The introduction of peptide receptor radionuclide therapy (PRRT) to the Philippines has allowed for novel approaches in the management of neuroendocrine tumors (NETs). This case report details the management of a 66-year-old Filipino man diagnosed with metastatic pancreatic NET after biopsy and staging with Ga-68 DOTATATE PET-CT. After poor response to somatostatin analogue therapy, the patient was advised to undergo PRRT. Upon completing four cycles of PRRT with Lu-177 DOTATATE, the metastatic hepatic lesions showed resolution and the pancreatic tail tumor exhibited regression, allowing the patient to undergo surgical resection of the primary tumor. On follow-up, he was declared to be in remission with good quality of life and no imaging evidence of recurrence. The case underscores the diagnostic and therapeutic utility of radiolabeled somatostatin analogues along with the importance of a multidisciplinary approach in the management of an initially unresectable metastatic pancreatic NET
Receptors, Peptide ; Pancreatic Neoplasms ; Neuroendocrine Tumors

Peptide dual agonists toward both glucagon-like peptide 1 receptor (GLP-1R) and glucagon receptor (GCGR) are emerging as novel therapeutics for the treatment of type 2 diabetes mellitus (T2DM) patients with obesity. Our previous work identified a Xenopus GLP-1-based dual GLP-1R/GCGR agonist termed xGLP/GCG-13, which showed decent hypoglycemic and body weight lowering activity. However, the clinical utility of xGLP/GCG-13 is limited due to its short in vivo half-life. Inspired by the fact that O-GlcNAcylation of intracellular proteins leads to increased stability of secreted proteins, we rationally designed a panel of O-GlcNAcylated xGLP/GCG-13 analogs as potential long-acting GLP-1R/ GCGR dual agonists. One of the synthesized glycopeptides 1f was found to be equipotent to xGLP/GCG-13 in cell-based receptor activation assays. As expected, O-GlcNAcylation effectively improved the stability of xGLP/GCG-13 in vivo. Importantly, chronic administration of 1f potently induced body weight loss and hypoglycemic effects, improved glucose tolerance, and normalized lipid metabolism and adiposity in both db/db and diet induced obesity (DIO) mice models. These results supported the hypothesis that glycosylation is a useful strategy for improving the in vivo stability of GLP-1-based peptides and promoted the development of dual GLP-1R/GCGR agonists as antidiabetic/antiobesity drugs.
Mice ; Animals ; Glucagon-Like Peptide 1/metabolism* ; Receptors, Glucagon/therapeutic use* ; Xenopus laevis/metabolism* ; Diabetes Mellitus, Type 2/drug therapy* ; Glycopeptides/therapeutic use* ; Obesity/drug therapy* ; Hypoglycemic Agents/pharmacology* ; Peptides/pharmacology*

Elabela is a newly discovered peptide in recent years.It is the endogenous ligand of Apelin receptor(APJ)and plays an important role in embryonic development and adult organs.Elabela-APJ axis is closely related to organ fibrosis.Elabela can protect the functions of heart and kidney by antagonizing renin-angiotensin system and regulating blood pressure.In addition,it can prevent kidney and heart fibrosis by down-regulating the expression of fibrosis and inflammatory factors.However,there is a positive correlation between the level of Elabela and the degree of liver fibrosis,suggesting that Elabela may play a role in promoting liver fibrosis.This review aims to explore the role of Elabela-APJ axis in renal fibrosis,cardiac fibrosis,and liver fibrosis,and to provide a new therapeutic target for organ fibrosis.
Apelin ; Apelin Receptors ; Blood Pressure ; Female ; Fibrosis ; Humans ; Peptide Hormones ; Pregnancy

OBJECTIVE: To explore the clinical characteristics and genetic basis for a pair of twins affected with hyaline fibromatosis syndrome (HFS). METHODS: Clinical data of the twins were retrospectively analyzed. High-throughput sequencing was carried out to detect potential pathogenic variants. CLUSTALX was employed to analyze cross-species conservation of the mutant amino acids. Impact of the mutations was predicted by using software including PolyPhen-2 and Mutation taster. RESULTS: The pair of twins have featured growth and intelligence retardation, and were found to carry compound heterozygous variants of the ANTXR2 gene including c.1214G>A and c.1074delT, among which c.1214G>A was unreported previously. Both variants were predicted to be pathogenic. In addition to growth and mental delay, the pair of twins also featured hyperplasia of the gum and soft tissue-like masses of the auricle. The younger brother had rupture of the auricle mass during follow-up. CONCLUSION The patients' condition can probably be attributed to the compound heterozygous variants of the ANTXR2 gene. Above finding has facilitated molecular diagnosis of the patients.
Asian Continental Ancestry Group/genetics* ; China ; Humans ; Hyalinosis, Systemic/genetics* ; Male ; Mutation ; Pedigree ; Receptors, Peptide/genetics* ; Retrospective Studies

OBJECTIVE: To investigate the clinical value of expression level of interleukin-2 receptor (IL-2R) and interleukin-8 (IL-8) in the fever patients with hematological malignancies. METHODS: A total of 121 inpatients in the First Affiliated Hospital of Anhui Medical University from April 2018 to October 2019 were enrolled in this study. The patients were separated into infection group (61 cases) and non-infection group (60 cases). In the meantime, 40 healthy people without fever or infection in the hospital for physical examination were set as matched group. C-reactive protein (CRP), procalcitonin (PCT), and cytokines were detected in all the patients with fever after admission and infection control. While, blood samples were taken from healthy people during physical examination. RESULTS: The expression levels of IL-2R in infection group were higher than those in the control group (P<0.001), and the level of serum IL-2R in infection group was also higher than that in the non-infection group (P<0.05). Based on Spearman analysis, in patients with malignant hematologic disease, serum IL-2R level was positively correlated with CRP (r=0.557, P<0.001) and IL-8 (r=0.479, P<0.001), and IL-8 level was positively correlated with CRP (r=0.318, P<0.001). Compared with the non-infection group, the area under the curve (AUC) for the level of CRP, PCT, and IL-2R of the infection group was 0.714 (95%CI: 0.623-0.806), 0.765 (95%CI: 0.680-0.851), and 0.761 (95%CI: 0.686-0.836), the sensitivity was 0.705, 0.852, and 0.705, and the specificity was 0.717, 0.70, and 0.60, respectively. While, AUC of CRP+PCT, CRP+IL-2R, PCT+IL-2R, and CRP+PCT+IL-2R was 0.789 (95%CI: 0.712-0.866), 0.702 (95%CI: 0.623-0.782), 0.757 (95%CI: 0.677-0.838), and 0.789 (95%CI: 0.712-0.866), the sensitivity was 0.738, 0.934, 0.705, and 0.738, and the specificity was 0.840, 0.470, 0.810, and 0.840, respectively. CONCLUSION CRP, PCT, IL-2R, and IL-8 are useful parameters for diagnosis of the infectious fever in patients with hematological malignancies, which provides the basis of initial diagnosis and rational use of antibioties for clinician.
Biomarkers ; C-Reactive Protein ; Calcitonin ; Calcitonin Gene-Related Peptide ; Hematologic Neoplasms ; Humans ; Interleukin-8 ; Protein Precursors ; Receptors, Interleukin-2 ; Sepsis

Objective: To explore the effects of the mu-opioid receptor (MOR) in the paraventricular nucleus (PVN) on the ejaculatory behaviors of male rats and its potential mechanisms. METHODS: Male SD rats with normal ejaculation ability were mated with female ones in hormone-induced estrus. After bilateral PVN microinjection of D-Ala-2-Me-Phe-4-Gly-ol enkephalin (DAGO) or D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) with an inserted catheter, the male animals were observed for mount latency (ML), mount frequency (MF), intromission latency (IL), intromission frequency (IF), ejaculation latency (EL), ejaculation frequency (EF), post-ejaculation interval (PEI), and intromission ratio (IR). The lumbar sympathetic nerve activity (LSNA) of the rats was recorded using the PowerLab data acquisition hardware device, and the levels of norepinephrine (NE) in the peripheral plasma were measured by ELISA following microinjection of saline or different doses of DAGO or CTAP. RESULTS: Neither CTAP nor DGAO significantly affected the ML of the male rats (P > 0.05). DGAO remarkably increased IF (P < 0.01) and MF (P < 0.01), prolonged IL (P < 0.01), EL (P < 0.01) and PEI (P < 0.01), and reduced EF (P <0.01) and IR (P < 0.05). On the contrary, CTAP markedly decreased IF (P < 0.01) and MF (P < 0.01), shortened IL (P < 0.01), EL (P < 0.01) and PFI (P < 0.01), and elevated EF (P < 0.01) and IR (P < 0.01). Additionally, DAGO decreased LSNA in a dose-dependent manner and reduced the NE level in the peripheral plasma. CTAP, however, not only offset the effects of DAGO on LSNA, but also significantly increased LSNA. CONCLUSIONS MOR in PVN inhibits ejaculatory behaviors in male rats by weakening LSNA, which has provided some theoretical evidence for the use of highly selective opioids in the treatment of premature ejaculation.
Animals ; Ejaculation ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology* ; Female ; Male ; Paraventricular Hypothalamic Nucleus/physiology* ; Peptide Fragments/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, mu/physiology* ; Somatostatin/pharmacology* ; Sympathetic Nervous System/physiology*

Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms arising from the pancreatic islet of Langerhans and can be functioning or non-functioning based on the clinical symptoms caused by hormonal secretions. PNETs are the second most common tumor of the pancreas and represent 1–2% of all pancreatic neoplasms. The incidence of pNETs appears to be rising and the prognosis seems to be improving, likely due to the improved treatment options. Recent updates of the World Health Organization classification and grading separate pNETs into 2 broad categories according to the histopathologic criteria, including the Ki-67 proliferative index and mitotic counts: well-differentiated NET and poorly-differentiated neuroendocrine carcinoma (NEC). The classification also incorporates a new subcategory of well-differentiated high-grade NEC (grade 3) to the well-differentiated NET category. This new classification algorithm aims to improve the prediction of the clinical outcomes and survival and help clinicians select better therapeutic strategies for patient care and management. The treatment of advanced or metastatic pNETs may include surgical resection, liver-directed therapies, and/or systemic treatments. In unresectable patients, the goals of these therapies are to palliate the tumor-related symptoms and prolong the lifespan. Systemic therapy consists of the following broad modalities: somatostatin analogues, molecular targeted therapy, systemic chemotherapy, and peptide receptor radionuclide therapy. In conclusion, pNETs are diagnosed increasingly throughout the world, usually with metastatic disease and requiring systemic therapy. Each patient should be evaluated thoroughly and discussed individually by a multidisciplinary and dedicated NET-expert team, which might consider all treatment options, including ongoing clinical trials before selecting the appropriate treatment sequence.
Carcinoma, Neuroendocrine ; Classification ; Drug Therapy ; Humans ; Incidence ; Islets of Langerhans ; Molecular Targeted Therapy ; Neuroectodermal Tumors, Primitive ; Neuroendocrine Tumors ; Pancreas ; Pancreatic Neoplasms ; Patient Care ; Prognosis ; Receptors, Peptide ; Somatostatin ; World Health Organization

PURPOSE: This study investigated the role of natriuretic peptide receptor 2 (NPR2) on cell proliferation and testosterone secretion in mouse Leydig cells. MATERIALS AND METHODS: Mouse testis of different postnatal stages was isolated to detect the expression C-type natriuretic peptide (CNP) and its receptor NPR2 by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Leydig cells isolated from mouse testis were cultured and treated with shNPR2 lentiviruses or CNP. And then the cyclic guanosine monophosphate production, testosterone secretion, cell proliferation, cell cycle and cell apoptosis in mouse Leydig cells were analyzed by ELISA, RT-qPCR, Cell Counting Kit-8, and flow cytometry. Moreover, the expression of NPR2, cell cycle, apoptosis proliferation and cell cycle related gene were detected by RT-qPCR and Western blot. RESULTS: Knockdown of NPR2 by RNAi resulted in S phase cell cycle arrest, cell apoptosis, and decreased testosterone secretion in mouse Leydig cells. CONCLUSIONS: Our study provides more evidences to better understand the function of CNP/NPR2 pathway in male reproduction, which may help us to treat male infertility.
Animals ; Apoptosis ; Blotting, Western ; Cell Count ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Proliferation ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Germ Cells ; Guanosine Monophosphate ; Humans ; Infertility, Male ; Lentivirus ; Leydig Cells ; Male ; Mice ; Natriuretic Peptide, C-Type ; Polymerase Chain Reaction ; Receptors, Peptide ; Reproduction ; Reverse Transcription ; RNA Interference ; S Phase ; Testicular Diseases ; Testis ; Testosterone

Rodent MrgC receptor (Mas-related G-protein-coupled receptor subtype C) shares 65% sequence homology and similarities in terms of expression pattern and binding profile with human Mas-related gene X receptor 1 (hMrgX1). Therefore, researchers generally explore the role of hMrgX1 by studying the function of MrgC receptor. Murine MrgC receptor is uniquely expressed in small-diameter neurons of dorsal root ganglia (DRG) and trigeminal ganglia (TG), which is closely related to the transmission process of pain. This review summarizes the analgesic effects of intrathecal activation of MrgC receptors in pathological pain and morphine tolerance.
Animals ; Drug Tolerance ; Ganglia, Spinal ; Humans ; Mice ; Morphine ; pharmacology ; Pain ; Peptide Fragments ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; physiology ; Trigeminal Ganglion

IL-18 is a crucial pro-inflammatory cytokine that mediates chronic intestinal inflammation. Metformin, an anti-diabetic drug, was reported to have ameliorative effects on inflammatory bowel disease. Recently, the mechanism of action of metformin was explained as a modulation of gut microbiota. In this study, fecal microbiota transplantation (FMT) using fecal material from metformin-treated mice was found to upregulate the expression of GLP-1 and pattern-recognition receptors TLR1 and TLR4 for the improvement in hyperglycemia caused by a high-fat diet. Further, FMT downregulated the expression of the inflammatory cytokine IL-18. Within the genera Akkermansia, Bacteroides, and Butyricimonas, which were promoted by metformin therapy, Butyricimonas was found to be consistently abundant following FMT. Our findings suggest that modulation of gut microbiota is a key factor for the anti-inflammatory effects of metformin which is used for the treatment of hyperglycemia.
Animals ; Bacteroides ; Diet, High-Fat ; Down-Regulation ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Glucagon-Like Peptide 1 ; Hyperglycemia ; Inflammation ; Inflammatory Bowel Diseases ; Interleukin-18 ; Metformin ; Mice ; Toll-Like Receptors