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12 pages, 449 KiB  
Article
Heterogeneous Transcriptional Landscapes in Human Sporadic Parathyroid Gland Tumors
by Chiara Verdelli, Silvia Carrara, Riccardo Maggiore, Paolo Dalino Ciaramella and Sabrina Corbetta
Int. J. Mol. Sci. 2024, 25(19), 10782; https://doi.org/10.3390/ijms251910782 - 7 Oct 2024
Abstract
The expression of several key molecules is altered in parathyroid tumors due to gene mutations, the loss of heterozygosity, and aberrant gene promoter methylation. A set of genes involved in parathyroid tumorigenesis has been investigated in sporadic parathyroid adenomas (PAds). Thirty-two fresh PAd [...] Read more.
The expression of several key molecules is altered in parathyroid tumors due to gene mutations, the loss of heterozygosity, and aberrant gene promoter methylation. A set of genes involved in parathyroid tumorigenesis has been investigated in sporadic parathyroid adenomas (PAds). Thirty-two fresh PAd tissue samples surgically removed from patients with primary hyperparathyroidism (PHPT) were collected and profiled for gene, microRNA, and lncRNA expression (n = 27). Based on a gene set including MEN1, CDC73, GCM2, CASR, VDR, CCND1, and CDKN1B, the transcriptomic profiles were analyzed using a cluster analysis. The expression levels of CDC73 and CDKN1B were the main drivers for clusterization. The samples were separated into two main clusters, C1 and C2, with the latter including two subgroups of five PAds (C2A) and nineteen PAds (C2B), both differing from C1 in terms of their lower expression of CDC73 and CDKN1B. The C2A PAd profile was also associated with the loss of TP73, an increased expression of HAR1B, HOXA-AS2, and HOXA-AS3 lncRNAs, and a trend towards more severe PHPT compared to C1 and C2B PAds. C2B PAds were characterized by a general downregulated gene expression. Moreover, CCND1 levels were also reduced as well as the expression of the lncRNAs NEAT1 and VLDLR-AS1. Of note, the deregulated lncRNAs are predicted to interact with the histones H3K4 and H3K27. Patients harboring C2B PAds had lower ionized and total serum calcium levels, lower PTH levels, and smaller tumor sizes than patients harboring C2A PAds. In conclusion, PAds display heterogeneous transcriptomic profiles which may contribute to the modulation of clinical and biochemical features. The general downregulated gene expression, characterizing a subgroup of PAds, suggests the tumor cells behave as quiescent resting cells, while the severity of PHPT may be associated with the loss of p73 and the lncRNA-mediated deregulation of histones. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Endocrinology and Metabolism in Italy)
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24 pages, 2563 KiB  
Article
Investigating Non-Native Ribbon Worm Cephalothrix simula as a Potential Source of Tetrodotoxin in British Bivalve Shellfish
by Monika Dhanji-Rapkova, Robert G. Hatfield, David I. Walker, Chantelle Hooper, Sarah Alewijnse, Craig Baker-Austin, Andrew D. Turner and Jennifer M. Ritchie
Mar. Drugs 2024, 22(10), 458; https://doi.org/10.3390/md22100458 - 5 Oct 2024
Viewed by 311
Abstract
Tetrodotoxin (TTX) is a potent marine neurotoxin found in several phylogenetically diverse organisms, some of which are sought as seafood. Since 2015, TTX has been reported in bivalve shellfish from several estuarine locations along the Mediterranean and European Atlantic coasts, posing an emerging [...] Read more.
Tetrodotoxin (TTX) is a potent marine neurotoxin found in several phylogenetically diverse organisms, some of which are sought as seafood. Since 2015, TTX has been reported in bivalve shellfish from several estuarine locations along the Mediterranean and European Atlantic coasts, posing an emerging food safety concern. Although reports on spatial and temporal distribution have increased in recent years, processes leading to TTX accumulation in European bivalves are yet to be described. Here, we explored the hypothesis that the ribbon worm species Cephalothrix simula, known to contain high levels of TTX, could play a role in the trophic transfer of the toxin into shellfish. During a field study at a single location in southern England, we confirmed C. simula DNA in seawater adjacent to trestle-farmed Pacific oysters Magallana gigas (formerly Crassostrea gigas) with a history of TTX occurrence. C. simula DNA in seawater was significantly higher in June and July during the active phase of toxin accumulation compared to periods of either no or continually decreasing TTX concentrations in M. gigas. In addition, C. simula DNA was detected in oyster digestive glands collected on 15 June 2021, the day with the highest recorded C. simula DNA abundance in seawater. These findings show evidence of a relationship between C. simula and TTX occurrence, providing support for the hypothesis that bivalves may acquire TTX through filter-feeding on microscopic life forms of C. simula present in the water column at particular periods each year. Although further evidence is needed to confirm such feeding activity, this study significantly contributes to discussions about the biological source of TTX in European bivalve shellfish. Full article
(This article belongs to the Special Issue Emerging Toxins Accumulation in Shellfish)
14 pages, 1941 KiB  
Article
Umbilical Cord Blood Platelet Lysate Eyedrops for the Treatment of Severe Ocular Surface Disorders in Graft vs. Host Disease Patients: Clinical Study
by Caterina Gagliano, Roberta Foti, Marco Zeppieri, Antonino Maniaci, Salvatore Lavalle, Giuseppa Tancredi, Giuseppe Gagliano, Alessandro Avitabile, Ludovica Cannizzaro and Rosario Foti
Life 2024, 14(10), 1268; https://doi.org/10.3390/life14101268 - 5 Oct 2024
Viewed by 317
Abstract
Background: Graft-versus-host disease (GvHD) is an overactive systemic inflammatory response that can arise following allogeneic hematopoietic stem cell transplantation (HSCT). This condition occurs when the transplanted donor immune cells recognize the recipient’s tissues as foreign and trigger an immune response against them. The [...] Read more.
Background: Graft-versus-host disease (GvHD) is an overactive systemic inflammatory response that can arise following allogeneic hematopoietic stem cell transplantation (HSCT). This condition occurs when the transplanted donor immune cells recognize the recipient’s tissues as foreign and trigger an immune response against them. The ocular surface (eyelids, conjunctiva, meibomian glands, lacrimal glands, and cornea) is particularly involved in GvHD, and its response to existing treatments, including potent immunosuppressants and new targeted therapies, is undesirable, with such treatments often being ineffective. Human allogeneic umbilical cord blood platelet lysate stands out as a potent adjunct to conventional therapies for ocular surface disorders related to severe Dry Eye Disease. This study aimed to evaluate the safety and efficacy of umbilical cord blood platelet lysate eyedrops for the treatment of severe ocular surface disorders in graft-versus-host disease patients who have received previous unsuccessful treatments. Methods: This study was a prospective, non-comparative, interventional case series study involving 22 patients (10 females and 12 males) aged 25–46 years with severe ocular surface disorders that were unresponsive to standard treatments. The GvHD patients were categorized based on the severity of their ocular surface disorders into three groups: Group I: five patients with severe Dry Eye Disease and filamentary keratitis; Group II: eight patients suffering from severe blepharo-kerato-epitheliopathy; Group III: nine patients with corneal ulcers. Fresh umbilical cord blood (UCB) was obtained from healthy donors and subjected to centrifugation using a novel PRP preparation kit provided by Sciacca (AG) Cord blood bank, Italy in a one-step process. In all groups, the outcomes before and after treatment were evaluated by means of the OSDI (Ocular Surface Disease Index), SANDE (Symptom Assessment in Dry Eye) questionnaire, VAS (Visual Analogue Scale), slit lamp examination, Esthesiometry, Lissamine Green Staining, the NIBUT (Non-Invasive Break-Up Time) and BUT, fluorescein staining with digital photography and Oxford classification, the Schirmer Test, the Best Corrected Visual Acuity (BCVA), and Meibography. In Group III at each evaluation time, the size of the ulcer and its relative reduction compared to the baseline size were recorded. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, or pain, were also considered individually. Results: We observed a significant improvement in the SANDE, VAS, and OSDI scores; Schirmer Test; BUT; BCVA; and Oxford classification after treatment with allogeneic cord blood serum eyedrops. Nevertheless, pain and inflammation reduced markedly over time until complete healing in all cases. The mean reduction in the ulcer surface area (compared to baseline values) was significantly higher at all assessment points (p = 0.001 for day 7 and p < 0.001 for subsequent time points every 30 days for 90 days). At the last check-up (after 90 days of treatment), the number of ulcers (Group III, nine patients) with a reduction in size of greater than 50% was eight (88.8%), of which seven ulcers were completely healed. None of the patients experienced treatment-related local or systemic adverse events. In this study, using a relatively large number of cases, we demonstrated that the use of umbilical cord blood platelet lysate eyedrops is a safe, feasible, and effective curative approach for severe ocular surface disease in patients with GvHD. Conclusions: Our pilot study highlights the remarkable effectiveness of allogeneic cord blood serum eyedrops in patients with severe ocular surface disorders following GvHD who have shown an inadequate response to the usual treatments. It is mandatory to design future studies on the efficacy of this therapeutic approach for acute ocular, mucosal, and cutaneous GvHD. Full article
(This article belongs to the Special Issue Eye Manifestations of Systemic Disease, 2nd Edition)
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16 pages, 7894 KiB  
Article
Immunolocalization of Beet Curly Top Virus (BCTV) and GroEL Chaperon Protein of Endosymbionts in Beet Leafhopper (Circulifer tenellus) Vector Tissue
by Batool M. Alkhatib, Samy Belteton and Rebecca Creamer
Viruses 2024, 16(10), 1571; https://doi.org/10.3390/v16101571 - 5 Oct 2024
Viewed by 252
Abstract
Beet curly top virus (BCTV, curtovirus, geminiviridae) causes one of the most economically significant viral diseases in crops in the Western United States and is transmitted only by the beet leafhopper (Circulifer tenellus) in a non-propagative circulative manner. A [...] Read more.
Beet curly top virus (BCTV, curtovirus, geminiviridae) causes one of the most economically significant viral diseases in crops in the Western United States and is transmitted only by the beet leafhopper (Circulifer tenellus) in a non-propagative circulative manner. A better understanding of how this virus overcomes insect vector cellular barriers is essential to understanding virus–vector interactions. The distribution of BCTV in its beet leafhopper vector was investigated using immunofluorescence confocal laser scanning microscope analysis (iCLSM) on the whole-mount-dissected organs of leafhoppers. BCTV was localized in several lobes of the principal salivary glands, filter chamber, anterior midgut, and mid midgut, suggesting the occurrence of midgut and salivary gland barriers to BCTV transmission in its vector C. tenellus. This study also investigated the distribution of the chaperon GroEL homolog protein produced by primary endosymbiotic bacteria within the beet leafhopper, which is believed to indirectly affect viral transmission by enhancing insect immunity and resistance to viruses. GroEL was identified in leafhopper salivary glands lobes, the stylet, salivary canal, the filter chamber, and the Malpighian tubule. This is the first work to visualize the localization of a curtovirus within its beet leafhopper vector. Together, these results can help understand ssDNA virus–vector relationships, including cellular transmission barriers and other vector protein components. Full article
(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)
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13 pages, 568 KiB  
Article
The Prevalence of Sjögren’s Disease in Dental Clinics in the Netherlands Compared with the Prevalence in a Systematic Literature Review of Studies in Other Countries
by Floor Maarse, Jitse F. Huisinga, Derk Hendrik Jan Jager and Henk S. Brand
J. Clin. Med. 2024, 13(19), 5918; https://doi.org/10.3390/jcm13195918 - 3 Oct 2024
Viewed by 561
Abstract
Background/Objectives: Sjögren’s disease (SjD) is an autoimmune disease causing irreversible damage to the exocrine glands but can have symptoms throughout the entire body. The aim of this study is to determine the prevalence of Sjogren’s disease (SjD) in the Netherlands, compare this [...] Read more.
Background/Objectives: Sjögren’s disease (SjD) is an autoimmune disease causing irreversible damage to the exocrine glands but can have symptoms throughout the entire body. The aim of this study is to determine the prevalence of Sjogren’s disease (SjD) in the Netherlands, compare this with the prevalence for other countries in a systematic literature review. Methods: In the first part of this study, the prevalence of SjD was determined at two academic dental clinics in the Netherlands by electronically analysing patient records. In the second part of this study, a systematic literature search was performed in PubMed. Studies in the English language reporting prevalence ratios (PRs), incidence ratios (IRs) or sufficient data to calculate these parameters were included. Population-based studies and population surveys aiming to examine an entire geographic region or using a clearly defined sampling procedure were included. Review studies were excluded. Studies that did not report sufficient data or contained no original data were excluded. Included studies were assessed using the Newcastle–Ottawa assessment scale. Results: At the dental clinic in Amsterdam, 76 SJD patients were identified among a patient population of 81941, resulting in a prevalence ratio of 93 per 100,000 (0.093%) patients. In Nijmegen, 21 SjD patients were identified in a total patient population of 14,240, resulting in a prevalence ratio of 147 per 100,000 (0.15%). Thirty-one studies were included in the systematic review. They varied in diagnostic criteria for SjD with the American-European Consensus Group (AECG) criteria being the most widely used. The reported prevalence ratio varied from 0.008% to 3.3%. The overall pooled prevalence ratio of SjD using the AECG criteria was 0.031%, while the pooled prevalence of SjD using the EU criteria was 0.029%. The overall pooled incidence ratio was 5.2 (95%CI 4.7 to 5.6) per 100,000 person-years. Conclusions: The estimated prevalence ratio of SjD in the Netherlands (0.09% to 0.15%) falls within the worldwide range but is higher than the worldwide pooled prevalence ratio. Full article
(This article belongs to the Special Issue Interaction Between Systemic Diseases and Oral Diseases)
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18 pages, 3487 KiB  
Article
C5a Induces Inflammatory Signaling and Apoptosis in PC12 Cells through C5aR-Dependent Signaling: A Potential Mechanism for Adrenal Damage in Sepsis
by Lucas Mrozewski, Sujeenthar Tharmalingam, Paul Michael, Aseem Kumar and T. C. Tai
Int. J. Mol. Sci. 2024, 25(19), 10673; https://doi.org/10.3390/ijms251910673 - 3 Oct 2024
Viewed by 440
Abstract
The complement system is critically involved in the pathogenesis of sepsis. In particular, complement anaphylatoxin C5a is generated in excess during sepsis, leading to cellular dysfunction. Recent studies have shown that excessive C5a impairs adrenomedullary catecholamine production release and induces apoptosis in adrenomedullary [...] Read more.
The complement system is critically involved in the pathogenesis of sepsis. In particular, complement anaphylatoxin C5a is generated in excess during sepsis, leading to cellular dysfunction. Recent studies have shown that excessive C5a impairs adrenomedullary catecholamine production release and induces apoptosis in adrenomedullary cells. Currently, the mechanisms by which C5a impacts adrenal cell function are poorly understood. The PC12 cell model was used to examine the cellular effects following treatment with recombinant rat C5a. The levels of caspase activation and cell death, protein kinase signaling pathway activation, and changes in inflammatory protein expression were examined following treatment with C5a. There was an increase in apoptosis of PC12 cells following treatment with high-dose C5a. Ten inflammatory proteins, primarily involved in apoptosis, cell survival, and cell proliferation, were upregulated following treatment with high-dose C5a. Five inflammatory proteins, involved primarily in chemotaxis and anti-inflammatory functions, were downregulated. The ERK/MAPK, p38/MAPK, JNK/MAPK, and AKT protein kinase signaling pathways were upregulated in a C5aR-dependent manner. These results demonstrate an apoptotic effect and cellular signaling effect of high-dose C5a. Taken together, the overall data suggest that high levels of C5a may play a role in C5aR-dependent apoptosis of adrenal medullary cells in sepsis. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Pathophysiology of Sepsis)
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10 pages, 1889 KiB  
Case Report
Pleomorphic Parotid Adenoma in a Child Affected with Cri du Chat Syndrome: Clinical, Cytogenetic, and Molecular Analysis
by Cesare Danesino, Federico Biglioli, Laura Moneghini, Roberto Valli, Carla Olivieri, Barbara Testa, Chiara Baldo, Michela Malacarne and Andrea Guala
Int. J. Mol. Sci. 2024, 25(19), 10664; https://doi.org/10.3390/ijms251910664 - 3 Oct 2024
Viewed by 269
Abstract
Salivary gland pleomorphic adenoma (SGPA) is the most common type of benign epithelial tumor; it is observed more commonly in females (with a female-to-male ratio of 1.43:1), and the age at diagnosis ranges between 40 and 59 years, with only 2% of cases [...] Read more.
Salivary gland pleomorphic adenoma (SGPA) is the most common type of benign epithelial tumor; it is observed more commonly in females (with a female-to-male ratio of 1.43:1), and the age at diagnosis ranges between 40 and 59 years, with only 2% of cases diagnosed before age 18. Cri du Chat (CdC) is a rare syndrome caused by deletions of various sizes in the short arm of chromosome 5. Tumors in CdC patients are extremely rare: in Danish, Spanish, Australian, and Japanese groups of cases, no tumors have been reported, while a few cases have been described among 321 CdC patients collected in Italy and Germany. These cases all involve tumors that appear at a young age. We here report the case of a parotid pleomorphic adenoma in an 8-year-old boy with CdC. Exome analysis did not identify variants certainly significant for the development of SGPA. A CGH array, analyzed both in peripheral blood and tumor samples, failed to recognize anomalies previously associated with SGPA but identified a de novo duplication in 7p15.2, which contains part of a gene, SKAP2, in which the increased copy number is associated with the development of a different type of tumor such as pancreatic duct adenocarcinoma. The assumption that the duplication in 7p15.2 is relevant for the development of SGPA in our patient implies that CGH array studies must be included early in life in routine work-ups of CdC to identify CNVs with possible pathogenic roles for tumor development. This is particularly also relevant in relation to the severely impaired possibility for patients with CdC to report discomfort or pain related to tumor development. Constitutional CNVs in addition to the deletion in 5p should also be extensively studied to verify if their presence in some patients could explain why, in these cases, tumors develop at an age younger than expected. Full article
(This article belongs to the Special Issue Genetic Variations in Human Diseases)
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17 pages, 6817 KiB  
Article
Higher Steroid Production in the Right Adrenal Gland Compared to the Left One in db/db Mice, a Model of Type 2 Diabetic Obesity
by Rengui Saxu, Qiming Luo, Yong Yang and Harvest F. Gu
Int. J. Mol. Sci. 2024, 25(19), 10658; https://doi.org/10.3390/ijms251910658 - 3 Oct 2024
Viewed by 225
Abstract
Vertebrates exhibit a left–right asymmetry from the central structures to the peripheral paired endocrine organs. However, the asymmetries in paired endocrine glands and the pathological consequences of such asymmetries remain largely unknown. The adrenal gland constitutes a pair of peripheral end organs in [...] Read more.
Vertebrates exhibit a left–right asymmetry from the central structures to the peripheral paired endocrine organs. However, the asymmetries in paired endocrine glands and the pathological consequences of such asymmetries remain largely unknown. The adrenal gland constitutes a pair of peripheral end organs in the neuroendocrine system, responsible for producing steroid hormones under stimuli. In the present study, the lateralized asymmetry of left and right adrenal glands in leptin receptor-deficit db/db mice was investigated. First, a morphological and histological examination showed that adrenal mass and adrenal cortex volume in db/db mice were significantly higher than in non-diabetic control mice. Then, adrenal transcriptomic and serum metabolomic analyses were performed. Adrenal steroid profiling showed that the levels of corticosterone and aldosterone in the right adrenal gland of db/db mice were two times higher than in the left one. The expression of multiple genes related to adrenal regeneration and innervation in db/db mice was reduced in contrast to the increased steroid hormone secretion. Furthermore, an examination of morphogens in asymmetric adrenal development revealed a significant differential expression of Shh and its receptor gene Ptch1. In conclusion, the present study has provided evidence that a superior steroidogenesis exists in the right adrenal gland of db/db mice and suggested that Shh signaling may play an important role in asymmetric adrenal responses in type 2 diabetes and its complications. Full article
(This article belongs to the Special Issue Developmental Biology: Computational and Experimental Approaches)
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28 pages, 1447 KiB  
Review
Melatonin’s Impact on Wound Healing
by Eun-Hwa Sohn, Su-Nam Kim and Sung-Ryul Lee
Antioxidants 2024, 13(10), 1197; https://doi.org/10.3390/antiox13101197 - 2 Oct 2024
Viewed by 354
Abstract
Melatonin (5-methoxy-N-acetyltryptamine) is an indoleamine compound that plays a critical role in the regulation of circadian rhythms. While melatonin is primarily synthesized from the amino acid tryptophan in the pineal gland of the brain, it can also be produced locally in various tissues, [...] Read more.
Melatonin (5-methoxy-N-acetyltryptamine) is an indoleamine compound that plays a critical role in the regulation of circadian rhythms. While melatonin is primarily synthesized from the amino acid tryptophan in the pineal gland of the brain, it can also be produced locally in various tissues, such as the skin and intestines. Melatonin’s effects in target tissues can be mediated through receptor-dependent mechanisms. Additionally, melatonin exerts various actions via receptor-independent pathways. In biological systems, melatonin and its endogenous metabolites often produce similar effects. While injuries are common in daily life, promoting optimal wound healing is essential for patient well-being and healthcare outcomes. Beyond regulating circadian rhythms as a neuroendocrine hormone, melatonin may enhance wound healing through (1) potent antioxidant properties, (2) anti-inflammatory actions, (3) infection control, (4) regulation of vascular reactivity and angiogenesis, (5) analgesic (pain-relieving) effects, and (6) anti-pruritic (anti-itch) effects. This review aims to provide a comprehensive overview of scientific studies that demonstrate melatonin’s potential roles in supporting effective wound healing. Full article
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29 pages, 2757 KiB  
Article
Effect of Different Early Weaning Diets on Survival, Growth, and Digestive Ontogeny of Channa striatus (Bloch, 1793) Larvae
by Pandi Kalaiselvan, Amit Ranjan, Mir Ishfaq Nazir, Eswaran Suresh, Albin Jemila Thangarani and Kavitha Malarvizhi
Animals 2024, 14(19), 2838; https://doi.org/10.3390/ani14192838 - 1 Oct 2024
Viewed by 369
Abstract
The present study was carried out to evaluate the survival, growth, and digestive ontogeny of C. striatus larvae fed with different experimental diets from 4 days post-hatch (dph) to 32 dph at three-day intervals. A total of 24,000 larvae, with 1600 larvae per [...] Read more.
The present study was carried out to evaluate the survival, growth, and digestive ontogeny of C. striatus larvae fed with different experimental diets from 4 days post-hatch (dph) to 32 dph at three-day intervals. A total of 24,000 larvae, with 1600 larvae per tank in triplicate and an initial mean weight of 0.64 ± 0.01 mg at 4 days post hatch (dph) were subjected to five different early weaning diets, namely Artemia nauplii (T1), co-feed diet comprising Artemia nauplii and formulated micro diet (T2), formulated micro diet (T3), formulated micro diet with protease supplementation (T4), and a commercial diet (T5). All the early weaning diets significantly affected the survival, growth, and ontogeny of the digestive system. Initially at 8 dph, C. striatus fed with T1 showed better survival and growth performance compared to other treatments. By 12 dph, the larvae fed with T1 and T2 showed similar results in terms of survival and growth performance, outperforming other treatments. However, the larvae fed with T2 and T4 outperformed T1 in survival and growth performance at 16 dph. By 24–32 dph, the larvae fed with all treatments met the basic nutritional needs for survival, with T4 fed larvae showing better growth compared to other treatments. At the end of the trial, cumulative mortality was lowest in larvae fed with T1 and highest in the larvae fed with T3 and T5. Similarly, the larvae fed with T4 showed significantly higher weight gain, specific growth rate (SGR), and average daily growth (ADG), while T1 fed larvae exhibited better feed conversion ratio (FCR) and protein efficiency ratio (PER). The enzyme activity fluctuated throughout the experimental duration. Lavae fed with T1 and T2 showed higher enzyme activities initially. However, T4 fed larvae showed higher trypsin and chymotrypsin specific activity at 16 dph along with well-developed intestinal folds with dense microvilli, higher pepsin-specific activity at 20 dph onwards with fully developed gastric glands and thicker gastric mucosal epithelium, and higher amylase and lipase activity at 16 dph with large and prominent zymogen granules in the exocrine pancreas. Peaking at 4 dph, the activity of protein metabolic enzymes (AST and ALT) sharply declined at 8 dph and increased until 32 dph. Larvae fed with T1 showed higher AST and ALT activity along with increased lipid deposits, followed by those fed with T2 and the larvae fed with T4 showing higher activity without fat accumulation but significantly lower than those fed T1 and T2. From the present research findings, it is recommended to initiate weaning for Channa striatus larvae with Artemia nauplii (from 4 dph to 8 dph) followed by a co-feeding regime (Artemia nauplii and formulated diet) between 9 and 16 dph and transition to protease-supplemented micro diet (T4) from 17 dph onwards. Full article
(This article belongs to the Section Aquatic Animals)
8 pages, 1994 KiB  
Article
Effect of Heating and Massaging of Meibomian Glands on Their Imaging
by Justin E. Pettayil, Samya Haque, Mohammed Fardin, Sandeep Kaur Dhallu, Sònia Travé-Huarte, James S. Wolffsohn and Debarun Dutta
Medicina 2024, 60(10), 1603; https://doi.org/10.3390/medicina60101603 - 29 Sep 2024
Viewed by 361
Abstract
Background and Objectives: Infrared light is used to image the Meibomian glands through their thermal profile. This study aimed to investigate the effects of a combination of heating and an eyelid massage on Meibomian gland visibility and tear film parameters. Materials and Methods: [...] Read more.
Background and Objectives: Infrared light is used to image the Meibomian glands through their thermal profile. This study aimed to investigate the effects of a combination of heating and an eyelid massage on Meibomian gland visibility and tear film parameters. Materials and Methods: Twenty-four participants (26 ± 6.9 years) were enrolled in this prospective study, which involved imaging the Meibomian glands of both the lower and upper eyelid and assessing the non-invasive breakup time (NIBUT), tear meniscus height (TMH), and blink rate (using the CA-800, Topcon) at baseline after five minutes of eyelid warming followed by a five-minute eyelid massage. The second session, which was randomised in sequence, repeated the same measurements but without the inclusion of any eyelid warming or massage as the control condition. Results: While there was no change in lower lid Meibomian gland appearance as a result of eyelid heating, eyelid massage, or multiple lid eversion (median 2.0, range 0.0 to 4.0; p = 0.782), there was a change in upper lid appearance 5 min after heating and lid massage (p = 0.025), but again, multiple lid eversion had no effect (p > 0.05). The NIBUT decreased on second lid eversion (p = 0.049), although this was not evident on the third lid eversion (p = 0.090). The effect on NIBUT was also apparent with heating (p = 0.034 immediately after) but was sustained with 5 min of eyelid massage (p = 0.031). The TMH increased with heating (p < 0.001), and this effect was sustained with 5 min of eyelid massage (p = 0.011), but there was no lid eversion effect (p > 0.05). The blink rate was unaffected by heating, eyelid massage, or multiple eversions of the eyelids (median 24 blinks/min, range 8 to 59 blinks/min; p = 0.61). Conclusions: Eyelid warming can increase the visibility of the Meibomian glands, although this effect was only observed with upper lid imaging and the effect dissipated after 5 min of eyelid massage. Warming and massage also disrupt the tear film, as does multiple lid eversion, emphasising the need to use the least invasive tear film assessment techniques first. Full article
(This article belongs to the Section Ophthalmology)
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30 pages, 2014 KiB  
Systematic Review
Postnatal Development of the Circadian Rhythmicity of Human Pineal Melatonin Synthesis and Secretion (Systematic Review)
by Ekkehart Paditz
Children 2024, 11(10), 1197; https://doi.org/10.3390/children11101197 - 29 Sep 2024
Viewed by 461
Abstract
Introduction: According to current knowledge, at birth, the pineal gland and melatonin receptors are already present and the suprachiasmatic nucleus is largely functional, and noradrenaline, the key pineal transmitter, can be detected in the early foetal period. It is still unclear why the [...] Read more.
Introduction: According to current knowledge, at birth, the pineal gland and melatonin receptors are already present and the suprachiasmatic nucleus is largely functional, and noradrenaline, the key pineal transmitter, can be detected in the early foetal period. It is still unclear why the pineal gland is not able to start its own pulsatile synthesis and secretion of melatonin in the first months of life, and as a result, infants during this time are dependent on an external supply of melatonin. Method: The causes and consequences of this physiological melatonin deficiency in human infancy are examined in a systematic review of the literature, in which 40 of 115 initially selected publications were evaluated in detail. The references of these studies were checked for relevant studies on this topic. References from previous reviews by the author were taken into account. Results: The development and differentiation of the pineal gland, the pinealocytes, as the site of melatonin synthesis, and the development and synaptic coupling of the associated predominantly noradrenergic neural pathways and vessels and the associated Lhx4 homebox only occurs during the first year of life. Discussion: The resulting physiological melatonin deficiency is associated with sleep disorders, infant colic, and increased crying in babies. Intervention studies indicate that this deficiency should be compensated for through breastfeeding, the administration of nonpooled donor milk, or through industrially produced chrononutrition made from nonpooled cow’s milk with melatonin-poor day milk and melatonin-rich night milk. Full article
(This article belongs to the Special Issue Current Advances in Paediatric Sleep Medicine)
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22 pages, 9957 KiB  
Article
Loss of CCL28 and CXCL17 Expression and Increase in CCR1 Expression May Be Related to Malignant Transformation of LGBLEL into Lymphoma
by Rui Liu, Mingshen Ma, Jing Li, Fuxiao Luan, Tingting Ren, Nan Wang and Jianmin Ma
Curr. Issues Mol. Biol. 2024, 46(10), 10969-10990; https://doi.org/10.3390/cimb46100652 - 29 Sep 2024
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Abstract
Abstract: To investigate the differential expression of the chemokine signaling pathway in lacrimal gland benign lymphoepithelial lesion (LGBLEL) and lacrimal lymphoma, providing insights into the mechanisms underlying malignant transformation and aiding clinical differentiation. Transcriptome analysis was conducted on patients with LGBLEL, lymphoma, and [...] Read more.
Abstract: To investigate the differential expression of the chemokine signaling pathway in lacrimal gland benign lymphoepithelial lesion (LGBLEL) and lacrimal lymphoma, providing insights into the mechanisms underlying malignant transformation and aiding clinical differentiation. Transcriptome analysis was conducted on patients with LGBLEL, lymphoma, and orbital cavernous hemangioma (CH). Three cases of LGBLEL and three cases of lymphoma were randomly selected as control and experimental groups, respectively. A real-time quantitative polymerase chain reaction (RT-qPCR) was used to validate genes associated with the chemokine signaling pathway. Immunohistochemical (IHC) staining and quantitative Western blotting (WB) were performed for precise protein quantification. Transcriptome analysis revealed differential expression of the chemokine signaling pathway between the LGBLEL and lymphoma groups, identifying ten differentially expressed genes: CCL17, VAV2, CXCR5, NRAS, HCK, RASGRP2, PREX1, GNB5, ADRBK2, and CCL22. RT-qPCR showed that, compared to the lymphoma group, the LGBLEL group had significantly higher expression of CCL28, CXCL17, HCK, GNB5, NRAS, and VAV2 (p = 0.001, <0.001, <0.001, <0.001, =0.020, <0.001, respectively) and lower expression of CCR1 (p = 0.002). IHC staining and quantitative analysis confirmed significant differences in protein expression between the groups for CCL28, CCR1, CXCL17, HCK, GNB5, NRAS, and VAV2 (p = 0.003, 0.011, 0.001, 0.024, 0.005, 0.019, and 0.031, respectively). While IHC provided localization, WB offered greater precision. WB revealed that, compared to the lymphoma group, the LGBLEL group exhibited significantly higher expression of CCL28, CXCL17, HCK, GNB5, NRAS, and VAV2 (p = 0.012, 0.005, 0.009, 0.011, 0.008, and 0.003, respectively) and lower expression of CCR1 (p = 0.014). The chemokine signaling pathway plays a role in the malignant transformation of LGBLEL. The decreased expression of CCL28 and CXCL17, coupled with the increased expression of CCR1, may be linked to the progression of LGBLEL into lymphoma. Full article
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12 pages, 3903 KiB  
Case Report
Personalized Immunotherapy Achieves Complete Response in Metastatic Adenoid Cystic Carcinoma Despite Lack of Conventional Biomarkers
by Ünal Metin Tokat, Ashkan Adibi, Esranur Aydın, Eylül Özgü, Şevval Nur Bilgiç, Onur Tutar, Merve Özbek Doğançay, İrem Demiray and Mutlu Demiray
Curr. Oncol. 2024, 31(10), 5838-5849; https://doi.org/10.3390/curroncol31100434 - 29 Sep 2024
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Abstract
There is currently no effective treatment strategy for recurrent/metastatic adenoid cystic carcinoma (R/M ACC). Furthermore, recent single-agent and combination immunotherapy trials have failed in unselected ACC cohorts, unlike non-ACC salivary gland cancers. Genomic profiling revealed no actionable targets but NOTCH1 and KDM6A frameshift [...] Read more.
There is currently no effective treatment strategy for recurrent/metastatic adenoid cystic carcinoma (R/M ACC). Furthermore, recent single-agent and combination immunotherapy trials have failed in unselected ACC cohorts, unlike non-ACC salivary gland cancers. Genomic profiling revealed no actionable targets but NOTCH1 and KDM6A frameshift and CTCF splice site mutations (no MYB/L fusion) with a low tumor mutational burden (TMB), microsatellite stable (MSS) and negative programmed death ligand 1 (PD-L1) were observed. We recommended an anti-programmed cell death protein 1 (anti-PD-1) plus anti-Cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) combination based on TMB 2-fold greater-than-median TMB in ACC, tumor harboring multiple immunogenic frameshift or splice site mutations, and PD-L1 negativity. Accordingly, we achieved a complete response in a radiotherapy (RT) and chemotherapy (CT)-refractory patient with locally recurrent lacrimal gland (LG) ACC and lung metastasis following personalized immunotherapy in combination with integrative therapeutics. Therefore, it is crucial to assess not only conventional immune biomarkers but also patient-specific parameters, especially in “immune-cold” cancer types. Full article
(This article belongs to the Section Head and Neck Oncology)
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20 pages, 2515 KiB  
Article
Detection of Thymoma Disease Using mRMR Feature Selection and Transformer Models
by Mehmet Agar, Siyami Aydin, Muharrem Cakmak, Mustafa Koc and Mesut Togacar
Diagnostics 2024, 14(19), 2169; https://doi.org/10.3390/diagnostics14192169 - 29 Sep 2024
Viewed by 430
Abstract
Background: Thymoma is a tumor that originates in the thymus gland, a part of the human body located behind the breastbone. It is a malignant disease that is rare in children but more common in adults and usually does not spread outside the [...] Read more.
Background: Thymoma is a tumor that originates in the thymus gland, a part of the human body located behind the breastbone. It is a malignant disease that is rare in children but more common in adults and usually does not spread outside the thymus. The exact cause of thymic disease is not known, but it is thought to be more common in people infected with the EBV virus at an early age. Various surgical methods are used in clinical settings to treat thymoma. Expert opinion is very important in the diagnosis of the disease. Recently, next-generation technologies have become increasingly important in disease detection. Today’s early detection systems already use transformer models that are open to technological advances. Methods: What makes this study different is the use of transformer models instead of traditional deep learning models. The data used in this study were obtained from patients undergoing treatment at Fırat University, Department of Thoracic Surgery. The dataset consisted of two types of classes: thymoma disease images and non-thymoma disease images. The proposed approach consists of preprocessing, model training, feature extraction, feature set fusion between models, efficient feature selection, and classification. In the preprocessing step, unnecessary regions of the images were cropped, and the region of interest (ROI) technique was applied. Four types of transformer models (Deit3, Maxvit, Swin, and ViT) were used for model training. As a result of the training of the models, the feature sets obtained from the best three models were merged between the models (Deit3 and Swin, Deit3 and ViT, Deit3 and ViT, Swin and ViT, and Deit3 and Swin and ViT). The combined feature set of the model (Deit3 and ViT) that gave the best performance with fewer features was analyzed using the mRMR feature selection method. The SVM method was used in the classification process. Results: With the mRMR feature selection method, 100% overall accuracy was achieved with feature sets containing fewer features. The cross-validation technique was used to verify the overall accuracy of the proposed approach and 99.22% overall accuracy was achieved in the analysis with this technique. Conclusions: These findings emphasize the added value of the proposed approach in the detection of thymoma. Full article
(This article belongs to the Special Issue Advanced Computer-Aided Diagnosis Using Medical Images)
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