metabolites profile of the total ethanol extract of the aerial parts of A. dimorphostegia (TEAD), and its anabolic activity together with the isolated 20-hydroxyecdysone (20-HE) in orchidectomized male rats. TEAD was analyzed and standardized utilizing UPLC-PDA-ESI−MS/MS and UPLC-PDA-UV techniques, resulting in tentative identification of fifty compounds including polyphenols, steroids and triterpenoids. In addition, 20-HE was quantified, representing 26.79 μg/mg of the extract. Phytochemical investigation of TEAD resulted in the isolation of 20-HE from the ethyl acetate fraction (EFAD) and was identified by conventional spectroscopic methods of analysis. Furthermore, the anabolic effect of the isolated 20-HE and TEAD was then evaluated using in silico and in vivo models. Molecular docking experiments revealed in vitro selectivity of 20-HE towards estrogen receptors (ERs), specifically ERβ over ERα and androgenic receptor (AR). The anabolic efficacy of TEAD and 20-HE was studied in orchidectomized immature male Wistar rats using the weight of gastrocnemius and soleus muscles. The weights of ventral prostate and seminal vesicles were used as indicators for androgenic activity. Rats administered 20-HE and TEAD showed a significant increase (p = 0.0006 and p < 0.0001) in the net muscle mass compared to the negative control, while the group receiving TEAD showed the highest percentage among all groups at p < 0.0001. Histopathological investigation of skeletal muscle fibers showed normal morphological structures, and the group administered 20-HE showed an increase in cross sectional area of muscle fibers comparable to methandienone and testosterone groups at p > 0.99. A. dimorphostegia exhibited promising anabolic activity with minimal androgenic side effects.

Effect of intrathecal NIS-lncRNA antisense oligonucleotides on neuropathic pain caused by nerve trauma, chemotherapy, or diabetes mellitus

BackgroundBlocking increased expression of nerve injury-specific long non-coding RNA (NIS-lncRNA) in injured dorsal root ganglia (DRG) through DRG microinjection of NIS-lncRNA small hairpin interfering RNA or generation of NIS-lncRNA knockdown mice mitigates neuropathic pain. However, these strategies are impractical in the clinic. This study employed a Food and Drug Administration (FDA)-approved antisense oligonucleotides strategy to examine the effect of NIS-lncRNA ASOs on neuropathic pain. MethodsEffects of intrathecal injection of NIS-lncRNA antisense oligonucleotides on day 7 or 14 after chronic constriction injury (CCI) of the sciatic nerve, fourth lumbar (L4) spinal nerve ligation, or intraperitoneal injection of paclitaxel or streptozotocin on the expression of DRG NIS-lncRNA and C–C chemokine ligand 2 (CCL2, an NIS-lncRNA downstream target) and nociceptive hypersensitivity were examined. We also assessed whether NIS-lncRNA antisense oligonucleotides produced cellular toxicity. ResultsIntrathecal NIS-lncRNA antisense oligonucleotides attenuated CCI-induced mechanical allodynia, heat hyperalgesia, cold hyperalgesia, and ongoing nociceptive responses, without changing basal or acute nociceptive responses and locomotor function. Intrathecal NIS-lncRNA antisense oligonucleotides also blocked CCI-induced increases in NIS-lncRNA and CCL2 in the ipsilateral L3 and L4 DRG and hyperactivities of neurones and astrocytes in the ipsilateral L3 and L4 spinal cord dorsal horn. Similar results were found in antisense oligonucleotides-treated mice after spinal nerve ligation or intraperitoneal injection of paclitaxel or streptozotocin. Normal morphologic structure and no cell loss were observed in the DRG and spinal cord of antisense oligonucleotides-treated mice. ConclusionThese findings further validate the role of NIS-lncRNA in trauma-, chemotherapy-, or diabetes-induced neuropathic pain and demonstrate potential clinical application of NIS-lncRNA antisense oligonucleotides for neuropathic pain management.

Abscisic acid involved in trehalose improved melon photosynthesis via regulating oxidative stress tolerance and cell morphology structure under cold stress

Melon is a thermophilic vegetable crop with high economic benefits. Cold stress is often encountered in the growth period of melon seedlings in early spring and limits the normal growth and development of seedlings. Exogenous trehalose (Tre) is a green and healthy sugar, known as the ‘sugar of life’, and has a significant role in regulating crop cold tolerance. In this study, we explored whether exogenous Tre induced abscisic acid (ABA) signal involved in regulating melon photosynthesis under cold tolerance and clarified the associated regulatory mechanism. Melon seedlings were pre-treated with nordihydroguaiaretic acid (NDGA), a synthetic inhibitor of the key enzyme 9-cis-epoxycarotenoid dioxygenase for ABA synthesis, followed by spraying with exogenous Tre and then treated with normal temperature or cold stress. Results showed that exogenous Tre induced the up-regulation of CmNCED3 gene expression and increase in ABA level under normal temperature conditions. Cold stress treatment significantly caused leaf membrane lipid peroxidation damage; reduced relative water content, net photosynthetic rate, transpiration rate, stomatal conductance, water use efficiency and the spongy ratio of leaves; caused chloroplast structure damage. The use of NDGA in inhibiting the synthesis of endogenous ABA further aggravated the damages compared with cold treatment alone. Exogenous Tre treatment alleviated the inhibitory effects of cold stress and NDGA and maintained relatively normal cell morphology structure and photosynthesis. Therefore, we speculate that exogenous Tre pretreatment increases the level of endogenous ABA by up-regulating the expression of the CmNCED3 gene and triggers the defence system of melon plants. Under cold stress, cell membrane lipid peroxidation damage in the melon seedlings was significantly reduced by Tre treatment. Meanwhile, the absorption and utilisation of water maintained the relative integrity of the structure and function of mesophyll cells and chloroplasts, thereby reducing the inhibitory effect of cold stress on plant photosynthesis. In conclusion, ABA participates in exogenous Tre-enhanced melon oxidative stress tolerance and alleviation of cell morphology structure damage, which combined to improve melon cold tolerance and photosynthesis. • Exogenous trehalose triggers endogenous ABA levels. • ABA are involved in exogenous Tre-alleviated melon oxidative stress damage. • ABA participate in the Tre-regulated maintenance of cell integrity and function under cold stress.

Impressions of the chronic 900-MHz electromagnetic field in the prenatal period on Purkinje cells in male rat pup cerebella: is it worth mentioning?

The aim of this study was to examine the changes on the Purkinje cells in the cerebella of male rat pups born to pregnant dams that were exposed to an electromagnetic field in the prenatal period. The first stage of the study involved 12 Sprague-Dawley rats, 6 male and 6 female, weighing between 180 and 250 g. The female rats in the experimental group were exposed to a 900-MHz electromagnetic field for 1 h at the same time every day, and no procedure was performed on the control group. Following pregnancy, six male pups from each group were divided into experimental and control groups without any procedure on the pups. After 2 months, they were sacrificed and their cerebella were removed. Histopathologically, following routine processing and fixation procedures, the cerebella were embedded in the tissue blocks. The sections taken from these blocks were stained with cresyl violet. The Purkinje cells in the cerebella were then counted on sections using the optical dissector method on an image analysis system. The estimation of number of the Purkinje cells in the groups revealed more cells in rats in the control group than in the experimental group. Histopathologically, Purkinje cells exhibited a normal morphological structure in the control group, while the cells in the experimental group showed damage. It might be asserted that the exposure of mothers to an electromagnetic field in the prenatal period may affect the development of Purkinje cells in the pup cerebella.

Multi-omics analysis reveals the effects of microbiota on oral homeostasis.

The oral epithelium’s normal morphological structure and function play an important role in maintaining oral homeostasis, among which microbiota and chronic stress are key contributing factors. However, the effects of microbiota and chronic stress on the morphological structures and molecular function of oral homeostasis remain unclear. In this study, morphological staining was used to compare the tongue structure of specific pathogen-free and germ-free mice, and an integrated multi-omics analysis based on transcriptomics, proteomics, and metabolomics was performed to investigate the regulatory mechanisms of microbiota and chronic stress on oral homeostasis. We found that the morphological structure of the tongue in germ-free mice was disordered compared with in specific pathogen-free mice, especially in the epithelium. Multi-omics analysis indicated that differentially expressed molecules of the tongue between germ-free and specific pathogen-free mice were significantly enriched in the mitochondrial metabolic process and immune response. Interestingly, microbiota also significantly influenced the permeability of the oral epithelial barrier, represented by the differential expression of keratinization, and cell adhesion molecules. It was worth noting that the above changes in the tongue between specific pathogen-free and germ-free mice were more significant after chronic stress. Collectively, this is the first study to reveal that the microbiota might maintain oral homeostasis by reshaping the structure of the oral epithelial barrier and changing the function of molecular biology, a process that may be driven by the immune response and mitochondrial metabolic process of oral tissue. Furthermore, chronic stress can enhance the regulatory effects of microbiota on oral homeostasis.

Potential effects of noni (Morinda citrifolia L.) fruits extract against obsessive-compulsive disorder in marble burying and nestlet shredding behavior mice models.

Obsessive-compulsive disorder (OCD) is a chronic and complex psychiatric disorder that usually includes both obsessions and compulsions. Morinda citrifolia L. (Noni) is a functional food and it is a well-known plant due to its potential therapeutic effects on human health in many disorders including neurological and neurodegenerative diseases. The purpose of this study was to evaluate the potential effect of M. citrifolia fruits extract (MCFE) against obsessive-compulsive disorder using the marble burying and nestlet shredding behavior mice models. In addition, brain neurotransmitters such as dopamine (DA), serotonin and noradrenaline (NA) were also assessed. Five mice were placed in each of the different groups, and the treatment was given to the animals for a period of 15 days. The marble burying test was evaluated for 30 min on days 1, 7, and 14 while the nestlet shredding test was evaluated for 60 min on days 2, 8, and 15. Treatments with MCFE (100 and 200 mg/kg, p.o.) significantly improved in both behavior tasks when compared to the control group. In addition, diazepam (2 mg/kg, i.p.) and fluoxetine (15 mg/kg, p.o.) were also significantly improved in both tasks when compared with the control mice. Further locomotor activity study revealed that MCFE and fluoxetine did not affect the locomotor functions when compared to vehicle treated mice. In contrast, diazepam significantly decreased locomotion when compared to the control group. The significant amelioration of biogenic amines were observed in the MCFE-treated animals with increased serotonin levels. The histopathology of the brain, liver, and kidney tissues after MCFE administration revealed normal morphological structure with no signs of toxicity or abnormalities. All these results together suggest that MCFE can be a potential drug candidate for the treatment of OCD. Future research should focus on theidentification and the anti-compulsive activity of the constituents from M. citrifolia.

Prenatal dönemleri boyunca günde bir saat kesintisiz 900 MHz elektromanyetik alan etkisine maruz kalan 75 günlük Sprague Dawley dişi sıçanların böbrek ve mesane dokularının histopatolojik olarak incelenmesi

Amaç: Prenatal dönemde 900 MHz elektromanyetik alan (EMA) maruziyetinin sıçanların postnatal erişkinlik döneminde böbrek ve mesane dokuları üzerine etkileri araştırılmıştır. Gereç ve Yöntem: 18 adet dişi sıçan; kontrol, Sham ve EMA olarak üç gruba ayrıldı. EMA grubu, prenatal dönem boyunca 1 saat/gün 900 MHz EMA'ya maruz bırakıldı; Sham grubu gebe sıçanlar EMA sistemi kapalı kafeste tutuldu. Kontrol grubu gebe sıçanlara ve postnatal yeni doğanlara uygulama yapılmadı. Deney süresi bitiminde böbrek ve mesane dokuları histopatolojik olarak değerlendirildi.Bulgular: Kontrol ve Sham gruplarının böbrek ve mesane örneklerinin normal morfolojide olduğu, EMA grubunda böbrekte tübüler ve glomerular hasar, bowman boşluğunda dilatasyon; mesane ürotelyum epitelinde dejenerasyon izlendi. Sonuç: Prenatal dönemde 900 MHz EMA maruziyeti, erişkinlikte yavru sıçanların böbrek ve mesane dokusunda ciddi histopatolojik değişimlerin olabileceği kanaatindeyiz.

Segmentation of human spermatozoa using improved Havrda-Chavrat entropy-based thresholding method

The assisted method of fertilization has required an identification of sperm cells with normal morphological structure. The abnormal sperm cells cannot provide successful result in artificial fertilization. Nowadays the assessment of morphology of sperm cells is subjective and error prone hence creating automatic evaluation method for morphology assessment, it will improve the success ratio in infertility treatment. The first step in our proposed system is pre-processing where noise removal process is applied on microscopic medical images. In second step, adaptive alpha valued Havrda-Chavrat entropy-based threshold technique is proposed where the maximum probability distribution of foreground pixels or background pixels is assigned to alpha value. Further, existing state-of-art threshold-based segmentation methods are implemented and obtained results on the input images. These segmentation results are compared with the proposed method in terms of supervised and unsupervised evaluation metrics, in which our proposed thresholding method has given optimum threshold value for the segmentation of spermatozoa cells. The outcome of the segmented images and their metric values are indicating better segmentation by our proposed method. Furthermore, this proposed method can be implemented in the mobile applications for diagnosis with artificial intelligence techniques.

Prognostic Value of Hybrid PET/MR Imaging in Patients with Differentiated Thyroid Cancer.

Simple SummaryHybrid positron emission tomography (PET)/magnetic resonance (MR) is an emerging imaging modality with great potential to provide complementary data acquired at the same time, under the same physiological conditions. We evaluated the prognostic value of hybrid 18F-fluorodeoxyglucose (FDG) PET/MR in patients with differentiated thyroid cancer (DTC) who underwent total thyroidectomy and radioactive iodine therapy for suspicion of disease relapse. Our findings suggest that hybrid PET/MR imaging may have the potential to improve the information content of one modality with the other and would offer new opportunities in patients with DTC. However, there is need of more clinical studies to understand the additional value of 18F-FDG PET/MR in patients with DTC.Background: Hybrid positron emission tomography (PET)/magnetic resonance (MR) is an emerging imaging modality with great potential to provide complementary data acquired at the same time, under the same physiological conditions. The aim of this study was to evaluate the prognostic value of hybrid 18F-fluorodeoxyglucose (FDG) PET/MR in patients with differentiated thyroid cancer (DTC) who underwent total thyroidectomy and radioactive iodine therapy for suspicion of disease relapse. Methods: Between November 2015 and February 2017, 55 patients underwent hybrid 18F-FDG PET/MR. Assessment of positive MR was made considering all sequences in terms of malignancy based on the morphological T2-weighted features and the presence of restricted diffusivity on diffusion-weighted imaging images and both needed to be positive on the same lesion. Both foci with abnormal 18F-FDG uptake, which corresponded to tissue abnormalities on the MR, and tracer accumulation, which did not correspond to normal morphological structures, were considered positive. Results: During follow-up (mean 42 ± 27 months), 29 patients (53%) had disease recurrence. In the Cox univariate regression analysis age, serum Tg level ≥ 2 ng/mL, positive short tau inversion recovery (STIR), and positive PET were significant predictors of DTC recurrence. Kaplan–Meier survival analyses showed that patients with Tg ≥ 2 ng/mL had poorer outcomes compared to those with serum Tg level < 2 ng/mL (p < 0.05). Similarly, patients with positive STIR and positive PET had a worst outcome compared to those with negative STIR (p < 0.05) and negative PET (p < 0.005). Survival analysis performed in the subgroup of 36 subjects with Tg level ≥ 2 ng/mL revealed that patients with positive PET had a worst outcome compared to those with negative PET (p < 0.05). Conclusions: Age, serum Tg level ≥ 2 ng/mL, positive STIR, and positive 18F-FDG PET were significant predictors of DTC recurrence. However, the serum Tg level was the only independent predictor of DTC. Hybrid PET/MR imaging may have the potential to improve the information content of one modality with the other and would offer new opportunities in patients with DTC. Thus, further studies in a larger patient population are needed to understand the additional value of 18F-FDG PET/MR in patients with DTC.

Effects of Atractylon on Proliferation and Apoptosis of Intestinal Cancer Cells Through PI3K/AKT/mTOR Signaling Pathway

The study aimed to explore the effects of atractylon on the proliferation and apoptosis of intestinal cancer cells through the phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. The intestinal cancer HT29 cell lines were cultured in vitro, and atractylon at different concentrations (15 and 30 mg/mL) was added. Then cell proliferative activity was detected via cell counting kit-8 (CCK8) assay, and the proportion of positive cells was determined using EdU staining. The content of interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-9 (MMP-9) was detected via enzyme-linked immunosorbent assay (ELISA), and the apoptosis of HT29 cells was detected through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Moreover, reverse transcription-polymerase chain reaction (RT-PCR) was performed to determine the messenger ribonucleic acid (mRNA) levels of proliferation, apoptosis and PI3K/AKT/mTOR signaling pathway-related genes, and Western blotting was used to analyze the expression of the PI3K/AKT/mTOR signaling pathway. The cell growth status was poorer with a lower density in the 15 mg/mL atractylon group and basically normal morphological structure in the 30 mg/mL atractylon group. The number of cells significantly declined and the proliferative activity was also significantly weakened in the 30 mg/mL atractylon group. There were obviously more apoptotic cells in the 30 mg/mL atractylon group. Besides, INF-γ, TNF-α and MMP-9 were all evidently decreased in the 30 mg/mL atractylon group. Expressions of B-cell lymphoma-2 (Bcl-2), PI3K, AKT and mTOR obviously declined in the 30 mg/mL atractylon group, and they were raised in the NC group, while the expression of Caspase3 showed the opposite trends. Atractylon at an appropriate concentration can inhibit the proliferation and promote the apoptosis of intestinal cancer cells by suppressing the PI3K/AKT/mTOR signaling pathway, which can be used to treat colorectal cancer and other related diseases.

Construction of tissue-engineered human corneal endothelium for corneal endothelial regeneration using a crosslinked amniotic membrane scaffold

Descemet's membrane endothelial keratoplasty (DMEK) may provide fast visual rehabilitation in the therapy of corneal endothelial disorders. However, due to shortage of donated corneas, how to construct a corneal endothelial substitute with powerful functions that can be used for DMEK is still unsolved. Herein, we introduced the method of corneal crosslinking (CXL) and conjugated the components of native Descemet's membrane (DM) to improve the mechanical properties and the biocompatibility of denuded amniotic membrane (dAM), further assessed their effects on cell adhesion, proliferation, YAP translocation, and metabolic activity in human corneal endothelial (HCE) cells. Using modified crosslinked dAM (mcdAM) and non-transfected HCE cells, we constructed a tissue-engineered HCE (TE-HCE) and evaluated its functions in cat and monkey models as well. Our results showed that the mechanical properties of mcdAM were improved effectively by CXL, and the adhesion, proliferation, and YAP translocation of HCE cells were dose-dependently improved after ECM modification. The combination of 0.01 mg/mL laminin with 0.1 mg/mL fibronectin showed the highest efficacy. Then, the TE-HCE was constructed in vitro, with a high density of 3612 ± 243 cells/mm2. Results of DMEK in animal models showed that corneal transparency was maintained, accompanied with normal morphology and histological structure of the regenerated corneal endothelium. Therefore, CXL combined with DM-mimic-coating methods could effectively improve the mechanical properties of dAM and enhance the biocompatibility with HCE cells. The constructed TE-HCE had normal histological structure and functioned well in animal models via DMEK, which could be used as a promising powerful equivalent of HCE. Statement of significanceUsing high-quality corneal endothelium and an appropriate endothelial keratoplasty is the most effective way for the treatment of corneal endotheliopathy. Descemet's membrane endothelial keratoplasty (DMEK) which can provide better visual acuity, lower immunological rejection rates, and improved graft survival is an ideal surgery at present. However, due to the shortage of donated corneas, it is urgent to find an equivalent substitute of corneal endothelial donor which is suitable for the DMEK surgery to solve the problem of corneal endothelial regeneration. Herein, we introduced the clinical cornea-crosslinking and Descemet's membrane-mimic-coating methods to build the modified crosslinked denuded amniotic membrane scaffold and further constructed a high-quality corneal endothelial functional substitute that can be used in DMEK surgery.

VDAC1-based peptide as potential treatment for pathologies of the liver and pancreas

Diseases associated with damage to such vital organs of the digestive system as the liver and pancreas are an urgent problem of world health. Non-alcoholic fatty liver disease (NAFLD) is a worldwide epidemic; the problem of type 2 diabetes (T2D) mellitus becomes more acute every year; hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. In spite of progress in identifying risk factors, at the moment there is no generally accepted strategy for a complete cure for these pathologies. Mitochondria, with multiple functions, are key cell organelles. VDAC1, a channel in the outer membrane of mitochondria, is involved in the regulation of cell energy homeostasis, cellular stress, Ca2+ concentration, plays an important role in mitochondria-mediated apoptosis, and also interacts with more than 100 proteins. Numerous channel functions make peptides containing the VDAC1 sequence attractive for therapeutic use. In this article, we consider the VDAC1-based peptide (R-Tf-D-LP4) as a promising method for the treatment of metabolic disorders, and we present possible mechanisms by which the peptide affects the metabolism of fats and carbohydrates. R-Tf-D-LP4 is able to restore normal liver morphology (reducing manifestations of fatty degeneration of hepatocytes, inflammation and fibrosis), is able to slow down the growth of hepatocellular carcinoma by inducing apoptosis and bring blood glucose levels close to normal due to restoration of the normal morphological structure of the pancreas.

Bi-allelic variants in human TCTE1/DRC5 cause asthenospermia and male infertility.

Asthenozoospermia (AZS) is a common male infertility phenotype, accounting for 18% of infertile patients. The N-DRC (Nexin-dynein Regulatory Complex) complex is the motor regulating device in the flagellum, which is found in most eukaryotic organisms with flagellum. The deletion of TCTE1 (T-Complex-Associated Testis-Expressed 1), a component of the N-DRC complex also known as DRC5 (Dynein regulatory complex subunit 5), has been shown to cause asthenospermia in mice. This study mainly introduces a clinical case of male infertility with normal sperm count, normal morphological structure, but low motility and weak forward movement. By whole-exome sequencing, we found that TCTE1 became a frameshift mutant, ENST00000371505.5: c.396_397insTC (p.Arg133Serfs*33), resulting in the rapid degradation of TCTE1 protein and male infertility. This phenotype is similar to the Tcte1-/- (Tcte1 knockout) mice, which showed structural integrity but reduced motility. Further, different from mice, in vitro Fertilization (IVF) could successfully solve the patient's problem of infertility. Our data provides a better understanding of the biological functions of TCTE1 in human flagellum assembly and male fertility.