Research Hub
The living record of
peptide science.
PubMed studies synced daily. Active clinical trials. Evidence updates when the science materially changes. Monthly synthesis for practitioners.
Layer 1
Study feed
Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis.
Brain Sci
Fatima M Shakova, Yuliya I Kirova, Denis N Silachev +2 more
The pharmacological induction and activation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), a key regulator of ischemic brain tolerance, is a promising direction in neuroprotective therapy. Pharmacological agents with known abilities to modulate cerebral PGC-1α are scarce. This study focused on the potential PGC-1α-modulating activity of Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) and Semax (ACTH(4-7) analog) in a rat model of photochemical-induced thrombosis (PT) in the prefrontal cortex. Mexidol (100 mg/kg) was administered intraperitoneally, and Semax (25 μg/kg) was administered intranasally, for 7 days each. The expression of PGC-1α and PGC-1α-dependent protein markers of mitochondriogenesis, angiogenesis, and synaptogenesis was measured in the penumbra via immunoblotting at Days 1, 3, 7, and 21 after PT. The nuclear content of PGC-1α was measured immunohistochemically. The suppression of PGC-1α expression was observed in the penumbra from 24 h to 21 days following PT and reflected decreases in both the number of neurons and PGC-1α expression in individual neurons. Administration of Mexidol or Semax was associated with preservation of the neuron number and neuronal expression of PGC-1α, stimulation of the nuclear translocation of PGC-1α, and increased contents of protein markers for PGC-1α activation. This study opens new prospects for the pharmacological modulation of PGC-1α in the ischemic brain.
Melanotan Tanning Injection: A Rare Cause of Priapism.
Sex Med
Chase W Mallory, Diana M Lopategui, Billy H Cordon
Melanotan II, an injectable melanocortin analog, is illicitly available on the internet to generate a sunless tan through melanocyte induction. It is also used as a sexual stimulant in unlicensed performance enhancement clinics, and has been investigated as a possible treatment agent in erectile dysfunction. We describe in this case report a patient presenting with acute ischemic priapism after subcutaneous injection of melanotan II. The patient was initially managed with cavernosal aspiration and irrigation, and intracavernous injection of phenylephrine without achieving detumescence. After failing initial management, the patient underwent operative management with penoscrotal decompression, a promising alternative technique for the management of refractory ischemic priapism. Priapism after melanotan II injection has only been reported in the literature twice before. This case report highlights a rare presentation of acute ischemic priapism after melanotan II use, managed with surgical decompression. Future therapeutic applications of these agents and updated management guidelines should consider priapism as a possible side effect. CW. Mallory, DM Lopategui, BH. Cordon. Melanotan Tanning Injection: A Rare Cause of Priapism. Sex Med 2021;9:100298.
Repurposing FDA-approved phytomedicines, natural products, antivirals and cell protectives against SARS-CoV-2 (COVID-19) RNA-dependent RNA polymerase.
PeerJ
Mahmoud Kandeel, Yukio Kitade, Abdullah Almubarak
Following the recent emergence of SARS-CoV-2 or coronavirus disease 2019 (COVID-19), drug discovery and vaccine design to combat this fatal infection are critical. In this study, an essential enzyme in the SARS-CoV-2 replication machinery, RNA-dependent RNA polymerase (RDRP), is targeted in a virtual screening assay using a set of 1,664 FDA-approved drugs, including sets of botanical and synthetic derivatives. A set of 22 drugs showed a high docking score of >-7. Notably, approximately one-third of the top hits were either from natural products or biological molecules. The FDA-approved phytochemicals were sennosides, digoxin, asiaticoside, glycyrrhizin, neohesperidin, taxifolin, quercetin and aloin. These approved natural products and phytochemicals are used as general tonics, antioxidants, cell protectives, and immune stimulants (nadid, thymopentin, asiaticoside, glycyrrhizin) and in other miscellaneous systemic or topical applications. A comprehensive analysis was conducted on standard precision and extra precision docking, two-step molecular dynamics simulations, binding energy calculations and a post dynamics analysis. The results reveal that two drugs, docetaxel and neohesperidin, showed strong binding profiles with SARS CoV-2 RdRP. These results can be used as a primer for further drug discovery studies in the treatment of COVID-19. This initiative repurposes safe FDA-approved drugs against COVID-19 RdRP, providing a rapid channel for the discovery and application of new anti-CoV therapeutics.
Review of icatibant use in the Winnipeg Regional Health Authority.
Allergy Asthma Clin Immunol
George Cai, Colin Barber, Chrystyna Kalicinsky
This is a retrospective review of the Winnipeg Regional Health Authority's (WRHA) angioedema patients who were dispensed icatibant in hospital. Icatibant is a bradykinin B2 receptor antagonist indicated for Hereditary Angioedema (HAE) types I and II and is used off-label for HAE with normal C1INH (HAE-nC1INH) and ACE-inhibitor induced angioedema (ACEIIAE). The WRHA's use of icatibant is regulated by the Allergist on call. We characterized icatibant's use and the timeline from patient presentation, compared the real-world experience with the FAST-3 trial and hypothesized the factors which may affect response to icatibant.
Differential Expression and Bioinformatics Analysis of CircRNA in PDGF-BB-Induced Vascular Smooth Muscle Cells.
Front Genet
Jiangtian Tian, Yahong Fu, Qi Li +7 more
Atherosclerosis is mediated by various factors and plays an important pathological foundation for cardiovascular and cerebrovascular diseases. Abnormal vascular smooth muscle cells (VSMCs) proliferation and migration have an essential role in atherosclerotic lesion formation. Circular RNAs (circRNA) have been widely detected in different species and are closely related to various diseases. However, the expression profiles and molecular regulatory mechanisms of circRNAs in VSMCs are still unknown. We used high-throughput RNA-seq as well as bioinformatics tools to systematically analyze circRNA expression profiles in samples from different VSMC phenotypes. Polymerase chain reaction (PCR), Sanger sequencing, and qRT-PCR were performed for circRNA validation. A total of 22191 circRNAs corresponding to 6273 genes (host genes) in the platelet-derived growth factor (PDGF-BB) treated group, the blank control group or both groups, were detected, and 112 differentially expressed circRNAs were identified between the PDGF-BB treated and control groups, of which 59 were upregulated, and 53 were downregulated. We selected 9 circRNAs for evaluation of specific head-to-tail splicing, and 10 differentially expressed circRNAs between the two groups for qRT-PCR validation. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses enrichment analyses revealed that the parental genes of the circRNAs mainly participated in cardiac myofibril assembly and positive regulation of DNA-templated transcription, indicating that they might be involved in cardiovascular diseases. Finally, we constructed a circRNA-miRNA network based on the dysregulated circRNAs and VSMC-related microRNAs. Our study is the first to show the differential expression of circRNAs in PDGF-BB-induced VSMCs and may provide new ideas and targets for the prevention and therapy of vascular diseases.
Neuroprotection by Cerebrolysin and Citicoline Through the Upregulation of Brain-Derived Neurotrophic Factor (BDNF) Expression in the Affected Neural Cells: A Preliminary Clue Obtained Through an In Vitro Study.
Cureus
Anandan P, Santhanam Rengarajan, Sankar Venkatachalam +5 more
Citicoline and cerebrolysin are two unique yet contentious medications because of inconsistencies in efficacy as well as the mystery surrounding their mode of action. The current study aimed to re-validate the neuroprotective benefits of these medications and investigate the possible molecular mechanism.
Effects of low-dose rapamycin on lymphoid organs of mice prone and resistant to accelerated senescence.
Front Immunol
Rafael Dos Santos Barros, Luiz Adriano Damasceno Queiroz, Josiane Betim de Assis +7 more
Aging is a complex, natural, and irreversible phenomenon that subjects the body to numerous changes in the physiological process, characterized by a gradual decline in the organism's homeostatic mechanisms, closely related to immunosenescence. Here, we evaluated the regulation of immunosenescence in lymphoid organs of senescence-accelerated prone 8 (SAM-P8) and senescence-accelerated resistant 1 (SAM-R1) mice treated with a low dose of rapamycin (RAPA). Mice were treated with a dose of 7.1 µg/kg RAPA for 2 months and had body mass and hematological parameters analyzed prior and during treatment. Cellular and humoral parameters of serum, bone marrow, thymus, and spleen samples were evaluated by ELISA, histology, and flow cytometry. Changes in body mass, hematological parameters, cell number, and in the secretion of IL-1β, IL-6, TNF-α, IL-7, and IL-15 cytokines were different between the 2 models used. In histological analyses, we observed that SAM-P8 mice showed faster thymic involution than SAM-R1 mice. Regarding the T lymphocyte subpopulations in the spleen, CD4+ and CD8+ T cell numbers were higher and lower, respectively, in SAM-P8 mice treated with RAPA, with the opposite observed in SAM-R1. Additionally, we found that the low dose of RAPA used did not trigger changes that could compromise the immune response of these mice and the administered dose may have contributed to changes in important lymphocyte populations in the adaptive immune response and the secretion of cytokines that directly collaborate with the maturation and proliferation of these cells.
Rigid-flexible nanocarriers loaded with active peptides for antioxidant and anti-inflammatory applications in skin.
Colloids Surf B Biointerfaces
Yan Wang, Jialiang Lin, Zihao Yu +3 more
Peptides are recognized as highly effective and safe bioactive ingredients. However, t their practical application is limited and hampered by harsh conditions for practical drug delivery. Hence, a novel peptide nanocarrier of copper peptide (GHK-Cu) encapsulation developed by liposome technology combined with the classical Chinese concept of rigidity and flexibility. Different polyols were selected as modification ligands for phospholipid bilayers to construct a nano drug-carrying system with high loading rate, good stability and biocompatibility. In vitro, this complex not only significantly retarded the release ability of copper peptides, but also enabled copper peptides to be effectively resistant to enzymatic degradation. Furthermore, cellular experiments showed that this system mainly regulates Nrf2, SIRT1, and PEG2/COX-2-related signaling pathways, thus effectively counteracting cellular inflammation, senescence, and apoptosis from oxidative damage. Interestingly, a green, non-toxic, efficient and convenient antioxidant system was developed for the prevention and deceleration of skin aging.
Newer pharmacological interventions directed at gut hormones for obesity.
Br J Pharmacol
Michael Camilleri, Andres Acosta
The objective is to review the newer pharmacological interventions for obesity, specifically single, dual and triple incretin receptor agonists that are either available or in the pipeline for treatment of obesity. The three incretin receptor targets are glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and glucagon. There are several approved single or dual incretin agonists which can be administered subcutaneously daily (e.g., liraglutide) or weekly (e.g., semaglutide, dulaglutide, and exenatide QW), and other experimental dual or triple incretin agonists. Analogues of amylin, peptide YY and oxyntomodulin, as well as the combination of a GLP1R agonist and GIPR antagonist also are in development. Oral semaglutide (administered daily) is approved for type 2 diabetes mellitus and is on track for regulatory review for obesity. The review includes specifically perspectives on the effects of these mechanisms and pharmacological agents on gastric emptying, which contribute to satiation and weight loss, in addition to the established evidence on effects on central mechanisms controlling appetite. In the future, it is anticipated that small molecule GLP-1 receptor agonists (e.g., oral danuglipron) will be developed for treating obesity. These pharmacological agents are having significant impact on glycaemic control and obesity and on their co-morbidities.
Low circulating levels of the mitochondrial-peptide hormone SHLP2: novel biomarker for prostate cancer risk.
Oncotarget
Jialin Xiao, Lauren Howard, Junxiang Wan +4 more
Mitochondrial DNA mutations and dysfunction are associated with prostate cancer (PCa). Small humanin-like peptide-2 (SHLP2) is a novel mitochondrial-encoded peptide and an important mitochondrial retrograde signaling molecule.
The whitening effect of cuscutin responsible for traditional use of Bergenia purpurascens.
J Ethnopharmacol
Yang-Yang Liu, Yue Zhang, Ling Jiang +5 more
The roots and rhizomes of Bergenia purpurascens (Hook. f. et Thomson) Engl., was used as a sunscreen to protect against ultraviolet rays in Tibet of China historically, but its skin whitening constituents and pharmacological effects of this plant remained unknown.
Interruption of p38MAPK-MSK1-CREB-MITF-M pathway to prevent hyperpigmentation in the skin.
Int J Biol Sci
Song-Hee Kim, Jiyeon Lee, Jihye Jung +8 more
Background: Melanocortin 1 receptor (MC1R), a receptor of α-melanocyte-stimulating hormone (α-MSH), is exclusively present in melanocytes where α-MSH/MC1R stimulate melanin pigmentation through microphthalmia-associated transcription factor M (MITF-M). Toll-like receptor 4 (TLR4), a receptor of endotoxin lipopolysaccharide (LPS), is distributed in immune and other cell types including melanocytes where LPS/TLR4 activate transcriptional activity of nuclear factor (NF)-κB to express cytokines in innate immunity. LPS/TLR4 also up-regulate MITF-M-target melanogenic genes in melanocytes. Here, we propose a molecular target of antimelanogenic activity through elucidating inhibitory mechanism on α-MSH-induced melanogenic programs by benzimidazole-2-butanol (BI2B), an inhibitor of LPS/TLR4-activated transcriptional activity of NF-κB. Methods: Ultraviolet B (UV-B)-irradiated skins of HRM-2 hairless mice and α-MSH-activated melanocyte cultures were employed to examine melanogenic programs. Results: Topical treatment with BI2B ameliorated UV-B-irradiated skin hyperpigmentation in mice. BI2B suppressed the protein or mRNA levels of melanogenic markers, such as tyrosinase (TYR), MITF-M and proopiomelanocortin (POMC), in UV-B-exposed and pigmented skin tissues. Moreover, BI2B inhibited melanin pigmentation in UV-B-irradiated co-cultures of keratinocyte and melanocyte cells and that in α-MSH-activated melanocyte cultures. Mechanistically, BI2B inhibited the activation of cAMP response element-binding protein (CREB) in α-MSH-induced melanogenic programs and suppressed the expression of MITF-M at the promoter level. As a molecular target, BI2B primarily inhibited mitogen-activated protein kinase (MAPK) kinase 3 (MKK3)-catalyzed kinase activity on p38MAPK. Subsequently, BI2B interrupted downstream pathway of p38MAPK-mitogen and stress-activated protein kinase-1 (MSK1)-CREB-MITF-M, and suppressed MITF-M-target melanogenic genes, encoding enzymes TYR, TYR-related protein-1 (TRP-1) and dopachrome tautomerase (DCT) in melanin biosynthesis, and encoding proteins PMEL17 and Rab27A in the transfer of pigmented melanosomes to the overlaying keratinocytes in the skin. Conclusion: Targeting the MKK3-p38MAPK-MSK1-CREB-MITF-M pathway was suggested as a rationale to inhibit UV-B- or α-MSH-induced facultative melanogenesis and as a strategy to prevent acquired pigmentary disorders in the skin.
Evaluation of the efficacy and safety of a precise thymalfasin-regulated PRaG regimen for advanced refractory solid tumours: protocol for the open-label, prospective, multicentre study (PRaG5.0 study).
BMJ Open
Yuehong Kong, Rongzheng Chen, Meiling Xu +11 more
The PRaG regimen, which consists of hypofractionated radiotherapy combined with a programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitor and granulocyte-macrophage colony stimulating factor (GM-CSF), has been demonstrated to have a survival benefit in patients with advanced solid tumours who have failed at least two lines of treatment. Nonetheless, lymphopenia poses an impediment to the enduring efficacy of PD-1/PD-L1 inhibitor therapy. Adequate lymphocyte reserves are essential for the efficacy of immunotherapy. Coupling the PRaG regimen with immunomodulatory agents that augment the number and functionality of lymphocytes may yield further survival benefits in this cohort of patients.
A systematic review of case series and clinical trials investigating systemic oral or injectable therapies for the treatment of vitiligo.
Skin Res Technol
Alireza Jafarzadeh, Arash Pour Mohammad, Mina Khosravi +4 more
The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine, tofacitinib, baricitinib, corticosteroids, statins, zinc, apremilast, etc., for treating vitiligo lesions.
Inhibition of α-melanocyte-stimulating hormone-induced melanogenesis and molecular mechanisms by polyphenol-enriched fraction of Tagetes erecta L. flower.
Phytomedicine
Sobarathne Senel Sanjaya, Mi Hyeon Park, Wisurumuni Arachchilage Hasitha Maduranga Karunarathne +7 more
The pursuit for safe and efficacious skin-whitening agents has prompted a dedicated exploration of plant-derived compounds. Notably, Tagetes erecta L. flowers have been used as a medicinal extract and possessed in vitro mushroom tyrosinase activity. However, whether polyphenol-enriched fraction extracted from T. erecta L. flowers (TE) regulates melanogenesis within cellular and animal models has not yet been investigated.
Effects of exposure to the neonicotinoid pesticide clothianidin on α-defensin secretion and gut microbiota in mice.
J Vet Med Sci
Sakura Yonoichi, Yukako Hara, Yuya Ishida +14 more
The mechanism by which the neonicotinoid pesticide clothianidin (CLO) disrupts the intestinal microbiota of experimental animals is unknown. We focused on α-defensins, which are regulators of the intestinal microbiota. Subchronic exposure to CLO induced dysbiosis and reduced short-chain fatty acid-producing bacteria in the intestinal microbiota of mice. Levels of cryptdin-1 (Crp1, a major α-defensin in mice) in feces and cecal contents were lower in the CLO-exposed groups than in control. In Crp1 immunostaining, Paneth cells in the jejunum and ileum of the no-observed-adverse-effect-level CLO-exposed group showed a stronger positive signal than control, likely due to the suppression of Crp1 release. Our results showed that CLO exposure suppresses α-defensin secretion from Paneth cells as part of the mechanism underlying CLO-induced dysbiosis.
GDF11 mitigates high glucose-induced cardiomyocytes apoptosis by inhibiting the ALKBH5-FOXO3-CDR1as/Hippo signaling pathway.
Biochim Biophys Acta Mol Cell Res
Yingchun Shao, Mengmeng Li, Yanying Wang +17 more
Diabetic cardiomyopathy remains a formidable health challenge with a high mortality rate and no targeted treatments. Growth differentiation factor 11 (GDF11) has shown promising effects on cardiovascular diseases; however, its role and the underlying mechanism in regulating diabetic cardiomyopathy remain unclear. In this study, we developed mouse models of diabetic cardiomyopathy using leptin receptor-deficient (db/db) mice and streptozocin-induced C57BL/6 mice. The diabetic cardiomyopathy model mice exhibited apparent structural damage in cardiac tissues and a significant increase in the expression of apoptosis-related proteins. Notably, we observed a significant decreased expression of GDF11 in the myocardium of mice with diabetic cardiomyopathy. Moreover, GDF11 cardiac-specific knock-in mice (transgenic mice) exhibited improved cardiac function and reduced apoptosis. Moreover, exogenous administration of GDF11 mitigated high glucose-induced cardiomyocyte apoptosis. Mechanistically, we demonstrated that GDF11 alleviated high glucose-induced cardiomyocytes apoptosis by inhibiting the activation of the alkylation repair homolog 5 (ALKBH5)-forkhead box group O3a (FOXO3)-cerebellar degeneration-related protein 1 transcript (CDR1as)/Hippo signaling pathway. Consequently, this novel mechanism effectively counteracted myocardial cell apoptosis, providing valuable insights into potential therapeutic strategies for clinical diabetic cardiomyopathy.
Dietary regimens appear to possess significant effects on the development of combined antiretroviral therapy (cART)-associated metabolic syndrome.
PLoS One
Boniface M Chege, Peter W Mwangi, Charles G Githinji +1 more
This study investigated the interactions between a low protein high calorie (LPHC) diet and an integrase inhibitor-containing antiretroviral drug regimen (INI-CR)in light of evidence suggesting that the initiation of cART in patients with poor nutritional status is a predictor of mortality independent of immune status.
The in vitro and in vivo depigmentation activity of coenzyme Q0, a major quinone derivative from Antrodia camphorata, through autophagy induction in human melanocytes and keratinocytes.
Cell Commun Signal
You-Cheng Hseu, Jou-Tsen Yeh, Chithravel Vadivalagan +8 more
Coenzyme Q0 (CoQ0), a novel quinone derivative of Antrodia camphorata, has been utilized as a therapeutic agent (including antioxidant, anti-inflammatory, antiangiogenic, antiatherosclerotic, and anticancer agents); however, its depigmenting efficiency has yet to be studied.
Potential Pathways and Pathophysiological Implications of Viral Infection-Driven Activation of Kallikrein-Kinin System (KKS).
Viruses
Sharton Vinícius Antunes Coelho, Fabiane Messner Augusto, Luciana Barros de Arruda
Microcirculatory and coagulation disturbances commonly occur as pathological manifestations of systemic viral infections. Research exploring the role of the kallikrein-kinin system (KKS) in flavivirus infections has recently linked microvascular dysfunctions to bradykinin (BK)-induced signaling of B2R, a G protein-coupled receptor (GPCR) constitutively expressed by endothelial cells. The relevance of KKS activation as an innate response to viral infections has gained increasing attention, particularly after the reports regarding thrombogenic events during COVID-19. BK receptor (B2R and B1R) signal transduction results in vascular permeability, edema formation, angiogenesis, and pain. Recent findings unveiling the role of KKS in viral pathogenesis include evidence of increased activation of KKS with elevated levels of BK and its metabolites in both intravascular and tissue milieu, as well as reports demonstrating that virus replication stimulates BKR expression. In this review, we will discuss the mechanisms triggered by virus replication and by virus-induced inflammatory responses that may stimulate KKS. We also explore how KKS activation and BK signaling may impact virus pathogenesis and further discuss the potential therapeutic application of BKR antagonists in the treatment of hemorrhagic and respiratory diseases.