Newly identified peptide Nigrocin-OA27 inhibits UVB induced melanin production via the MITF/TYR pathway.

Melasma is a common skin disease induced by an increase in the content of melanin in the skin, which also causes serious physical and mental harm to patients. In this research, a novel peptide (Nigrocin-OA27) from Odorrana andersonii is shown to exert a whitening effect on C57 mice pigmentation model. The peptide also demonstrated non-toxic and antioxidant capacity, and can significantly reduce melanin content in B16 cells. Topical application effectively delivered Nigrocin-OA27 to skin's epidermal and dermal layers and exhibited significant preventive and whitening effects on the UVB-induced ear pigmentation model in C57 mice. The whitening mechanism of Nigrocin-OA27 may be related to reduced levels of the microphthalmia-associated transcription factor and the key enzyme for melanogenesis-tyrosinase (TYR). Nigrocin-OA27 also inhibited the catalytic activity by adhering to the active core of TYR, thereby reducing melanin formation and deposition. In conclusion, Nigrocin-OA27 may be a potentially effective external agent to treat melasma by inhibiting aberrant skin melanin synthesis.

Identification and evaluation of a risk model predicting the prognosis of breast cancer based on characteristic signatures.

Background: Breast cancer (BC) is one of the most common fatal cancers in women. Identifying new biomarkers is thus of great significance for the diagnosis and prognosis of BC. Methods: In this study, 1,030 BC cases from The Cancer Genome Atlas (TCGA) were obtained for differential expression analysis and Short Time-series Expression Miner (STEM) analysis to identify characteristic BC development genes, which were further divided into upregulated and downregulated genes. Two predictive prognosis models were both defined by Least Absolute Shrinkage and Selection Operator (LASSO). Survival analysis and receiver operating characteristic (ROC) curve analysis were used to determine the diagnostic and prognostic capabilities of the two gene set model scores, respectively. Results: Our findings from this study suggested that both the unfavorable (BC1) and favorable (BC2) gene sets are reliable biomarkers for the diagnosis and prognosis of BC, although the BC1 model presents better diagnostic and prognostic value. Associations between the models and M2 macrophages and sensitivity to Bortezomib were also found, indicating that unfavorable BC genes are significantly involved in the tumor immune microenvironment. Conclusions: We successfully established one predictive prognosis model (BC1) based on characteristic gene sets of BC to diagnose and predict the survival time of BC patients using a cluster of 12 differentially expressed genes (DEGs).

Plant-derived exosomal nanoparticles: potential therapeutic for inflammatory bowel disease.

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a chronic autoimmune disorder characterized by inflammation. However, currently available disease-modifying anti-IBD drugs exhibit limited efficacy in IBD therapy. Furthermore, existing therapeutic approaches provide only partial relief from IBD symptoms and are associated with certain side effects. In recent years, a novel category of nanoscale membrane vesicles, known as plant-derived exosome-like nanoparticles (PDENs), has been identified in edible plants. These PDENs are abundant in bioactive lipids, proteins, microRNAs, and other pharmacologically active compounds. Notably, PDENs possess immunomodulatory, antitumor, regenerative, and anti-inflammatory properties, making them particularly promising for the treatment of intestinal diseases. Moreover, PDENs can be engineered as targeted delivery systems for the efficient transport of chemical or nucleic acid drugs to the site of intestinal inflammation. In the present study, we provided an overview of PDENs, including their biogenesis, extraction, purification, and construction strategies, and elucidated their physiological functions and therapeutic effects on IBD. Additionally, we summarized the applications and potential of PDENs in IBD treatment while highlighting the future directions and challenges in the field of emerging nanotherapeutics for IBD therapy.

OL-FS13 Alleviates Cerebral Ischemia-reperfusion Injury by Inhibiting miR-21-3p Expression.

BACKGROUND: OL-FS13, a neuroprotective peptide derived from Odorrana livida, can alleviate cerebral ischemia-reperfusion (CI/R) injury, although the specific underlying mechanism remains to be further explored. OBJECTIVE: The effect of miR-21-3p on the neural-protective effects of OL-FS13 was examined. METHODS: In this study, the multiple genome sequencing analysis, double luciferase experiment, RT-qPCR, and Western blotting were used to explore the mechanism of OL-FS13. RESULTS: Showed that over-expression of miR-21-3p against the protective effects of OL-FS13 on oxygen- glucose deprivation/re-oxygenation (OGD/R)-damaged pheochromocytoma (PC12) cells and in CI/R-injured rats. miR-21-3p was then found to target calcium/calmodulin-dependent protein kinase 2 (CAMKK2), and its overexpression inhibited the expression of CAMKK2 and phosphorylation of its downstream adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), thereby inhibiting the therapeutic effects of OL-FS13 on OGD/R and CI/R. Inhibition of CAMKK2 also antagonized up-regulated of nuclear factor erythroid 2-related factor 2 (Nrf-2) by OL-FS13, thereby abolishing the antioxidant activity of the peptide. CONCLUSION: Our results showed that OL-FS13 alleviated OGD/R and CI/R by inhibiting miR-21-3p to activate the CAMKK2/AMPK/Nrf-2 axis.

Stem Cell Therapy in Inflammatory Bowel Disease: A Review of Achievements and Challenges.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a group of chronic inflammatory diseases of the gastrointestinal tract. Repeated inflammation can lead to complications, such as intestinal fistula, obstruction, perforation, and bleeding. Unfortunately, achieving durable remission and mucosal healing (MH) with current treatments is difficult. Stem cells (SCs) have the potential to modulate immunity, suppress inflammation, and have anti-apoptotic and pro-angiogenic effects, making them an ideal therapeutic strategy to target chronic inflammation and intestinal damage in IBD. In recent years, hematopoietic stem cells (HSCs) and adult mesenchymal stem cells (MSCs) have shown efficacy in treating IBD. In addition, numerous clinical trials have evaluated the efficiency of MSCs in treating the disease. This review summarizes the current research progress on the safety and efficacy of SC-based therapy for IBD in both preclinical models and clinical trials. We discuss potential mechanisms of SC therapy, including tissue repair, paracrine effects, and the promotion of angiogenesis, immune regulation, and anti-inflammatory effects. We also summarize current SC engineering strategies aimed at enhancing the immunosuppressive and regenerative capabilities of SCs for treating intestinal diseases. Additionally, we highlight current limitations and future perspectives of SC-related therapy for IBD.

A short peptide exerts neuroprotective effects on cerebral ischemia-reperfusion injury by reducing inflammation via the miR-6328/IKKß/NF-κB axis.

BACKGROUND: Despite considerable efforts, ischemic stroke (IS) remains a challenging clinical problem. Therefore, the discovery of effective therapeutic and targeted drugs based on the underlying molecular mechanism is crucial for effective IS treatment. METHODS: A cDNA-encoding peptide was cloned from RNA extracted from Rana limnocharis skin, and the mature amino acid sequence was predicted and synthesized. Hemolysis and acute toxicity of the peptide were tested. Furthermore, its neuroprotective properties were evaluated using a middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats and an oxygen-glucose deprivation/reperfusion (OGD/R) model in neuron-like PC12 cells. The underlying molecular mechanisms were explored using microRNA (miRNA) sequencing, quantitative real-time polymerase chain reaction, dual-luciferase reporter gene assay, and western blotting. RESULTS: A new peptide (NP1) with an amino acid sequence of 'FLPAAICLVIKTC' was identified. NP1 showed no obvious toxicities in vivo and in vitro and was able to cross the blood-brain barrier. Intraperitoneal administration of NP1 (10 nmol/kg) effectively reduced the volume of cerebral infarction and relieved neurological dysfunction in MCAO/R model rats. Moreover, NP1 significantly alleviated the decrease in viability and increase in apoptosis of neuron-like PC12 cells induced by OGD/R. NP1 effectively suppressed inflammation by reducing interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) levels in vitro and in vivo. Furthermore, NP1 up-regulated the expression of miR-6328, which, in turn, down-regulated kappa B kinase ß (IKKß). IKKß reduced the phosphorylation of nuclear factor-kappa B p65 (NF-κB p65) and inhibitor of NF-κB (I-κB), thereby inhibiting activation of the NF-κB pathway. CONCLUSIONS: The newly discovered non-toxic peptide NP1 ('FLPAAICLVIKTC') exerted neuroprotective effects on cerebral ischemia-reperfusion injury by reducing inflammation via the miR-6328/IKKß/NF-κB axis. Our findings not only provide an exogenous peptide drug candidate and endogenous small nucleic acid drug candidate but also a new drug target for the treatment of IS. This study highlights the importance of peptides in the development of new drugs, elucidation of pathological mechanisms, and discovery of new drug targets.

Scorpion venom peptide HsTx2 suppressed PTZ-induced seizures in mice via the circ_0001293/miR-8114/TGF-ß2 axis.

BACKGROUND: Due to the complexity of the mechanisms involved in epileptogenesis, the available antiseizure drugs (ASDs) do not meet clinical needs; hence, both the discovery of new ASDs and the elucidation of novel molecular mechanisms are very important. METHODS: BALB/c mice were utilized to establish an epilepsy model induced by pentylenetetrazol (PTZ) administration. The peptide HsTx2 was administered for treatment. Primary astrocyte culture, immunofluorescence staining, RNA sequencing, identification and quantification of mouse circRNAs, cell transfection, bioinformatics and luciferase reporter analyses, enzyme-linked immunosorbent assay, RNA extraction and reverse transcription-quantitative PCR, Western blot and cell viability assays were used to explore the potential mechanism of HsTx2 via the circ_0001293/miR-8114/TGF-ß2 axis. RESULTS: The scorpion venom peptide HsTx2 showed an anti-epilepsy effect, reduced the inflammatory response, and improved the circular RNA circ_0001293 expression decrease caused by PTZ in the mouse brain. Mechanistically, in astrocytes, circ_0001293 acted as a sponge of endogenous microRNA-8114 (miR-8114), which targets transforming growth factor-beta 2 (TGF-ß2). The knockdown of circ_0001293, overexpression of miR-8114, and downregulation of TGF-ß2 all reversed the anti-inflammatory effects and the influence of HsTx2 on the MAPK and NF-κB signaling pathways in astrocytes. Moreover, both circ_0001293 knockdown and miR-8114 overexpression reversed the beneficial effects of HsTx2 on inflammation, epilepsy progression, and the MAPK and NF-κB signaling pathways in vivo. CONCLUSIONS: HsTx2 suppressed PTZ-induced epilepsy by ameliorating inflammation in astrocytes via the circ_0001293/miR-8114/TGF-ß2 axis. Our results emphasized that the use of exogenous peptide molecular probes as a novel type of ASD, as well as to explore the novel endogenous noncoding RNA-mediated mechanisms of epilepsy, might be a promising research area.

Peptide OM-LV20 protects astrocytes against oxidative stress via the 'PAC1R/JNK/TPH1' axis.

Stroke can lead to severe nerve injury and debilitation, resulting in considerable social and economic burdens. Due to the high complexity of post-injury repair mechanisms, drugs approved for use in stroke are extremely scarce, and thus, the discovery of new antistroke drugs and targets is critical. Tryptophan hydroxylase 1 (TPH1) is involved in a variety of mental and neurobehavioral processes, but its effects on stroke have not yet been reported. Here, we used primary astrocyte culture, quantitative real-time PCR, double immunofluorescence assay, lentiviral infection, cell viability analysis, Western blotting, and other biochemical experiments to explore the protective mechanism of peptide OM-LV20, which previously exhibited neuroprotective effects in rats after ischemic stroke via a mechanism that may involve TPH1. First, we showed that TPH1 was expressed in rat astrocytes. Next, we determined that OM-LV20 impacted expression changes of TPH1 in CTX-TNA2 cells and exhibited a protective effect on the decrease in cell viability and catalase (CAT) levels induced by hydrogen peroxide. Importantly, we also found that TPH1 expression induced by OM-LV20 may be related to the level of change in the pituitary adenylate cyclase-activating peptide type 1 receptor (PAC1R) and to the JNK signaling pathways, thereby exerting a protective effect on astrocytes against oxidative stress. The protective effects of OM-LV20 likely occur via the 'PAC1R/JNK/TPH1' axis, thus highlighting TPH1 as a novel antistroke drug target.

Short Hexapeptide Optimized from Rice-Derived Peptide 1 Shows Promising Anti-hyperuricemia Activities.

Plant-derived peptides are a treasure trove for new-generation anti-hyperuricemia drugs. In the current study, we optimized a short hexapeptide rice-derived peptide 1 (RDP1)-M3 (AAAAGA) according to the anti-hyperuricemia RDP1 peptide identified from rice in our previous research. Results showed that RDP1-M3 exerted better hyperuricemia-alleviating and xanthine oxidase (XOD)-inhibiting potency in mice than RDP1. The biodistribution of RDP1-M3 was also analyzed. RDP1-M3 directly decreased XOD and uric acid levels in vivo and in vitro. In addition, RDP1-M3 reduced the expression of urate transporter 1 and glucose transporter 9, increased the level of organic anion transporter 1, reduced the expression of NOD-like receptor superfamily pyrin 3 inflammasomes, and reduced the levels of interleukin-1ß and tumor necrosis factor-α of hyperuricemic mice. Thus, our results indicated that the optimized short hexapeptide RDP1-M3 may be a candidate drug for anti-hyperuricemia.

A new peptide originated from amphibian skin alleviates the ultraviolet B-induced skin photodamage.

Although amphibian-derived bioactive peptides have attracted increasing attention for their potential use in the treatment of photodamage, research is still in its infancy. In this study, we obtained a new antioxidant peptide, named OA-GI13 (GIWAPWPPRAGLC), from the skin of the odorous frog Odorrana andersonii and determined its effects on ultraviolet B (UVB)-induced skin photodamage as well as its possible molecular mechanisms. Results showed that OA-GI13 directly scavenged free radicals, maintained the viability of hydrogen peroxide-challenged keratinocytes, promoted the release of superoxide dismutase, catalase, and glutathione, and reduced the level of lactate dehydrogenase. Furthermore, topical application of OA-GI13 in mice alleviated dorsal skin erythema and edema and protected the skin against UVB irradiation by increasing antioxidant levels and decreasing peroxide, malondialdehyde, and 8-hydroxydeoxyguanosine levels. OA-GI13 also alleviated oxidative stress injury in vivo and in vitro, possibly by inhibiting p38 protein phosphorylation. Our study confirmed the anti-photodamage effects of this novel amphibian-derived peptide, thus providing a new molecule for the development of drugs and topical agents for the treatment of skin photodamage.

Peptide OM-LV20 promotes structural and functional recovery of spinal cord injury in rats.

At present, there are no satisfactory therapeutic drugs for the functional recovery of spinal cord injury (SCI). We previously identified a novel peptide (OM-LV20) that accelerated the regeneration of injured skin tissues of mice and exerts neuroprotective effects against cerebral ischemia/reperfusion injury in rats. Here, the intraperitoneal injection of OM-LV20 (1 µg/kg) markedly improved motor function recovery in the hind limbs of rats with traumatic SCI, and further enhanced spinal cord repair. Administration of OM-LV20 increased the number of surviving neuron bodies, as well as the expression levels of brain-derived neurotrophic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB). In the acute stage of SCI, OM-LV20 treatment also increased superoxide dismutase and glutathione content but decreased the levels of malonaldehyde and nitric oxide. Thus, OM-LV20 significantly promoted structural and functional recovery of SCI in adult rats by increasing neuronal survival and BDNF and TrkB expression, and thereby regulating the balance of oxidative stress. Based on our knowledge, this research is the first report on the effects of amphibian-derived peptide on the recovery of SCI and our results highlight the potential of peptide OM-LV20 administration in the acceleration of the recovery of SCI.

Optimal Timing of Simethicone Supplement for Bowel Preparation: A Prospective Randomized Controlled Trial.

Background and Aims: Simethicone (SIM), as an antifoaming agent, has been shown to improve bowel preparation during colonoscopy. However, the optimal timing of SIM addition remained undetermined. We aimed to investigate the optimal timing of SIM addition to polyethylene glycol (PEG) to improve bowel preparation. Methods: Eligible patients were randomly assigned to two groups: the SIM evening group (SIM addition to PEG in the evening of the day prior to colonoscopy) and the SIM morning group (SIM addition to PEG in the morning of colonoscopy). The primary outcome was Bubble Scale (BS). The secondary outcomes were Boston Bowel Preparation Scale (BBPS) and adenoma detection rate (ADR). Results: A total of 419 patients were enrolled in this study. The baseline characteristics of the patients were similar in both groups. No significant differences were observed in terms of BS (8.76 ± 0.90 vs. 8.65 ± 1.16, P = 0.81), ADR (34.1% vs. 30.8%, P = 0.47), Boston Bowel Preparation Scale (BBPS) (8.59 ± 0.94 vs. 8.45 ± 1.00, P = 0.15), and withdrawal time (8.22 ± 2.04 vs. 8.01 ± 2.51, P = 0.094) between the two groups. Moreover, safety and compliance were similar in both groups. However, the SIM evening group was associated with shorter cecal intubation time (3.80 ± 1.81 vs. 4.42 ± 2.03, P < 0.001), higher BS (2.95 ± 0.26 vs. 2.88 ± 0.38, P = 0.04) in the right colon, and diminutive ADR (62.5% vs. 38.6%, P = 0.022) in the right colon, when compared to the SIM evening group. Conclusions: The SIM addition to PEG in the evening of the day prior to colonoscopy can shorten cecal intubation time and improve BS scores and diminutive ADR of the right colon compared with the SIM addition to PEG in the morning of colonoscopy in bowel preparation.

Comprehensive analysis on the expression profile and prognostic values of Synaptotagmins (SYTs) family members and their methylation levels in gastric cancer.

Synaptotagmins (SYTs), constitute a family of 17 membrane-trafficking protein, palying crucial roles in the development and progression of human cancers. However, only very few studies have investigated the expression profile and prognostic values of SYTs family members in gastric cancer (GC). Therefore, we comprehensively evaluated the expression, methylation, prognosis and immune significance of SYTs family members through bioinformatics analysis from the online databases in GC. The expressions of SYT4, SYT9, and SYT14 were up-regulated, and negatively associated with their methylation levels in GC. Both the over-expression of SYT4, SYT9 and SYT14 and their hypomethylation levels contributed to an unsatisfactory overall survival (OS) and progression-free survival (PFS) in GC. Moreover, the low expressions of several methylation cg sites (cg02795029, cg07581146, cg15149095, cg19922137, cg25371503, cg26158959, cg02269161, cg03226737, cg08185661, cg16437728, cg22723056 and cg24678137) were significantly correlated with an unfavorable OS and PFS in GC. Furthermore, the expression of SYT4, SYT9 and SYT14 played a pivotal role in immune cells infiltration in GC. Collectively, our current finding suggested that SYT4, SYT9 and SYT14 might be potent prognostic indictors and promising immunotherapeutic targets for GC patients.

Discovery of a novel short peptide with efficacy in accelerating the healing of skin wounds.

Despite extensive efforts to develop efficacious therapeutic approaches, the treatment of skin wounds remains a considerable clinical challenge. Existing remedies cannot sufficiently meet current needs, so the discovery of novel pro-healing agents is of growing importance. In the current research, we identified a novel short peptide (named RL-QN15, primary sequence 'QNSYADLWCQFHYMC') from Rana limnocharis skin secretions, which accelerated wound healing in mice. Exploration of the underlying mechanisms showed that RL-QN15 activated the MAPK and Smad signaling pathways, and selectively modulated the secretion of cytokines from macrophages. This resulted in the proliferation and migration of skin cells and dynamic regulation of TGF-ß1 and TGF-ß3 in wounds, which accelerated re-epithelialization and granulation tissue formation and thus skin regeneration. Moreover, RL-QN15 showed significant therapeutic potency against chronic wounds, skin fibrosis, and oral ulcers. Our results highlight frog skin secretions as a potential treasure trove of bioactive peptides with healing activity. The novel peptide (RL-QN15) identified in this research shows considerable capacity as a candidate for the development of novel pro-healing agents.

Peptide OM-LV20 exerts neuroprotective effects against cerebral ischemia/reperfusion injury in rats.

Ischemia/reperfusion (I/R) is a common injury leading to ischemic stroke. At present, I/R treatment remains limited, highlighting the urgent need for the discovery and development of new protective drugs for brain injury. Here, we investigated the neuroprotective effects of short peptide OM-LV20 previously identified from amphibian against I/R rats. Results showed that intraperitoneal administration of OM-LV20 (20 ng/kg) significantly reduced infarct area formation, improved behavioral abnormalities, and protected cortical and hippocampal neurons against death caused by I/R. Moreover, the underlying molecular mechanism was involved with the regulation of the MAPK and BDNF/AKT signaling pathways, as well as the levels of cyclic adenosine monophosphate, pituitary adenylate cyclase-activating polypeptide receptor, and tryptophan hydroxylase 1. To the best of our knowledge, this research was the first report to describe the neuroprotective effects of an amphibian skin secretion-derived peptide in I/R rats and highlighted OM-LV20 as a promising drug candidate for the development of novel anti-stroke therapies.

Metabolic Reprogramming in Gastric Cancer: Trojan Horse Effect.

Worldwide, gastric cancer (GC) represents the fifth most common cancer for incidence and the third leading cause of death in developed countries. Despite the development of combination chemotherapies, the survival rates of GC patients remain unsatisfactory. The reprogramming of energy metabolism is a hallmark of cancer, especially increased dependence on aerobic glycolysis. In the present review, we summarized current evidence on how metabolic reprogramming in GC targets the tumor microenvironment, modulates metabolic networks and overcomes drug resistance. Preclinical and clinical studies on the combination of metabolic reprogramming targeted agents and conventional chemotherapeutics or molecularly targeted treatments [including vascular endothelial growth factor receptor (VEGFR) and HER2] and the value of biomarkers are examined. This deeper understanding of the molecular mechanisms underlying successful pharmacological combinations is crucial in finding the best-personalized treatment regimens for cancer patients.

The efficacy and safety of underwater endoscopic mucosal resection for ≥10-mm colorectal polyps: systematic review and meta-analysis.

BACKGROUND: Underwater endoscopic mucosal resection (UEMR) is a promising strategy for nonpedunculated colorectal polyp removal. However, the efficacy and safety of the technique for the treatment of ≥ 10-mm colorectal polyps remain unclear. We aimed to comprehensively assess the efficacy and safety of UEMR for polyps sized 10-19 mm and ≥ 20 mm. METHODS: PubMed, EMBASE, and the Cochrane Library databases were searched for relevant articles from January 2012 to November 2019. Primary outcomes were the rates of adverse events and residual polyps. Secondary outcomes were the complete resection, en bloc resection, and R0 resection rates. RESULTS: 18 articles including 1142 polyps from 1093 patients met our inclusion criteria. The overall adverse event and residual polyp rates were slightly lower for UEMR when removing colorectal polyps of 10-19 mm vs. ≥ 20 mm (3.5 % vs. 4.3 % and 1.2 % vs. 2.6 %, respectively). The UEMR-related complete resection rate was slightly higher for colorectal polyps of 10-19 mm vs. ≥ 20 mm (97.9 % vs. 92.0 %). However, the en bloc and R0 resection rates were dramatically higher for UEMR removal of polyps of 10-19 mm vs. ≥ 20 mm (83.4 % vs. 36.1 % and 73.0 % vs. 40.0 %, respectively). In addition, univariate meta-regression revealed that polyp size was an independent predictor for complete resection rate (P = 0.03) and en bloc resection (P = 0.01). CONCLUSIONS: UEMR was an effective and safe technique for the removal of ≥ 10-mm nonpedunculated colorectal polyps. However, UEMR exhibited low en bloc and R0 resection rates for the treatment of ≥ 20-mm polyps.

Discovery of a novel rice-derived peptide with significant anti-gout potency.

As a metabolic disease, gout, which seriously affects the normal life of patients, has become increasingly common in modern society. However, the existing medicines cannot completely meet the clinical needs. In the current study, a novel short peptide (named rice-derived-peptide-2 (RDP2), AAAAGAMPK-NH2, 785.97 Da) was isolated and identified from water extract of shelled Oryza sativa fruits, without toxic side effects but excellent stability. Our results indicated that RDP2 (the minimum effective concentration is 5 µg kg-1) induced a significant reduction in serum uric acid levels in hyperuricemic mice via suppressing xanthine oxidase activity and urate transporter 1 expression, as well as alleviated renal damage through inhibiting the activation of NLRP3 inflammasome. In addition, RDP2 can also alleviate paw swelling and inflammatory reactions in mice after subcutaneous injection of monosodium urate crystals. As mentioned above, we obtained a novel peptide which could work through all stages of gout, not only reducing uric acid levels and renal damage in hyperuricemic mice, but also alleviating inflammatory responses associated with acute gout attack, and thus provided a new peptide molecular template for the development of anti-gout drugs.

RDP3, A Novel Antigout Peptide Derived from Water Extract of Rice.

Gout and hyperuricemia can seriously affect the quality of life; at present, however, existing medicines are unable to meet all clinical needs. In the current study, a novel peptide (i.e., rice-derived-peptide-3 (RDP3), AAAAMAGPK-NH2, 785.97 Da) in water extract obtained from shelled Oryza sativa fruits was identified. Testing revealed that RDP3 (minimum effective concentration 100 µg/kg) did not show both hemolytic and acute toxicity, and reduced uric acid levels in the serum of hyperuricemic mice by inhibiting xanthine oxidase activity and decreasing urate transporter 1 expression. RDP3 also alleviated renal injury in hyperuricemic mice by decreasing NLRP3 inflammasome expression. Furthermore, RDP3 alleviated formalin-induced paw pain and reduced monosodium urate crystal-induced paw swelling and inflammatory factors in mice. Thus, this newly identified peptide reduced uric acid levels and renal damage in hyperuricemic mice and showed anti-inflammatory and analgesic activities, indicating the potential of RDP3 as an antigout medicine candidate.

Bioinformatic Analysis Suggests That Three Hub Genes May Be a Vital Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide due to its ineffective diagnosis and poor prognosis. It is essential to identify differentially expressed genes (DEGs) in PDAC to gain new insights into its underlying molecular mechanisms, as well as identify potential diagnostic and therapeutic targets. We screened 135 DEGs from the GSE15417, GSE16515, and GSE28735 PDAC and normal pancreatic tissue microarray data sets, and identified 16 DEGs that were correlated with PDAC prognosis through the Kaplan-Meier survival analysis and log-rank tests. The Cancer Genome Atlas and Oncomine databases validated the expression levels of 16 candidate genes (SLC6A14, GPRC5A, IFI27, ERP27, SDR16C5, SIDT2, TCN1, COL12A1, MMP1, CEACAM6, DKK1, ITGA2, KRT19, PLAU, ANO1, and GABRP). Weighted gene coexpression network analysis (WGCNA) and protein and protein interaction (PPI) analysis identified three hub genes-ERP27, ITGA2, and MMP1-that are likely important in PDAC prognosis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that they were enriched in functions of extracellular matrix organization, extracellular structure organization, and positive regulation of cell migration. Taken together, we identified three pivotal genes for PDAC, which can improve our understanding of its pathogenesis, progression, and prognosis.