In vitro evidence of oncofetal antigen and TLR-9 agonist co-delivery by alginate nanovaccines for liver cancer immunotherapy.

Liver cancer is the most common malignant tumor and liver cancer immunotherapy has been one of the research hotspots. To induce antigen-specific antitumor immune responses against liver cancer, we developed antigen and adjuvant co-delivery nanovaccines (APPCs). Polyanionic alginate (ALG) and polycationic polyethyleneimine (PEI) were utilized to co-deliver a glypican-3 peptide antigen and an unmethylated cytosine-phosphate-guanine (CpG) adjuvant by electrostatic interactions. A cellular uptake study confirmed that APPC could promote antigen and adjuvant uptake by dendritic cells (DCs). Importantly, APPC facilitated the endosomal escape of the peptide for antigen delivery into the cytoplasm. In addition, APPC showed significant stimulation of DC maturation in vitro. APPC could also efficiently prime DCs and induce cytotoxic T lymphocyte responses in vivo. The in vitro cell viability assay and the in vivo histocompatibility showed that APPC was non-toxic within the tested concentration. This study demonstrates that the peptide antigen and the CpG adjuvant co-delivery nanovaccine have potential applications in liver cancer immunotherapy.

Green tea peptides ameliorate diabetic nephropathy by inhibiting the TGF-ß/Smad signaling pathway in mice.

Diabetic nephropathy (DN) is the most important cause of middle and late-stage chronic kidney disease. Green tea polypeptides are extracted from tea pomace, and exhibit various pharmacological effects. In this study, we analyzed the reno-protective effects of green tea peptides in diabetic db/db mice, and explored the underlying mechanisms. Peptide treatment for 5 weeks significantly reduced the blood glucose levels and other indices of diabetes, and alleviated renal injury measured in terms of blood creatinine, urea nitrogen and urinary albumin/urinary creatinine levels. Mechanistically, the green tea peptides downregulated p-Smad2/3, α-SMA, ZO-1 and vimentin proteins in the kidney tissues, and elevated Smad7. Thus, green tea peptides inhibited the deposition of ECM proteins by suppressing excessive activation of the TGF-ß/Smad signaling pathway and reducing fibronectin levels. On the other hand, tea peptides ameliorated renal injury by inhibiting the production of inflammatory factors (iNOS and TNF-α) by suppressing the NF-κB signaling pathway. In addition, we confirmed the inhibitory effect of green tea peptides on the TGF-ß/Smad signaling pathway in TGF-ß1-stimulated HK-2 cells. Therefore, tea peptides can be considered as an effective candidate for alleviating DN.

Collagen Peptides, in Association with Vitamin C, Sodium Hyaluronate, Manganese and Copper, as Part of the Rehabilitation Project in the Treatment of Chronic Low Back Pain.

BACKGROUND AND OBJECTIVE: Low back pain (LBP) is a frequent symptom. Among the causes that can determine it, lumbar osteoarthritis plays an important role. Therapeutic exercise, according to McKenzie method, has been shown to be effective in the treatment of LBP. Oral supplementation with collagen peptides represents a new therapeutic possibility in osteoarthritis. The aim of this study is to evaluate the combined efficacy of therapeutic exercise and oral administered viscosupplements in the treatment of osteoarthritis-related chronic LBP. METHODS: Sixty patients were recruited and randomly divided into two groups (Group A and B). Group A performed only kinesitherapy, Group B carried out the same kinesitherapy combined with the daily administration of food supplements such as Fortigel®, Vitamin C, sodium hyaluronate, manganese and copper, during the whole treatment period. Patients were evaluated at the time of recruitment (T0), at the end of the treatment (T1 - 3 weeks after T0) and 6 weeks after T1 (T2). The outcome measures used were: Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), and Short Form-12 (SF-12). RESULTS: All the outcomes improved significantly at T1 in both groups, but more markedly in group B. Furthermore, in group A at T2, there was a statistically significant worsening in the scores of VAS, ODI and physical component of the SF-12, while in group B, this variation has not been detected. CONCLUSION: The combination of rehabilitation based on McKenzie back exercises and oral viscosupplementation with Fortigel®, Vitamin C, sodium hyaluronate, manganese and copper represents a valid option in patients with chronic LBP, as it ensures pain relief and improvement in the quality of life and in lumbar spine functionality. These therapeutic benefits are more evident and long-lasting compared to those obtained with rehabilitation alone.

Hypoglycemic peptide-enriched hydrolysates of Corbicula fluminea and Chlorella sorokiniana possess synergistic hypoglycemic activity through inhibiting α-glucosidase and dipeptidyl peptidase-4 activity.

BACKGROUND: The prevalence of diabetes mellitus worldwide has increased in recent decades. Maintaining the level of blood glucose is the most basic and important issue for diabetics. This study aimed to investigate the hypoglycemic activity of a combination of hypoglycemic peptide-enriched hydrolysates of Corbicula fluminea (ACH) and Chlorella sorokiniana (PCH). RESULTS: Combined supplementation of ACH and PCH synergistically inhibited α-glucosidase and DPP4 activities in vitro. After 4 weeks of treatment with ACH and/or PCH, the plasma glucose concentration and insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR), total cholesterol (TC) and triglyceride (TG) levels significantly decreased. The hypoglycemic peptides in ACH and PCH were purified and assayed for α-glucosidase and DPP4 activity. The hypoglycemic peptides in ACH and PCH effectively decreased α-glucosidase and DPP4 activities. In silico assays showed that these two peptide types have different docking poses, which determined their inhibitory effect against α-glucosidase and DPP4 activity. CONCLUSION: Combined treatment with hypoglycemic peptide-enriched ACH and PCH could modulate blood glucose by synergistically inhibiting α-glucosidase and DPP4 activities. © 2021 Society of Chemical Industry.

Oral Administration of Resveratrol-Selenium-Peptide Nanocomposites Alleviates Alzheimer's Disease-like Pathogenesis by Inhibiting Aß Aggregation and Regulating Gut Microbiota.

Alzheimer's disease (AD) is a neurodegenerative disease associated with amyloid-ß (Aß) deposition, leading to neurotoxicity (oxidative stress and neuroinflammation) and gut microbiota imbalance. Resveratrol (Res) has neuroprotective properties, but its bioavailability in vivo is very low. Herein, we developed a small Res-selenium-peptide nanocomposite to enable the application of Res for eliminating Aß aggregate-induced neurotoxicity and mitigating gut microbiota disorder in aluminum chloride (AlCl3) and d-galactose(d-gal)-induced AD model mice. Res functional selenium nanoparticles (Res@SeNPs) (8 ± 0.34 nm) were prepared first, after which the surface of Res@SeNPs was decorated with a blood-brain barrier transport peptide (TGN peptide) to generate Res-selenium-peptide nanocomposites (TGN-Res@SeNPs) (14 ± 0.12 nm). Oral administration of TGN-Res@SeNPs improves cognitive disorder through (1) interacting with Aß and decreasing Aß aggregation, effectively inhibiting Aß deposition in the hippocampus; (2) decreasing Aß-induced reactive oxygen species (ROS) and increasing activity of antioxidation enzymes in PC12 cells and in vivo; (3) down-regulating Aß-induced neuroinflammation via the nuclear factor kappa B/mitogen-activated protein kinase/Akt signal pathway in BV-2 cells and in vivo; and (4) alleviating gut microbiota disorder, particularly with respect to oxidative stress and inflammatory-related bacteria such as Alistipes, Helicobacter, Rikenella, Desulfovibrio, and Faecalibaculum. Thus, we anticipate that Res-selenium-peptide nanocomposites will offer a new potential strategy for the treatment of AD.

Lupin-Derived Bioactive Peptides: Intestinal Transport, Bioavailability and Health Benefits.

There is a renewed interest on the reliance of food-based bioactive compounds as sources of nutritive factors and health-beneficial chemical compounds. Among these food components, several proteins from foods have been shown to promote health and wellness as seen in proteins such as α/γ-conglutins from the seeds of Lupinus species (Lupin), a genus of leguminous plant that are widely used in traditional medicine for treating chronic diseases. Lupin-derived peptides (LDPs) are increasingly being explored and they have been shown to possess multifunctional health improving properties. This paper discusses the intestinal transport, bioavailability and biological activities of LDPs, focusing on molecular mechanisms of action as reported in in vitro, cell culture, animal and human studies. The potentials of several LDPs to demonstrate multitarget mechanism of regulation of glucose and lipid metabolism, chemo- and osteoprotective properties, and antioxidant and anti-inflammatory activities position LDPs as good candidates for nutraceutical development for the prevention and management of medical conditions whose etiology are multifactorial.

Discovery of a Long-Acting Parathyroid Hormone 1-34 Analogue to Treat Hypoparathyroidism.

Hypoparathyroidism (HP) is a rare disease with clinical manifestations of hypocalcemia and hyperphosphatemia, resulting from deficient or absent parathyroid hormone (PTH) secretion. Conventional treatment for patients with HP involves extensive calcium and vitamin D supplementation. In 2015, PTH1-84 was approved by the United States Food and Drug Administration as an adjunct for HP patients who cannot be well-controlled on conventional treatment. However, PTH1-84 therapy requires a daily injection, leading to poor patient compliance. The purpose of this study was to develop a long-acting PTH1-34 analogue by increasing its affinity to albumin. Three PTH1-34 variants were generated by substituting two of the three lysine (Lys) residues with arginine, reserving a single Lys as the modification site in each sequence. A series of side chains, containing fatty acid, deoxycholic acid, or biotin groups, were synthesized to modify these PTH1-34 variants by using a solid-liquid phase synthesis approach. In vitro bioactivity and albumin affinity tests were used to screen these new PTH1-34 analogues. Finally, Lys27-AAPC was selected from 69 synthesized analogues as a candidate therapeutic compound because it retained potency and exhibited a high albumin-binding capacity. In pharmacodynamic experiments, Lys27-AAPC demonstrated enhanced and prolonged efficacy in serum calcium elevating relative to PTH1-84. Moreover, a lyophilized powder for injection containing Lys27-AAPC was developed for further testing and represented a potential long-acting HP treatment.

Supplementation with a Natural Source of Amino Acids, Sil-Q1 (Silk Peptide), Enhances Natural Killer Cell Activity: A Redesigned Clinical Trial with a Reduced Supplementation Dose and Minimized Seasonal Effects in a Larger Population.

The aim of this study was to re-validate the changes in natural killer (NK) cell cytotoxicity and cytokines related to T cells after Sil-Q1 (SQ; silk peptide) supplementation in a larger pool of Korean adults with minimized daily dose of SQ and controlling seasonal influence compared to the previous study. A total of 130 subjects were randomly assigned (1:1) to consume either 7.5 g of SQ or placebo for 8 weeks. NK cell cytotoxicity and cytokines were measured at T0 (baseline) and T8 (follow-up). Comparing the NK cell cytotoxicity values at T0 and T8 within each group, the cytotoxicity at all effector cell (E) to target cell (T) ratios of 10:1, 5:1, 2.5:1, and 1.25:1 was significantly increased in the SQ group at T8. Additionally, significant differences in the changed value (Δ, subtract baseline values from follow-up values) comparison between the groups at E:T = 10:1, 5:1, and 2.5:1 were found. As a secondary endpoint, the interleukin (IL)-12 level in the SQ group was significantly increased for 8 weeks, and Δ IL-12 in the SQ group was greater than in the placebo group. In conclusion, the present study showed considerable practical implications of SQ supplementation. Thus, SQ is an effective and safe functional food supplement for enhancing immune function.

Supplementation of egg white peptides on attenuating skin mechanical damage symptoms: a promising way to accelerate wound healing process.

Recent studies have indicated that active peptides can induce an improvement in wound repair. Herein, we evaluated egg white peptides (EWPs) as a nutritional supplement to improve mechanical skin damage in BALB/c mice. Two symmetrical circular full-thickness wounds were created with 5 mm biopsy punches in the skin of the mouse dorsal region, and EWPs (200, and 400 mg kg-1) were administrated by gavage for 14 days. We analyzed the EWPs for their in vivo and in vitro antioxidant capability, toxicity, and microscopy of skin wounds, and there was no cytotoxicity or in vivo toxicity. During the period of wound healing, EWPs could promote healthy cell migration, increase serum superoxide dismutase and catalase activities and accelerate the wound healing process in a time- and dose-dependent manner, whereas the levels of malondialdehyde and reactive oxygen species showed the opposite trend. After administration with 400 mg kg-1 EWPs for 10 days, the wound had almost healed. Meanwhile, EWPs significantly enhanced serum amino acids, particularly enhancing the content of Arg, Glu, Pro, Met, and Lys, which could provide sufficient nutrition in the wound healing process. The present study demonstrates that EWPs possess a positive potential to accelerate the wound healing process of mechanical skin damage at the cellular and animal level.

Effect of one-week administration of dipeptidyl peptidase-IV inhibitory peptides from chum salmon milt on postprandial blood glucose level: a randomised, placebo-controlled, double-blind, crossover, pilot clinical trial.

Salmon milt peptide (SMP), an unused fish processing byproduct, exhibits strong inhibitory activity against dipeptidyl peptidase-IV (DPP-IV) and a suppressive effect on postprandial hyperglycaemia in Sprague-Dawley rats. Herein, we conducted a randomised, placebo-controlled, double-blind, crossover study of healthy Japanese subjects to investigate the effect of glucose loading on postprandial blood glucose levels after one week of administering continuous or single dose of 500 mg of SMP. The primary and secondary outcomes of reduced blood glucose and insulin levels were not met in the 14 subjects included in the analysis. This may be due to the ineffectiveness of SMP in insulin resistance due to its DPP-IV inhibitory activity. Therefore, we conducted a SMP subgroup analysis based on the homeostasis model assessment of insulin resistance (HOMA-IR); the group with normal HOMA-IR (<1.6) had a significantly lower area under the curve and blood glucose at 60 min after glucose loading than the group with HOMA-IR ≥1.6. These results suggest that SMP is effective in subjects without insulin resistance. There were no adverse events associated with the test food, and SMP was considered safe. This report is the first to investigate the effect of a food ingredient with DPP-IV inhibitory activity in a clinical trial.

Characterization and Safety Profile of Transfer Factors Peptides, a Nutritional Supplement for Immune System Regulation.

Imuno TF® is a nutritional supplement composed of isolated transfer factors (TF) from porcine spleen. It is composed of a specific mixture of molecules that impact functions of the biological systems and historically is linked to the immune system regulation. In this study, we demonstrate for the first time its proteomic analysis, nutritional composition, and safety profile in terms of mutagenic potential and acute oral dose (LD50). The obtained analysis indicated the product is a complex set of oligo- and polypeptides constituted of 163 different peptides which can potentially act on multiple mechanisms on the immune system pathways. The chemical composition showed low fat and low sugar content, saturated fatty acids-free, and the presence of 10 vitamins and 11 minerals. No mutagenic effect was observed, and the LD50 was 5000 mg kg-1 body weight. This accounts for a safe product to be used by the oral route, with potential benefits for the immune system.

Immunomodulatory responses in plectasin-supplemented broilers under tropical environmental conditions.

The present study was aimed to determine the immunomodulatory effects of dietary supplementation of the antimicrobial peptide (AMP) plectasin on broiler chickens. The experiment involved 300-day-old Ross chicks reared in a conventional housing system and subjected to ambient temperature and relative humidity. The birds were randomly allocated to five treatment groups: the non-supplemented negative control group (T1), enramycin-supplemented group (T2), and groups supplemented with varying doses of plectasin at 150 ppm, 300 ppm, and 450 ppm (T3, T4, and T5, respectively) from day 1 to 35. The results indicated that plectasin supplementation increased jejunal and ileal goblet cell (GC) counts, serum interferon-gamma (IFN-γ) levels at neonatal age, and serum immunoglobulin Y (IgY) titer on days 7, 21, 28, and 35. These findings confirmed that plectasin induces positive immunomodulatory responses by specifically enhancing gut mucosal barriers, early innate immunity, and humoral immune response. Specifically, supplementation at 150 ppm may be considered as the optimal dose for inclusion in broiler chicken feeds.

Synthesis and evaluation of tumor-homing peptides for targeting prostate cancer.

High toxicity caused by chemotherapeutic drugs and the acquisition of drug resistance by cancer cells are the major drawbacks in cancer therapy. A promising approach to overcome the posed barriers is conjugating tumor-homing peptides to drugs or nanocarriers. Such high-affinity peptides can specifically target surface markers overexpressed by cancer cells, ensuring a rapid and cancer-specific uptake of the drugs. Since prostate-specific membrane antigen (PSMA) is overexpressed by aggressive prostate cancer cells, targeting this surface protein with peptide conjugates can lead to the development of effective strategies against prostate cancer. In this study, we aimed to determine which PSMA-binding peptide among peptides 563, 562 and 9-mer, show the highest selectivity towards PSMA using 22Rv1 prostate cancer cells, a cell line with moderate PSMA levels. Tumor-homing peptides were synthesized by fluorenylmethoxycarbonyl-based solid-phase peptide synthesis (Fmoc-SPPS) strategy, and evaluated for their prostate cancer cell-specific targeting efficiencies by flow cytometry. Our results showed that the PSMA-binding capacity of peptide 563 was superior to those of 562, 9-mer, and 5-mer; therefore, can be utilized as a potent-targeting agent not only in the treatment of high PSMA positive but also moderate PSMA positive prostate cancer tumors.

The Influence of Specific Bioactive Collagen Peptides on Knee Joint Discomfort in Young Physically Active Adults: A Randomized Controlled Trial.

First evidence indicates that the supplementation of specific collagen peptides is associated with a significant reduction in activity-related joint pain in young adults. The purpose of the current investigation was to confirm the efficacy of the same collagen peptides in a comparable study population. In total, 180 active men and women aged between 18 and 30 years with exercise-related knee pain but no diagnosed joint disease completed the trial over a period of 12 weeks. Participants were randomly assigned to the group receiving 5 g of specific collagen peptides (CP-G) or to the placebo group (P-G). For the primary outcome, changes in pain during or after exercise from pre- to post-intervention were assessed by the participants using the Visual Analog Scale (VAS). These changes were additionally evaluated by the examining physician by means of anamnesis and physical examination of the affected knee joint. As secondary outcomes, pain under resting conditions and after 20 squats were compared between the study groups. In addition, the mobility of the knee joint and the use of alternative therapies (e.g., ointments or physiotherapy) were recorded. The supplementation of specific collagen peptides derived from type I collagen with a mean molecular weight of 3 kDa led to a significantly (p = 0.024) higher reduction of exercise-induced knee pain (-21.9 ± 18.3 mm) compared with the placebo group (-15.6 ± 18.5 mm). These findings were consistent with the physician's evaluation (-23.0 ± 19.2 mm vs. -14.6 ± 17.9 mm, p = 0.003). The decrease in pain under resting conditions and after squats did not significantly differ between the groups, as only a small number of participants suffered from pain under these conditions. Due to the clinically unremarkable baseline values, the mobility of the knee joint did not change significantly after the intervention. In conclusion, the current investigation confirmed that the oral intake of bioactive collagen peptides used in the current investigation led to a statistically significant reduction of activity-related joint pain in young active adults suffering from knee joint discomfort.

[A real-world study to evaluate a peptidic oral supplement in adults with altered intestinal function after parenteral nutrition]. / Un estudio en la vida real para evaluar un suplemento oral peptídico en adultos con alteración de la función intestinal tras la nutrición parenteral.

INTRODUCTION: Objectives: in routine clinical practice many disorders are found that can disrupt the sequence of reactions in digestion and absorption, leading to malnutrition and requiring the use of oral nutritional supplements (ONS). The objective of our study was to evaluate in a real world setting the use of and compliance with a peptide-based ONS in malnourished adult patients with intestinal compromise after more than 14 days of parenteral nutrition. Material and methods: the study was carried out in 44 malnourished patients who required total parenteral nutrition for at least 14 days without using the oral route during their hospital stay. All patients were administered, on an outpatient basis, 1 brick per day of Vital 1.5® for 12 weeks. At the beginning of treatment and after the intervention period evaluated, the following variables were collected: weight, height, body mass index (BMI), global subjective assessment test, nutritional biochemistry, 3-day nutritional survey, adverse effects generated by the formula, and completion rate. Results: 44 patients were enrolled. Mean age was 70.4 ± 10.4 years (20 women & 24 men). After the intervention the following parameters had increased: BMI (0.51 ± 0.1 kg/m2; p = 0.02), weight (1.4 ± 0.3 kg; p = 0.03), prealbumin (3.5 ± 4.1 mg/dl; p = 0.01), albumin (1.3 ± 0.1 mg/dl; p = 0.03), and transferrin (71.5 ± 24.1 mg/dl; p = 0.02). Dietary intake of the ONS represented 14.4 % of the diet's total caloric intake at 3 months, 17.5 % of carbohydrates, 12.9 % of proteins, and 12.3 % of fats. Mean compliance was 87.7 ± 7.2 % of the prescribed intakes. In relation to the nutritional situation, at the beginning of the study, 52.3 % (n = 23) of patients were in the global subjective assessment test in category B (moderate malnutrition or nutritional risk), and 47.7 % (n = 21) in category C (severe malnutrition). After the intervention, 75 % of patients were in category A (n = 33), 13.6 % (n = 6) in category B, and 11.4 % (n = 5) in category C. Conclusions: the use of a peptide-based ONS with short-chain triglycerides in outpatients showed a beneficial effect on biochemical and anthropometric parameters, and improved the nutritional status of patients with high compliance and good tolerance rates.

INTRODUCCIÓN: Objetivos: en la práctica clínica habitual existen multitud de situaciones y patologías que pueden interrumpir la digestión y la absorción intestinal, cursando con desnutrición y requiriendo el uso de suplementos orales nutricionales (SON). El objetivo de nuestro estudio fue evaluar, en el contexto de la vida real, el uso de un SON basado en péptidos, y el cumplimiento con el mismo, en pacientes adultos desnutridos con compromiso intestinal tras más de 14 días de nutrición parenteral. Material y métodos: el estudio se realizó en 44 pacientes desnutridos que requirieron nutrición parenteral total al menos 14 días, sin utilización de la vía oral durante el ingreso hospitalario. Se les administró de manera ambulatoria 1 brik al día de Vital 1.5® para su consumo durante 12 semanas. Al inicio del tratamiento y tras el periodo de intervención se les recogieron las variables siguientes: peso, talla, IMC, test de valoración subjetiva global, bioquímica nutricional, encuesta nutricional, efectos adversos generados por la fórmula y cumplimentación. Resultados: se incluyeron 44 pacientes con una edad media de 70,4 ± 10,4 años (20 mujeres/24 hombres). Tras la intervención aumentaron el IMC (0,51 ± 0,1 kg/m2; p = 0,02), el peso (1,4 ± 0,3 kg; p = 0,03), la prealbúmina (3,5 ± 4,1 mg/dl; p = 0,01), la albúmina (1,3 ± 0,1 mg/dl; p = 0,03) y la transferrina (71,5 ± 24,1 mg/dl; p = 0,02). La toma del SON represento a los 3 meses un 14,4 % del aporte calórico total de la dieta, un 17,5 % de los hidratos de carbono, un 12,9 % de las proteínas y un 12,3 % de las grasas. La cumplimentación media del grupo fue del 87,7 ± 7,2 % de las tomas prescritas. En relacion a la situacion nutricional, a la entrada del estudio un 52,3 % (n = 23) de los pacientes presentaban en el test de valoración subjetiva global la categoría B (malnutrición moderada o riesgo nutricional) y un 47,7 % (n = 21) la categoría C (desnutrición severa). Tras la intervención, un 75 % de los pacientes presentaban la categoría A (buena situación nutricional (n = 33), un 13,6 % (n = 6) de los pacientes presentaban la categoría B y un 11,4 % (n = 5) la categoría C. Conclusiones: la utilización de un suplemento peptídico con triglicéridos de cadena corta en pacientes ambulatorios tras haber recibido una nutrición parenteral total muestra un efecto beneficioso sobre los parametros bioquímicos y antropométricos, y la situación nutricional, con una alta cumplimentación y buena tolerancia.

A Global Review on Short Peptides: Frontiers and Perspectives.

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide "drugs" initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.

Elucidating Gold-MnO2 Core-Shell Nanoenvelope for Real Time SERS-Guided Photothermal Therapy on Pancreatic Cancer Cells.

Pancreatic cancer represents one of the most aggressive in nature with a miserable prognosis that warrants efficient diagnostic and therapeutic interventions. Herein, a MnO2 overlaid gold nanoparticle (AuNPs) based photothermal theranostic nanoenvelope (PTTNe:MnO2@AuNPs) was fabricated to substantiate surface-enhanced Raman spectroscopy (SERS) guided real-time monitoring of photothermal therapy (PTT) in pancreatic cancer cells. A sharp enhancement of the fingerprint Raman signature of MnO2 at 569 cm-1 exhibited as a marker peak for the first time to elucidate the intracellular PTT event. In this strategic design, the leftover bare AuNPs after the degradation of the MnO2 layer from the nanoenvelope in the presence of intracellular H2O2 enabled real-time tracking of biomolecular changes of Raman spectral variations during PTT. Moreover, the surface of the as-synthesized nanoenvelope was functionalized with a pancreatic cancer cell targeting peptide sequence for cholecystokinin fashioned the PTTNe with admirable stability and biocompatibility. Finally, the precise cell death mechanism was explicitly assessed by SERS spectral analysis as a complementary technique. This targeted phototheranostic approach demonstrated in pancreatic cancer cells presented a therapeutically viable prototype for futuristic personalized cancer nanomedicine.

Potential sealing and repair of human FM defects after trauma with peptide amphiphiles and Cx43 antisense.

OBJECTIVE: We examined whether peptide amphiphiles functionalised with adhesive, migratory or regenerative sequences could be combined with amniotic fluid (AF) to form plugs that repair fetal membrane (FM) defects after trauma and co-culture with connexin 43 (Cx43) antisense. METHODS: We assessed interactions between peptide amphiphiles and AF and examined the plugs in FM defects after trauma and co-culture with the Cx43antisense. RESULTS: Confocal microscopy confirmed directed self-assembly of peptide amphiphiles with AF to form a plug within minutes, with good mechanical properties. SEM of the plug revealed a multi-layered, nanofibrous network that sealed the FM defect after trauma. Co-culture of the FM defect with Cx43 antisense and plug increased collagen levels but reduced GAG. Culture of the FM defect with peptide amphiphiles incorporating regenerative sequences for 5 days, increased F-actin and nuclear cell contraction, migration and polarization of collagen fibers across the FM defect when compared to control specimens with minimal repair. CONCLUSIONS: Whilst the nanoarchitecture revealed promising conditions to seal iatrogenic FM defects, the peptide amphiphiles need to be designed to maximize repair mechanisms and promote structural compliance with high mechanical tolerance that maintains tissue remodeling with Cx43 antisense for future treatment.

Development of an in vivo-mimic silkworm infection model with Mycobacterium avium complex.

In vivo-mimic silkworm infection models with Mycobacterium avium and Mycobacterium intracellulare were newly established to evaluate the therapeutic effects of anti-M. avium complex (MAC) antibiotics. Silkworms raised at 37°C died within 72 hours of an injection of M. avium or M.intracellulare (2.5 × 107 colony-forming unit (CFU)/larva·g) into the hemolymph. Clinical anti-mycobacterial (tuberculosis) antibiotics were evaluated under these conditions. Clarithromycin, kanamycin, streptomycin, amikacin, and ciprofloxacin exerted therapeutic effects in a dose-dependent manner, which was consistent with those in the mouse model. Furthermore, three effective actinomycete culture broths were selected in the screening program of our microbial broth library using the silkworm model, and four active metabolites, ohmyungsamycins A and B (1 and 2), chartreusin (3), and griseoviridin (4), were identified. Among these compounds, 1 showed the lowest 50% effective dose (ED50) value (8.5 µg/larva·g), while 3 had the best ED50/minimum inhibitory concentration (MIC) ratio (7.4). These results indicate that silkworm models are a useful tool for identifying anti-MAC antibiotics candidates with veritable therapeutic effects.

Antioxidant activity and inhibition of ultraviolet radiation-induced skin damage of Selenium-rich peptide fraction from selenium-rich yeast protein hydrolysate.

The bioactive peptides and trace element selenium (Se) both have good antioxidant activity. However, whether combined Se and bioactive peptides have more excellent antioxidant activity remain unknown. The aim of this study is to prepare a Se-rich peptide fraction containing both Se and peptides from Se-rich yeast protein hydrolysate and investigated its antioxidant activity and effect on ultraviolet B (UVB) radiation-induced skin oxidative damage. The peptide fractions with different molecular weight (MW) and Se content were obtained by enzymatically hydrolyzing normal or Se-rich yeast proteins followed by a filtration process. In vitro free radical scavenging and lipid peroxidation inhibition assays showed that Se-rich peptides fraction with lower MW of <1 kDa (sSeP) had the highest antioxidant activity compared with Se-rich peptide fractions with higher MW of <3 kDa or normal peptide fractions. Oral administration of sSeP significantly decreased the level of malonaldehyde (MDA) in liver and serum, and increased the activity of glutathione peroxidase (GPx) in liver and serum in normal mice. When topically applied on the dorsal skin of mice, sSeP effectively alleviate UVB radiation-induced skin damage and oxidative stress by increasing GPx and catalase activities and glutathione content in skin or serum. Furthermore, sSeP showed a protective effect against H2O2-induced cytotoxicity in cultured human epidermal keratinocytes (HaCaT) cells probably by increasing aquaporin-3 expression and attenuating the phosphorylation of p38 MAPK. Overall, the results showed that Se-rich yeast peptide fraction containing Se and bioactive peptides could be a promising antioxidant nutrient used as food additive to enhance the body's antioxidant ability or as cosmeceutical product to minimize the skin oxidative damage.