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Effect of SARS-CoV-2 Infection on Selected Parameters of the Apelinergic System in Repeat Blood Donors.
Biomedicines
Marta Stanek, Anna Leśków, Dorota Diakowska
Background: SARS-CoV-2 enters cells primarily by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, thereby blocking its physiological functions, affecting the apelinergic system, and inhibiting the cleavage of its peptides. The appropriate concentration of peptides in the apelinergic system influences the maintenance of homeostasis and protects against cardiovascular diseases. In our research, we determined the level of selected parameters of the apelinergic system-apelin (AP), elabela (ELA), and the apelin receptor (APJ)-in repeat blood donors. Methods: We analyzed 120 serum samples obtained from 30 repeat donors (study group) within four time periods after a SARS-CoV-2 infection: <60 days, 61-90 days, 91-120 days, and >120 days. We compared the results from the study groups with those of the control group, which consisted of 30 serum samples collected from donors donating blood in the years 2018-2019. Results: We observed that the AP, ELA, and APJ concentrations in the control group are higher than in any period in the study group. In the study group, the concentrations of AP and ELA increased in subsequent study periods. AP and ELA concentrations were lower shortly after SARS-CoV-2 transfection and then slowly increased in subsequent periods. APJ concentrations, on the other hand, were lowest at 61-90 days after the infection, but the decrease, relative to their level in healthy subjects, was significant in every period studied. Conclusions: The results suggest that infection with SARS-CoV-2 causes changes in the parameters of the apelinergic system, both after a short period of time has passed since the onset of the SARS-CoV-2 infection, and even up to 4 months after the infection.
Cannabidiol, a Strategy in Aging to Improve Redox State and Immunity in Male Rats.
Int J Mol Sci
Mónica De la Fuente, Noelia Joyera, Judith Félix +4 more
Aging is characterized by oxidative stress and immune function impairment, and is associated with increased morbidity. Cannabidiol (CBD) has anti-oxidant properties, but its role in aging has been scarcely studied. This work aims to test the effect of CBD on the redox state and immunity during aging in rats. In this study, 15-month-old male Long Evans rats received 10 mg/kg b.w/day of CBD in their diet for 10 weeks and were compared with same-age control and 2-month-old rats serving as a young control group, both following a standard diet. After treatment, they were sacrificed, and the spleen, thymus, and total blood cells were collected. Redox parameters such as glutathione reductase and peroxidase activities, reduced (GSH) and oxidized (GSSG) glutathione concentration, GSSG/GSH ratio, and lipid peroxidation were evaluated. Moreover, immune functions (chemotaxis, natural killer activity, and lymphoproliferation) were analyzed in the spleen. Results show that the 15-month-old control rats exhibited increased oxidative stress and immunosenescence compared to the 2-month-old rats. However, the CBD-treated animals showed higher anti-oxidant defenses, lower oxidants in the spleen, thymus, and blood cells, and better immunity in the spleen than the corresponding age-matched controls. Therefore, CBD administration neutralizes oxidative stress and improves immunity, suggesting it is a strategy for achieving healthy aging.
Does Incretin Agonism Have Sustainable Efficacy?
Cells
Sok-Ja Janket, Miyo K Chatanaka, Dorsa Sohaei +3 more
Recent clinical trials using synthetic incretin hormones, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists have demonstrated that these treatments ameliorated many complications related to obesity, emphasizing the significant impact of body weight on overall health. Incretins are enteroendocrine hormones secreted by gut endothelial cells triggered by nutrient ingestion. The phenomenon that oral ingestion of glucose elicits a much higher insulin secretion than intra-venous injection of equimolar glucose is known as the incretin effect. This also alludes to the thesis that food intake is the root cause of insulin resistance. Synthetic GLP-1 and GIP agonists have demonstrated unprecedented glucoregulation and body weight reduction. Also, randomized trials have shown their ability to prevent complications of obesity, including development of diabetes from prediabetes, reducing cardiovascular disease risks and renal complications in diabetic patients. Moreover, the benefits of these agonists persist among the patients who are already on metformin or insulin. The ultimate question is "Are these benefits of incretin agonism sustainable?" Chronic agonism of pancreatic β-cells may decrease the number of receptors and cause β-cell exhaustion, leading to β-cell failure. Unfortunately, the long-term effects of these drugs are unknown at the present because the longest duration in randomized trials is 3 years. Additionally, manipulation of the neurohormonal axis to control satiety and food intake may hinder the long-term sustainability of these treatments. In this review, we will discuss the incretins' mechanism of action, challenges, and future directions. We will briefly review other molecules involved in glucose homeostasis such as amylin and glucagon. Amylin is co-expressed with insulin from the pancreas β-cells but does not have insulinotropic function. Amylin suppresses glucagon secretion, slowing gastric emptying and suppressing the reward center in the central nervous system, leading to weight loss. However, amylin can self-aggregate and cause serious cytotoxicity and may cause β-cell apoptosis. Glucagon is secreted by pancreatic α-cells and participates in glucose homeostasis in a glucose-dependent manner. In hypoglycemia, glucagon increases the blood glucose level by glycogenolysis and gluconeogenesis and inhibits glycogenesis in the liver. Several triple agonists, in combination with dual incretins and glucagon, are being developed.
Nebulized vasopressin penetrates CSF and improves social cognition without inducing aggression in a rhesus monkey model of autism.
Proc Natl Acad Sci U S A
Catherine F Talbot, Ozge Oztan, Sierra M V Simmons +7 more
Low cerebrospinal (CSF) arginine vasopressin (AVP) concentration is a biomarker of social impairment in low-social monkeys and children with autism, suggesting that AVP administration may improve primate social functioning. However, AVP administration also increases aggression, at least in "neurotypical" animals with intact AVP signaling. Here, we tested the effects of a voluntary drug administration method in low-social male rhesus monkeys with high autistic-like trait burden. Monkeys received nebulized AVP or placebo, using a within-subjects design. Study 1 (N = 8) investigated the effects of AVP administration on social cognition in two tests comparing responses to social versus nonsocial stimuli. Test 1: Placebo-administered monkeys lacked face recognition memory, whereas face recognition memory was "rescued" following AVP administration. In contrast, object recognition memory was intact and did not differ between administration conditions. Test 2: Placebo-administered monkeys did not respond to conspecific social communication cues, whereas following AVP administration, they reciprocated affiliative communication cues with species-typical affiliative responses. Importantly, AVP administration did not increase aggressive responses to conspecific aggressive or affiliative overtures. Study 2 (N = 4) evaluated the pharmacokinetics of this administration method. Following AVP nebulization, we observed a linear increase in cisternal CSF AVP levels, and a quadratic rise and fall in blood AVP levels. These findings indicate that nebulized AVP likely penetrates the central nervous system, selectively promotes species-typical responses to social information, and does not induce aggression in low-social individuals. Nebulized AVP therefore may hold promise for managing similar social symptoms in people with autism, particularly in very young or lower functioning individuals.
Cerebrolysin Induces Motor Recovery Along with Plastic Changes in Motoneurons and an Increase in GAP43 Protein in the Ventral Spinal Cord Following a Kainic Acid Excitotoxic Lesion in the Rat Motor Cortex.
Neurochem Res
Nestor I Martínez-Torres, Jhonathan Cárdenas-Bedoya, Blanca Miriam Torres-Mendoza
Lesions in the motor cortex induced by contusions or pathological insults can exert the degeneration of afferent neurons lying distal to these lesions. Axon degeneration and demyelination are hallmarks of several diseases sharing pathophysiological and clinical characteristics. These conditions are very disabling due to the disruption of motor abilities, with lesions that affect this area proving to be a therapeutic challenge, which has driven increasing efforts to search for treatments. Cerebrolysin (CBL) contains a mix of pig brain-derived peptides with activity similar to neurotrophic factors. Here, the effect of cerebrolysin administration on the motor impairment produced by kainic acid (KA) lesion of the motor cortex was evaluated in Sprague-Dawley female rats (n = 27), defining its effect on motoneurons dendritic tree changes, dendritic spine density and GAP43 presence in the ventral thoracolumbar regions of the spinal cord. Ten days after the KA lesion of the motor cortex, rats were administered cerebrolysin, and their motor performance was evaluated using the "Basso, Beattie, and Bresnahan" (BBB) and Bederson scores. Cerebrolysin administration improved motor activity according to the BBB and Bederson scales, along with increased dendritic intersections and dendritic spine density on motoneurons. There was also a significant increase in GAP43 protein, suggesting that CBL may promote plastic changes through this protein, among others. Hence, this study proposes that cerebrolysin could promote motor recovery following motor cortex lesions by driving neuronal changes and dendritic spine plasticity on motoneurons and an increase in GAP43 protein, along with other mechanisms.
Targeting CD36 With EP 80317 Reduces Remote Inflammatory Response to Hind Limb Ischemia-Reperfusion in Mice.
J Biochem Mol Toxicol
Hanan Elimam, Jade Gauvin, David N Huynh +7 more
Reperfusion of ischemic skeletal muscle triggers oxidative stress and an immediate inflammatory reaction, leading to damage of distant organs such as the lungs. The inflammatory process implicates numerous mediators, including cytokines, chemokines, and arachidonic acid metabolites. In the orchestration of the inflammatory cascade, a critical role is played by the cluster of differentiation-36 receptor (CD36), a scavenger receptor class B protein (SR-B2) which is expressed on macrophages and functions as a Toll-like receptor coreceptor. A mouse model of hind limb ischemia-reperfusion has been used to investigate the interplay between CD36 signaling and remote inflammation: leukocyte recruitment, regulation of the nucleotide-binding domain leucin-rich repeat and pyrin-containing receptor 3 (NLRP3) inflammasome, and release of nuclear factor-kappa B (NF-ĸB) and arachidonic acid metabolites. Levels of reactive oxygen species, inflammatory mediators, and gene expression were measured in blood and lung tissue samples collected from anesthetized mice on which unilateral hind limb ischemia was induced by rubber band constriction for 30 min followed by reperfusion for 3 h. The CD36 modulator EP 80317, a member of the growth hormone releasing peptide 6 family, was employed as a pharmacological agent to mitigate distant lung injury following skeletal limb ischemia-reperfusion. Targeting CD36 on monocytes/macrophages, EP 80317 abated pro-inflammatory signaling and transcriptional activity encompassing lipid and cytokine mediators. Targeting CD36 was shown to offer promise for curtailing tissue injury following hind limb ischemia-reperfusion.
Probing for peptidic drugs (2-10 kDa) in doping control blood samples.
Anal Sci Adv
Andreas Thomas, Sam Thilmany, Amelie Hofmann +1 more
Bioactive peptides with a molecular mass between 2 and 10 kDa represent an important class of substances banned in elite sports, which has been recognized with an increasing number and variety of substances by anti-doping organizations. Also, the annually renewed list of prohibited substances of the World Anti-Doping Agency (WADA) explicitly mentions more and more of these peptides, and efficient testing procedures are required. Even under simplified sample preparation conditions, liquid chromatography coupled to high-resolution mass spectrometry (with resolution properties > 100,000 full width at half maximum) offers suitable conditions for this task and can therefore be used as an initial testing procedure. In contrast to urine, blood analysis essentially relies on the detection of intact peptide hormones, and the expected concentrations are commonly higher in blood samples than in urine. This facilitates the analysis, and a generic sample preparation by means of mixed-mode solid-phase extraction could be realized in this study. Co-extraction and analysis of several different peptides such as insulins (human, lispro, aspart, glulisine, tresiba, detemir, glargine, bovine insulin and porcine insulin), growth hormone releasing hormones (sermorelin, CJC-1295 and tesamorelin), insulin-like growth factors (long-R3-IGF-I, R3-IGF-I and Des1-3-IGF-I) and mechano growth factors (human MGF and MGF-Goldspink) with criteria that fulfil the requirements of the WADA documents (TD2022 MRPL) for doping controls. The proof of principle was shown by the analysis of post administration samples after treatment with synthetic insulin analogues.
Proteomic analysis of the human amniotic mesenchymal stromal cell secretome by integrated approaches via filter-aided sample preparation.
J Proteomics
Alexandra Muntiu, Andrea Papait, Federica Vincenzoni +6 more
The immunomodulatory, anti-inflammatory and regenerative properties of the human amniotic mesenchymal stromal cells (hAMSCs) secretome are acknowledged but the understanding of the specific bioactive components remains incomplete. To address these limitations, the present investigation aimed to profile the proteins and peptides content of the hAMSC secretome through sample pretreatment and fractionation on 10 kDa molecular cut-off FASP (Filter Aided Sample Preparation) device and LC-MS analysis. The filter retained protein fraction underwent trypsin digestion, while the unretained was collected unchanged for intact small proteins and peptides analysis. This combined approach (C-FASP) collects in a single step two complementary fractions, advantageously saving sample volume and time of analysis. The bottom-up analysis of the C-FASP proteins fraction >10 kDa confirmed our previous findings, establishing a set of proteins consistently characterizing the hAMSC secretome. The analysis of the fraction <10 kDa, never been investigated to our knowledge, identified peptide fragments of thymosin beta 4 and beta 10, collagen alpha 1 chains I and III, alpha-enolase, and glyceraldehyde-3-phosphate dehydrogenase, involved in wound healing, anti-inflammatory response, tissue repair and regeneration, key biological activities of the secretome. C-FASP provided a comprehensive molecular profile of the hAMSC secretome offering new insights for enhanced therapeutic applications in regenerative medicine. SIGNIFICANCE: In this investigation we originally present the comprehensive proteomic investigation of the human amniotic mesenchymal stromal cell secretome by combining the analysis of the proteome and of the peptidome following sample pretreatment and fractionation by Filter Aided Sample Preparation (FASP) with 10 kDa molecular cut-off in coupling with LC-MS analysis. The proteome fraction retained by FASP filter was analyzed after enzymatic digestion, while the unretained fraction, below 10 kDa molecular mass, was analyzed unchanged in its intact form. This dual approach provides novel insights, previously unexplored, into the molecular components potentially responsible for the immunomodulatory and anti-inflammatory properties of the hAMSC secretome. These findings could significantly enhance the therapeutic potential of hAMSCs in regenerative medicine.
Humulus lupulus L.: Evaluation of Phytochemical Profile and Activation of Bitter Taste Receptors to Regulate Appetite and Satiety in Intestinal Secretin Tumor Cell Line (STC-1 Cells).
Mol Nutr Food Res
Ludovica Lela, Vittorio Carlucci, Chrissa Kioussi +4 more
Inflorescences of the female hop plant (Humulus lupulus L.) contain biologically active compounds, most of which have a bitter taste. Given the rising global obesity rates, there is much increasing interest in bitter taste receptors (TAS2Rs). Intestinal TAS2Rs can have beneficial effects on obesity when activated by bitter agonists. This study aims to investigate the mechanism of action of a hydroalcoholic hop extract in promoting hormone secretion that reduces the sense of hunger at the intestinal level through the interaction with TAS2Rs.
The mechanism of transcutaneous gastric pacing treatment on gastrointestinal motility recovery and inflammation improvement in early-stage acute pancreatitis patients.
BMC Gastroenterol
Zhenyu Jia, Lingchao Kong, Xiaochun Lu +4 more
Acute pancreatitis (AP) is often accompanied by gastrointestinal motility disorders. The purpose of this study was to investigate the efficacy and possible mechanism of transcutaneous gastric pacing (TGP) in early-stage AP patients.
Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress.
Eur J Pharmacol
Ludmila S Inozemtseva, Ksenia A Yatsenko, Natalya Yu Glazova +5 more
Current antidepressant therapy shows substantial limitations, and there is an urgent need for the development of new treatment strategies for depression. Stressful events and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis play an important role in the pathogenesis of depression. HPA axis activity is self-regulated by negative feedback at several levels including adrenocorticotropic hormone (ACTH)-mediated feedback. Here, we investigated whether noncorticotropic synthetic analogs of the ACTH(4-10) fragment, ACTH(4-7)-Pro-Gly-Pro (Semax) and Ac-Nle4-cyclo[Asp5-His6-D-Phe7-Arg8-Trp9-Lys10]ACTH(4-10)-NH2 (Melanotan II (MTII), a potent agonist of melanocortin receptors), have potential antidepressant activity in a chronic unpredictable stress (CUS) rat model of depression. Stressed and control male adult Sprague-Dawley rats received daily intraperitoneal injections of saline or a low dose (60 nmol/kg of body weight (BW)) of Semax or MTII. Rats were monitored for BW and hedonic status, as measured in the sucrose preference test. We found that chronic treatment with Semax and MTII reversed or substantially attenuated CUS-induced anhedonia, BW gain suppression, adrenal hypertrophy and a decrease in the hippocampal levels of BDNF. In the forced swim test, no effects of the CUS procedure or peptides on the duration of rat immobility were detected. Our findings show that in the CUS paradigm, systemically administered ACTH(4-10) analogs Semax and MTII exert antidepressant-like effects on anhedonia and hippocampal BDNF levels, and attenuate markers of chronic stress load, at least in male rats. The results support the argument that ACTH(4-10) analogs and other noncorticotropic melanocortins may have promising therapeutic potential for the treatment and prevention of depression and other stress-related pathologies.
Impact of Collagen Peptide Supplementation in Combination with Long-Term Physical Training on Strength, Musculotendinous Remodeling, Functional Recovery, and Body Composition in Healthy Adults: A Systematic Review with Meta-analysis.
Sports Med
Kevin Bischof, Anna Maria Moitzi, Savvas Stafilidis +1 more
Over the past decade, collagen peptide (CP) supplements have received considerable attention in sports nutrition research. These supplements have shown promising results in improving personal health, enhancing athletic performance, and preventing injuries in some but not all studies.
Microplastic and the Enteric Nervous System: Effect of PET Microparticles on Selected Neurotransmitters and Cytokines in the Porcine Ileum.
Int J Mol Sci
Ismena Gałęcka, Jarosław Całka
Microplastic is an environmental hazard to which both animals and humans are exposed. Current reports show that it can cause inflammation, including in the gastrointestinal tract. To examine the impact on the ileum, 15 eight-week-old gilts (five individuals/group) were exposed to PET microplastics (7.6 µm-416.9 µm) at a dose of 0.1 g/day or 1 g/day for 28 days. The collected ileum fragments were investigated for the cytokine concentrations (IL-1β, IL-6, IL-8, IL-10, and TNF-α; ELISA test), neuron populations (cocaine and amphetamine-regulated transcript, galanin, neuronal nitric oxide synthase, substance P, vesicular acetylcholine transporter, and vasoactive intestinal peptide; immunofluorescence staining), and morphometric parameters (histological analysis). Under the influence of MP-PET, there was a reduction in the populations of CART- and GAL-positive neurons in the submucosal plexuses and of nNOS-, VAChT-, and VIP-positive neurons in all the plexuses. In contrast, there was an increase in GAL-positive neurons in the myenteric plexus and SP-positive neurons in all the plexuses. The concentrations of IL-1β, IL-6, IL-8, IL-10, and TNF-α did not undergo statistically significant changes under the influence of the low or high dose of MP-PET. The changes in the histological structure exclusively concerned the thinning of the mucosa and the muscularis externa. The results support the thesis that MP-PET is not neutral to the ileal cells.
Giant Centella asiatica, a novel cultivar rich in madecassoside and asiaticoside, suppresses α‑melanocyte‑stimulating hormone‑induced melanogenesis through MC1R binding.
Int J Mol Med
Jiwon Seo, Chanhyeok Jeong, Seung Man Oh +9 more
The present study investigated the anti‑melanogenesis effects of Giant Centella asiatica (GCA), a new cultivator of Centella asiatica (CA) cataloged by the Korea Forest Service in 2022, and compared its efficacy with that of traditional CA. GCA has a high yield per unit area and enhanced antioxidant properties. The anti‑melanogenic effects of GCA were investigated using B16F10 melanoma cells and a 3D human skin‑equivalent model. Key molecular mechanisms were elucidated through western blotting, cAMP assays and molecular docking studies. Focus was addressed on the effect of GCA on skin whitening by comparing the ability of a GCA extract to inhibit melanin production in B16F10 melanoma cells and a 3D human skin‑equivalent model to that of CA. The results showed that the GCA extracts more effectively reduced melanin production, which was attributed to their higher content of two active components, madecassoside and asiaticoside. Further investigation revealed that GCA primarily inhibited melanogenesis through the PKA‑cAMP response element‑binding (CREB)‑microphthalmia‑associated transcription factor (MITF) axis, a key regulatory pathway in melanin synthesis. Notably, the present study, to the best of our knowledge, is the first to demonstrate that madecassoside and asiaticoside, the two principal compounds in GCA, directly bound to MC1R, which contributed to the significant skin‑whitening effects. Moreover, GCA reduced melanin production in a 3D human skin‑equivalent model, showing efficacy within a complex skin environment. These results demonstrated the superior effectiveness of GCA to that of CA for skin anti‑melanogenesis, indicating its potential as a promising natural material for targeting pigmentation disorders.
Dynamic Hydration and Viscosity Control of Konjac Glucomannan Enhance Long-Term Antiobesity Effects by Reducing Food Intake in High-Fat-Diet-Fed Mice.
J Agric Food Chem
Liping Guo, Wallace Yokoyama, Ling Chen +2 more
The purpose of this study was to investigate the necessity and importance of dynamic hydration rate and ultimate viscosity control of konjac glucomannan (KGM) for long-term antiobesity effects in C57BL/6J mice on high-fat (HF) diets. KGM supplementation effectively attenuated HF-diet-induced increases in body and tissue weights. The hydration rate and viscosity changes of KGM in the digestive tract were found to have marked impacts on antiobesity effects. KGM with medium hydration and viscosity slowed gastric emptying and intestinal transit, leading to prolonged presence in the lower ileum, increased satiety-related hormones (GLP-1 and PYY), and an 18.27% reduction in daily food intake over 10 weeks (p < 0.05). This resulted in the greatest reduction in weight gain among HF-fed mice. In contrast, KGM with faster hydration and higher viscosity provided only short-term satiety due to rapid dilution. Furthermore, KGM improved metabolic health and altered glycolipid metabolism gene transcription while enriching beneficial gut bacteria; however, no significant differences were observed among the KGM groups in these effects. These findings highlight that synchronizing KGM's hydration rate and viscosity with digestive processes is crucial for regulating satiety and achieving long-term weight loss.
Physicochemical and structural analysis of N-phenylacetyl-L-prolylglycine ethyl ester (Noopept) - An active pharmaceutical ingredient with nootropic activity.
J Pharm Biomed Anal
Szymon Kamil Araj, Łukasz Szeleszczuk, Tomasz Gubica +5 more
N-Phenylacetyl-L-prolylglycine ethyl ester (Noopept, GVS-111, omberacetam) is an orally available active pharmaceutical ingredient (API), with neuroprotective properties and ability to enhance cognitive function. It belongs to nootropic family of drugs and is included in the group of racetams, although its chemical structure is quite different than the other compounds from this group, including the most popular one - piracetam. The mechanism of action of this API is multifaced and is considered to be involving modulation of various neurotransmitter systems within the brain. Despite the significant amount of works devoted to the pharmacodynamics of Noopept, very little is known about its structural and physicochemical properties. Therefore, the aim of current study was to investigate this API in a very thorough way. In this work, the detailed physicochemical analysis of Noopept has been done using TGA/DSC, 1H and 13C liquid state NMR, 13C CP/MAS NMR, SEM, SCXRD, and PXRD. Additionally, quantum chemical DFT computations under periodic boundary conditions, using CASTEP, were conducted to facilitate the analysis of experimental results. Besides, we've performed a polymorphism screening of this molecule.
Plasma Protein Biomarkers and Long-Term Cardiovascular Mortality Risk in Patients With Chronic Coronary Heart Disease.
J Am Heart Assoc
Ralph A H Stewart, Kristy P Robledo, Andrew M Tonkin +9 more
Protein biomarkers that reflect different pathophysiological pathways have been associated with the risk of adverse cardiovascular events. However, it is uncertain whether these associations are sustained with increasing years after the biomarkers are measured.
Barbie drug identification: Not a child's play.
J Forensic Sci
Marine Deville, Corinne Charlier
Various samples-including two vials with a pharmaceutical appearance-were submitted to the laboratory for identification. The aim of this work was to describe the unique characteristics observed during the analysis of the powder contained in the vial. Samples were submitted to HPLC-DAD, UHPLC-TOF-MS, and/or UPLC-MS-MS analysis. The majority of the samples were easily identified as standard drugs of abuse. The main difficulty lay in identifying the powder in the vials. No match was found in the library through HPLC-DAD analysis. Fortunately, the vials were labeled as "Melanotan II", although the UV spectrum was not available. Mass spectrometric analysis of melanotan II was challenging, as it is a small peptide with a molecular weight of 1024 Da, which is significantly heavier than classical drugs that the laboratory usually handles. As a result, mass spectrometer's parameters can be limited to detect masses up to 1000 Da. Additionally, melanotan II is multi-charged which is also unusual for compounds typically targeted in our daily work. Finally, the reference standard allowed us to confirm the identification with both instruments, and determine the purity of 30%. Melanotan II is not approved on the market due to safety concerns. It is used illegally mainly for tanning, explaining its nickname "Barbie drug". To conclude, analysis of melanotan II was challenging as it is heavy and doubly charged. Moreover, its UV spectrum was initially not available in the literature. The difficulties faced by forensic scientists in detecting this drug may explain its popularity on the illicit market.
A Prospective and Randomized Control Study on Effects of Thymalfasin for Injection on Perioperative Immune Function and Long-term Prognosis of Patients with Colorectal Cancer.
Biotechnol Genet Eng Rev
Wenbo Niu, Zhiying Li, Zhihan Li +5 more
The objective of this study is to explore the effects of thymalfasin for injection on perioperative immune function and long-term prognosis of patients with colorectal cancer (CRC). In total, 400 patients who entered the groups from February 2019 to January 2021 and underwent radical resection of CRC in the Fourth Hospital of Hebei Medical University were the study subjects. They were separated into experimental group (0-199, XELOX chemotherapy and thymalfasin for injection) and control group (200-400, XELOX chemotherapy) by random number table, and the experimental group was randomly divided into conventional-dose group (n = 100, 1.6 mg of thymalfasin for injection, twice a week) and high-dose group (n = 100, 1.6 mg of thymalfasin for injection, thrice a week) according to a ratio of 1:1, to analyze the effects of different treatment schemes on perioperative immune function and long-term prognosis of CRC patients. Compared with control group, the conventional-dose group and high-dose group had notably lower incidences of perioperative infection (P < 0.05), with no significant difference in both groups (P > 0.05). The experimental group had significantly lower overall incidence of early and late postoperative complications, local recurrence rate and the incidence of distant metastasis, and higher perioperative immune function indexes and median disease free survival (DFS) (P < 0.05).         The conventional-dose and high-dose thymalfasin for injection effectively improves the perioperative immune function of CRC patients and reduces the incidence of postoperative complications, as an effective treatment for such patients, which can benefit patients.
Association of mid-regional pro-adrenomedullin with office and 24-h ambulatory blood pressure in a Swiss general population sample.
J Hypertens
Julia Baldwin, Michel Burnier, Belen Ponte +4 more
Adrenomedullin (ADM) is a potent vasodilator. The association between plasma ADM levels and blood pressure (BP) remains unclear. We assessed the association between mid-regional-pro-ADM (MR-proADM) and BP in a multicenter population- and family-based cohort.