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Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy.
Proc Natl Acad Sci U S A
Hiroto Ito, Noriaki Fukatsu, Sheikh Mizanur Rahaman +5 more
Narcolepsy is a sleep disorder caused by deficiency of orexin signaling. However, the neural mechanisms by which deficient orexin signaling causes the abnormal rapid eye movement (REM) sleep characteristics of narcolepsy, such as cataplexy and frequent transitions to REM states, are not fully understood. Here, we determined the activity dynamics of orexin neurons during sleep that suppress the abnormal REM sleep architecture of narcolepsy. Orexin neurons were highly active during wakefulness, showed intermittent synchronous activity during non-REM (NREM) sleep, were quiescent prior to the transition from NREM to REM sleep, and a small subpopulation of these cells was active during REM sleep. Orexin neurons that lacked orexin peptides were less active during REM sleep and were mostly silent during cataplexy. Optogenetic inhibition of orexin neurons established that the activity dynamics of these cells during NREM sleep regulate NREM-REM sleep transitions. Inhibition of orexin neurons during REM sleep increased subsequent REM sleep in "orexin intact" mice and subsequent cataplexy in mice lacking orexin peptides, indicating that the activity of a subpopulation of orexin neurons during the preceding REM sleep suppresses subsequent REM sleep and cataplexy. Thus, these results identify how deficient orexin signaling during sleep results in the abnormal REM sleep architecture characteristic of narcolepsy.
A preliminary study investigating the clinical potential of measuring cerebrospinal-fluid lactate levels in patients with narcolepsy type 1 and 2.
Physiol Behav
Mariana Fernandes, Matteo Spanetta, Fabio Placidi +6 more
Besides the quantification of orexin-A/hypocretin-1 cerebrospinal fluid (CSF) levels in narcolepsy for diagnostic purposes, several other CSF biomarkers have been evaluated, although with controversial results. Since CSF lactate concentrations fluctuate according to the sleep-wake cycle with higher levels during wakefulness and lower levels during sleep, as documented in animal model studies, the present study aimed at quantifying the CSF lactate levels in patients with narcolepsy type 1 (NT1) and 2 (NT2), which are two sleep disorders featured by excessive daytime sleepiness (EDS).
Differential impact of a ghrelin receptor antagonist or inverse agonist in the electrical kindling model of epilepsy.
Epilepsy Res
Siamak Beheshti, Shiva Ershadi, Fatemeh Zamani +2 more
Ghrelin is a peptide, which has been shown to affect seizures. However, there is not a consensus about its real impact on the control of seizure severity. We assessed the influence of intra-amygdala injections of a ghrelin receptor (GHSR) antagonist, as well as a GHSR inverse agonist on the electrical kindling-induced seizures. Two unipolar electrodes and a tripolar electrode twisted with a guide cannula were implanted in the skull surface or the basolateral amygdala of adult male rats, respectively. A rapid electrical kindling protocol was applied for kindling epileptogenesis. The stimulations were applied until rats showed three consecutive stage five seizures. Each rat was considered as its control. D-Lys-3-GHRP-6 (1, 12.5, and 25 μg/rat) or [D-Arg, D-phe, D-Trp, heu] substance P (D-SP) (50, 500 and 5000 ng/rat) as the GHSR antagonist or inverse agonist were injected into the basolateral amygdala. Seizure parameters including after-discharge duration (ADD), stage five duration (S5D), and seizure stage (SS) were documented thirty minutes following administration of the drugs or saline. Antagonism of the GHSR in the amygdala, significantly increased seizure induction in the kindled rats, in a dose-dependent manner, and induced spontaneous seizures leading to status epilepticus. Conversely, D-SP had a dose-dependent anticonvulsant activity, indicated by decreased ADD and S5D. The results show that GHSR inverse agonism suppressed seizure severity in the rat amygdala kindling model, whereas GHSR antagonism made seizures more severe. Therefore, when considering the ghrelin system to modulate seizures, it is crucial to note the differential impact of various GHSR ligands.
Combined GLP-1 Receptor Agonist and Amylin Analogue Pharmacotherapy to Treat Obesity Comorbid With Type 1 Diabetes.
JCEM Case Rep
Gunther Wong, Erica M Garner, Gitanjali Srivastava
Type 1 diabetes mellitus (T1DM) with obesity is increasingly common, prompting effective clinical interventions to induce weight loss in this population. We present 3 patients with T1DM and obesity prescribed a glucagon-like peptide 1 receptor agonist (GLP-1RA) and pramlintide. Case 1: A 32-year-old male with obstructive sleep apnea (OSA) who lost -20.9 kg (-16.1% of total body weight [TBW]) over 10 months on semaglutide and pramlintide. Case 2: A 68-year-old female with diabetic retinopathy, coronary artery disease, hypertension, hypothyroidism, and depression/anxiety initially treated with topiramate, losing -8.4 kg, but experiencing weight plateau. After adding dulaglutide and pramlintide, she lost an additional -12.8 kg (-14.0% TBW) over 7 months, with total weight loss of -21.2 kg (-23.1% TBW). Case 3: A 49-year-old female with hypertension, hypothyroidism, and depression who lost -14.6 kg (-17.9% TBW) over 6 months on semaglutide and pramlintide. No significant side effects were experienced. All patients reported decreased insulin requirements on pramlintide, and hemoglobin A1c levels remained constant or decreased throughout the treatment period. Pramlintide and GLP-1RA resulted in excellent weight loss in our patients with obesity and T1DM. This combination may have a synergistic effect on the gut-brain axis. More research is required to substantiate these findings.
[Cognitive impairment and tactics of using the drug Cerebrolysin. Resolution of the International Council of Experts (May 12, 2023)].
Zh Nevrol Psikhiatr Im S S Korsakova
O S Levin, I A Voznyuk, S N Illarioshkin +11 more
The aging of the population and the associated increase in the share of cognitive impairments in the structure of a wide range of diseases are a serious challenge for modern healthcare. Difficulties in the treatment of cognitive disorders are determined by many factors, including the age of patients, comorbidity, forced polypragmasia and the adequacy of the dosage of drugs that restore cognitive activity. The experts discussed information about the therapeutic potential of the drug Cerebrolysin in the treatment of cognitive disorders of various origins, stated significant experience of its effective and safe use in many clinical studies in mild and moderate forms of dementia. At the same time, there was a lack of consistent and systematic data on the dosage regimen, frequency, and duration of use of the drug in different forms of cognitive impairment and the degree of their severity. The aim of the international council of experts was to determine the optimal dosage regimens of the drug Cerebrolysin in patients with various etiologies and severity of cognitive impairment. The result of the work was the approval of a unified scheme for the use of the drug Cerebrolysin, considering the severity of the disease and its duration.
The Potential Use of Carnosine in Diabetes and Other Afflictions Reported in Long COVID Patients.
Front Neurosci
Fabiola Cardoso Diniz, Alan Roger Hipkiss, Gustavo Costa Ferreira
Carnosine is a dipeptide expressed in both the central nervous system and periphery. Several biological functions have been attributed to carnosine, including as an anti-inflammatory and antioxidant agent, and as a modulator of mitochondrial metabolism. Some of these mechanisms have been implicated in the pathophysiology of coronavirus disease-2019 (COVID-19). COVID-19 is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The clinical manifestation and recovery time for COVID-19 are variable. Some patients are severely affected by SARS-CoV-2 infection and may experience respiratory failure, thromboembolic disease, neurological symptoms, kidney damage, acute pancreatitis, and even death. COVID-19 patients with comorbidities, including diabetes, are at higher risk of death. Mechanisms underlying the dysfunction of the afflicted organs in COVID-19 patients have been discussed, the most common being the so-called cytokine storm. Given the biological effects attributed to carnosine, adjuvant therapy with this dipeptide could be considered as supportive treatment in patients with either COVID-19 or long COVID.
Thymosin α1 modulated the immune landscape of COVID-19 patients revealed by single-cell RNA and TCR sequencing.
Int Immunopharmacol
Han Bai, Liyuan Liang, Xin Qi +9 more
The Coronavirus disease-19 (COVID-19) pandemic has posed a serious threat to global health. Thymosin α1 (Tα1) was considered to be applied in COVID-19 therapy. However, the data remains limited.
A retrospective study of Cerebrolysin in patients with moderate to severe traumatic brain injury: Cognitive and functional outcomes.
J Med Life
Claudio Soto, Pablo Salinas, Daniel Muñoz +4 more
In this retrospective study, we aimed to evaluate the effects of the neurotrophic compound Cerebrolysin on executive, cognitive, and functional performance in patients with traumatic brain injury (TBI) with a highly severe disability level. A total of 44 patients were included in the study, with 33 patients in the control group and 11 patients in the interventional group who received intravenous infusions of 30 mL Cerebrolysin. Both groups received standard rehabilitation therapy following the rehabilitation protocol for patients with TBI at Hospital Clínico Mutual de Seguridad. Functional and cognitive scales were evaluated at baseline, at four months, and at the endpoint of the intervention therapy at seven months (on average). The results revealed a significant improvement in the Cerebrolysin-treated group compared to the control group. Specifically, patients who received Cerebrolysin showed a moderate residual disability and a significant reduction in the need for care. Concerning the promising results and considering the limitations of the retrospective study design, we suggest that randomized controlled studies be initiated to corroborate the positive findings for Cerebrolysin in patients with moderate to severe brain trauma.
Liposomes as Carriers of GHK-Cu Tripeptide for Cosmetic Application.
Pharmaceutics
Michał Dymek, Karolina Olechowska, Katarzyna Hąc-Wydro +1 more
Liposomes are self-assembled spherical systems composed of amphiphilic phospholipids. They can be used as carriers of both hydrophobic and hydrophilic substances, such as the anti-aging and wound-healing copper-binding peptide, GHK-Cu (glycyl-L-histidyl-L-lysine). Anionic (AL) and cationic (CL) hydrogenated lecithin-based liposomes were obtained as GHK-Cu skin delivery systems using the thin-film hydration method combined with freeze-thaw cycles and the extrusion process. The influence of total lipid content, lipid composition and GHK-Cu concentration on the physicochemical properties of liposomes was studied. The lipid bilayer fluidity and the peptide encapsulation efficiency (EE) were also determined. Moreover, in vitro assays of tyrosinase and elastase inhibition were performed. Stable GHK-Cu-loaded liposome systems of small sizes (approx. 100 nm) were obtained. The bilayer fluidity was higher in the case of cationic liposomes. As the best carriers, 25 mg/cm3 CL and AL hydrated with 0.5 mg/cm3 GHK-Cu were selected with EE of 31.7 ± 0.9% and 20.0 ± 2.8%, respectively. The obtained results confirmed that the liposomes can be used as carriers for biomimetic peptides such as copper-binding peptide and that the GHK-Cu did not significantly affect the tyrosinase activity but led to 48.90 ± 2.50% elastase inhibition, thus reducing the rate of elastin degeneration and supporting the structural integrity of the skin.
Cationic exchange SPE combined with triple quadrupole UHPLC-MS/MS for detection of GHRHs in urine samples.
Anal Biochem
Cătălina-Diana Cristea, Mihai Radu, Ani Toboc +2 more
The use of growth hormone-releasing hormones (GHRHs) is prohibited in sports according to the regulations of the World Anti-Doping Agency (WADA). Considering the complexity of urine samples and the low concentrations at which these analytes should be detected, analyzing GHRHs is a challenging task. In most of the studies, GHRHs are analyzed using UHPLC-HRMS with an orbitrap. The present developed and validated method for some GHRHs (tesamorelin, CJC-1295, sermorelin (GRF 1-29), sermorelin (3-29)-NH2, somatorelin) is based on the triple quadrupole UHPLC/MS-MS method with solid phase extraction (SPE) with weak cation exchange and is able to detect concentrations as low as 0.2 ng/mL (LOD), a limit of quantification (LOQ) at 0.6 ng/mL, and linearity across the range of 0.1 ng/mL to 1.2 ng/mL. The present method developed by our doping control laboratory was validated according to WADA technical documents for selectivity, limit of detection (LOD), carryover, reliability of detection, stability and recovery. The results show that the method has adequate recoveries and sensitivity, hence, it can be employed for routine screening in anti-doping laboratories.
Diagnostic Value of Synovial Fluid Biomarkers for Periprosthetic Joint Infection: A Prospective, Double-blind Trial.
Med Sci Monit
Ying Xu, Xueting Ma, Haoran Guo +4 more
BACKGROUND This prospective, double-blind study investigated the clinical diagnostic value of synovial fluid S100 calcium-binding protein A8 (S100A8) and S100 calcium-binding protein A9 (S100A9) in periprosthetic joint infection (PJI) and investigated the subtypes of a-defensin that have diagnostic value for PJI. MATERIAL AND METHODS Synovial fluid samples were collected from 82 patients with suspected PJI after total joint arthroplasty. Patients were divided into a PJI group (n=39) and non-PJI group (n=43). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used to determine S100A8, S100A9, alpha-defensin, and internal reference standards in synovial fluid. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficiency of S100A8, S100A9, and alpha-defensin for PJI, as well as the diagnostic value in combination with common biomarkers of infection. RESULTS S100A8, 3 variants of S100A9, and 3 alpha-defensins (human neutrophil peptides [HNP]1-3) in synovial fluid were significantly higher in the PJI group than in the non-PJI group (P<0.001). The sensitivity, specificity, and the area under ROC curve (AUC) for diagnosing PJI were 97.4%, 86.0%, and 0.964 (95% CI: 0.929-0.998), respectively, for synovial fluid S100A8; 87.2%, 88.4% and 0.902 (95% CI: 0.823-0.980), respectively, for S100A9; and 89.7%, 83.7%, and 0.933 (95% CI: 0.884-0.982), respectively, for HNP1-3. The diagnostic efficiency was improved when combined with synovial fluid white blood cell count and percentage of polymorphonuclear neutrophils. CONCLUSIONS Synovial fluid S100A8, S100A9, and HNP1-3 have satisfactory diagnostic efficiency for the diagnosis of PJI, which will help clinicians to accurately diagnose PJI.
Regulation of dermal fibroblasts by human neutrophil peptides.
Sci Rep
Nattarika Niwetbowornchai, Thanawat Chaisirirat, Sira Sriswasdi +6 more
Human neutrophil peptides (HNPs) can induce cell proliferation and activation so their growth promoting activities may have potential clinical benefit. This study investigated the effects of HNPs on human dermal fibroblasts. Differential gene expression in HNP-treated cells and genes involved in regulating intracellular pathways were explored. Dermal fibroblasts were isolated from healthy neonatal foreskin and treated with HNPs in 2D and 3D cell culture systems. The expression of cell proliferation (Ki-67) gene and cell activation (COL1A1) gene plus their proteins was measured. Differential gene expression was determined using RNA-seq, and upregulated and downregulated genes were mapped onto intracellular pathways by KEGG analysis and Gene Ontology databases. HNPs significantly increased cell proliferation without cytotoxicity whilst HNP1 enhanced expression of COL1A1 and type I collagen production in 2D cells and 3D spheroids. RNA-sequencing analysis showed gene clustering with clear separation between HNP1-treated and control groups. A heatmap of top 50 differentially expressed genes was consistent among HNP1-treated samples. Most upregulated genes were associated with cell proliferation and activation as mapped into intracellular pathways whilst most downregulated genes belonged to steroid/arachidonic acid metabolism and inflammatory signaling pathways. HNP1 increased cell proliferation and activation but reduced lipid metabolism and inflammation.
[Multidrug resistant narcolepsy].
Rev Neurol
A M González-García, M Morán-Sánchez, A R Sánchez-Serrano +3 more
Narcolepsy type 1 is a focal degenerative disease of the hypothalamus that selectively affects orexin (hypocretin)-producing neurons. It presents multiple clinical manifestations, both in wakefulness and in sleep. The symptoms are often so disruptive that they cause enormous suffering and impair patients' quality of life. Although a non-pharmacological approach is sometimes sufficient, the vast majority of patients need medication for adequate clinical management.
An injectable mitochondria-targeted nanodrug loaded-hydrogel for restoring mitochondrial function and hierarchically attenuating oxidative stress to reduce myocardial ischemia-reperfusion injury.
Biomaterials
Xiaoping Zhang, Yage Sun, Rong Yang +4 more
Timely reperfusion is the common treatment for myocardial infarction. However, ischemia-reperfusion (I/R) therapy can lead to oxidative stress and mitochondrial dysfunction that further aggravate myocardial injury, and no effective therapy is currently available for alleviating myocardial I/R injury. Herein, we engineer a mitochondria-targeted Szeto-Schiller (SS31) peptide modified-amphiphilic polymer (PTPS) that self-assembles into nanomicelles (PTPSCs) for loading cyclosporine A (CsA). The PTPSCs are then encapsulated into a pH/ROS dual responsive injectable hydrogel crosslinked with reversible imine and boronic ester bonds. The loaded PTPSCs are controllably delivered from the hydrogel matrix in response to the low pH and high ROS microenvironment of the I/R heart, thus realizing reconstruction of mitochondrial function and unprecedented hierarchical attenuation of oxidative stress. The boronic ester in the hydrogel consumes the ROS in cardiac microenvironment, and the mitochondria-targeted delivery of CsA is revealed to inhibit mitochondria-mediated apoptosis signaling pathway to prevent cardiomyocyte apoptosis, meanwhile attenuating the mitochondrial ROS output to reduce the level of cytosolic ROS. Additionally, SS31 can also serve as an antioxidant to consume ROS in the mitochondria. In rat model of myocardial I/R injury with administration of this injectable hydrogel, the targeted release of PTPSCs efficiently restores mitochondrial and cardiac function.
The Protective Effects of Water-Soluble Alginic Acid on the N-Terminal of Thymopentin.
Molecules
Haiyu Ji, Yuting Fan, Xiaoji Gao +5 more
Thymopentin (TP5) has exhibited strong antitumor and immunomodulatory effects in vivo. However, the polypeptide is rapidly degraded by protease and aminopeptidase within a minute at the N-terminal of TP5, resulting in severe limitations for further practical applications. In this study, the protective effects of water-soluble alginic acid (WSAA) on the N-terminal of TP5 were investigated by establishing an H22 tumor-bearing mice model and determining thymus, spleen, and liver indices, immune cells activities, TNF-α, IFN-γ, IL-2, and IL-4 levels, and cell cycle distributions. The results demonstrated that WSAA+TP5 groups exhibited the obvious advantages of the individual treatments and showed superior antitumor effects on H22 tumor-bearing mice by effectively protecting the immune organs, activating CD4+ T cells and CD19+ B cells, and promoting immune-related cytokines secretions, finally resulting in the high apoptotic rates of H22 cells through arresting them in S phase. These data suggest that WSAA could effectively protect the N-terminal of TP5, thereby improving its antitumor and immunoregulatory activities, which indicates that WSAA has the potential to be applied in patients bearing cancer or immune deficiency diseases as a novel immunologic adjuvant.
NAP (Davunetide): The Neuroprotective ADNP Drug Candidate Penetrates Cell Nuclei Explaining Pleiotropic Mechanisms.
Cells
Maram Ganaiem, Nina D Gildor, Shula Shazman +3 more
(1) Background: Recently, we showed aberrant nuclear/cytoplasmic boundaries/activity-dependent neuroprotective protein (ADNP) distribution in ADNP-mutated cells. This malformation was corrected upon neuronal differentiation by the ADNP-derived fragment drug candidate NAP (davunetide). Here, we investigated the mechanism of NAP nuclear protection. (2) Methods: CRISPR/Cas9 DNA-editing established N1E-115 neuroblastoma cell lines that express two different green fluorescent proteins (GFPs)-labeled mutated ADNP variants (p.Tyr718* and p.Ser403*). Cells were exposed to NAP conjugated to Cy5, followed by live imaging. Cells were further characterized using quantitative morphology/immunocytochemistry/RNA and protein quantifications. (3) Results: NAP rapidly distributed in the cytoplasm and was also seen in the nucleus. Furthermore, reduced microtubule content was observed in the ADNP-mutated cell lines. In parallel, disrupting microtubules by zinc or nocodazole intoxication mimicked ADNP mutation phenotypes and resulted in aberrant nuclear-cytoplasmic boundaries, which were rapidly corrected by NAP treatment. No NAP effects were noted on ADNP levels. Ketamine, used as a control, was ineffective, but both NAP and ketamine exhibited direct interactions with ADNP, as observed via in silico docking. (4) Conclusions: Through a microtubule-linked mechanism, NAP rapidly localized to the cytoplasmic and nuclear compartments, ameliorating mutated ADNP-related deficiencies. These novel findings explain previously published gene expression results and broaden NAP (davunetide) utilization in research and clinical development.
Nanowired delivery of antibodies to tau and neuronal nitric oxide synthase together with cerebrolysin attenuates traumatic brain injury induced exacerbation of brain pathology in Parkinson's disease.
Int Rev Neurobiol
Asya Ozkizilcik, Aruna Sharma, Lianyuan Feng +7 more
Concussive head injury (CHI) is one of the major risk factors for developing Parkinson's disease in later life of military personnel affecting lifetime functional and cognitive disturbances. Till date no suitable therapies are available to attenuate CHI or PD induced brain pathology. Thus, further exploration of novel therapeutic agents are highly warranted using nanomedicine in enhancing the quality of life of veterans or service members of US military. Since PD or CHI induces oxidative stress and perturbs neurotrophic factors regulation associated with phosphorylated tau (p-tau) deposition, a possibility exists that nanodelivery of agents that could enhance neurotrophic factors balance and attenuate oxidative stress could be neuroprotective in nature. In this review, nanowired delivery of cerebrolysin-a balanced composition of several neurotrophic factors and active peptide fragments together with monoclonal antibodies to neuronal nitric oxide synthase (nNOS) with p-tau antibodies was examined in PD following CHI in model experiments. Our results suggest that combined administration of nanowired antibodies to nNOS and p-tau together with cerebrolysin significantly attenuated CHI induced exacerbation of PD brain pathology. This combined treatment also has beneficial effects in CHI or PD alone, not reported earlier.
Thymosin beta-4 participate in antibacterial immunity and wound healing in black tiger shrimp, Penaeus monodon.
Fish Shellfish Immunol
Changhong Lin, Lihua Qiu, Pengfei Wang +3 more
Thymosin beta-4 (Tβ4) is a ubiquitous protein with multiple and diverse intracellular and extracellular functions in vertebrates, which play fundamental roles in innate immune against pathogens and wound healing. In this study, the full-length cDNA of Tβ4 was cloned from Penaeus monodon (designated as PmTβ4), using the technology of rapid amplification of cDNA ends (RACE). The cDNA of PmTβ4 was 1361 bp with an open reading frame (ORF) of 501 bp, which encoding a polypeptide of 166 amino acid. The Quantitative Real-time PCR (qRT-PCR) analysis results showed that PmTβ4 was ubiquitously expressed in all the tested shrimp tissues, with the highest expression level was detected in the hemolymph, while the lowest expression level in the muscle. The expression level of PmTβ4 was significantly up-regulated in hepatopancreas after challenged by Vibrio parahaemolyticus, Vibrio harveyi and Staphylococcus aureus. In vitro antimicrobial test showed that the recombinant protein of PmTβ4 (rPmTβ4) had broad-spectrum of antimicrobial activity, which could inhibit both the growth of gram-negative bacteria and gram-positive bacteria, including Vibrio vulnificus, V. parahaemolyticus, Streptococcus agalactiae, S. aureus and Aeromonas hydrophila. Moreover, rPmTβ4 had a certain binding ability to different bacteria, and this binding ability exhibits a strong dose-dependent effect. In vivo, PmTβ4 could facilitate external bacterial clearance in shrimp, and have beneficial to shrimp survival post V. parahaemolyticus infection. Furthermore, wound-healing assay was carried out to study the role of PmTβ4 in the process of wound healing. The results showed that the PmTβ4 expression was significantly up-regulated by injury treatment, and exerted positive effects to promote wound healing. In addition, PmTβ4 can significantly increase the expression level of superoxide dismutase (SOD) and Catalase (CAT) after injury treatment in shrimp, which would involve in scavenging reactive oxygen species (ROS) caused by the wound. In conclusion, these results indicated that PmTβ4 may play important roles in antibacterial immunity and wound healing in Penaeus monodon.
Oral supplementation with fish cartilage hydrolysate in an adult population suffering from knee pain and function discomfort: results from an innovative approach combining an exploratory clinical study and an ex vivo clinical investigation.
BMC Musculoskelet Disord
Henrotin Yves, Julie Herman, Melanie Uebelhoer +10 more
Aging is frequently associated with impairments of the musculoskeletal system and many elderly people experience joint discomfort or pain which might reduce their ability to move and consequently alter their quality of life. A beneficial effect of fish cartilage hydrolysate (FCH) on pain and joint function has recently been shown in an ACLT/pMMx osteoarthritis rat model.
Endogenous opiates and behavior: 2022.
Peptides
Richard J Bodnar
This paper is the forty-fifth consecutive installment of the annual anthological review of research concerning the endogenous opioid system, summarizing articles published during 2022 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides and receptors as well as effects of opioid/opiate agonists and antagonists. The review is subdivided into the following specific topics: molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors (1), the roles of these opioid peptides and receptors in pain and analgesia in animals (2) and humans (3), opioid-sensitive and opioid-insensitive effects of nonopioid analgesics (4), opioid peptide and receptor involvement in tolerance and dependence (5), stress and social status (6), learning and memory (7), eating and drinking (8), drug abuse and alcohol (9), sexual activity and hormones, pregnancy, development and endocrinology (10), mental illness and mood (11), seizures and neurologic disorders (12), electrical-related activity and neurophysiology (13), general activity and locomotion (14), gastrointestinal, renal and hepatic functions (15), cardiovascular responses (16), respiration and thermoregulation (17), and immunological responses (18).