Harnessing the health benefits of purple and yellow-fleshed sweet potatoes: Phytochemical composition, stabilization methods, and industrial utilization- A review.

Purple-fleshed sweet potato (PFSP) and yellow-fleshed sweet potato (YFSP) are crops highly valued for their nutritional benefits and rich bioactive compounds. These compounds include carotenoids, flavonoids (including anthocyanins), and phenolic acids etc. which are present in both the leaves and roots of these sweet potatoes. PFSP and YFSP offer numerous health benefits, such as antioxidant, anti-inflammatory, anti-cancer, and neuroprotective properties. The antioxidant activity of these sweet potatoes holds significant potential for various industries, including food, pharmaceutical, and cosmetics. However, a challenge in utilizing PFSP and YFSP is their susceptibility to rapid oxidation and color fading during processing and storage. To address this issue and enhance the nutritional value and shelf life of food products, researchers have explored preservation methods such as co-pigmentation and encapsulation. While YFSP has not been extensively studied, this review provides a comprehensive summary of the nutritional value, phytochemical composition, health benefits, stabilization techniques for phytochemical, and industrial applications of both PFSP and YFSP in the food industry. Additionally, the comparison between PFSP and YFSP highlights their similarities and differences, shedding light on their potential uses and benefits in various food products.

Role of M6a Methylation in Myocardial Ischemia-Reperfusion Injury and Doxorubicin-Induced Cardiotoxicity.

Cardiovascular disease remains the leading cause of death worldwide, with acute myocardial infarction and anticancer drug-induced cardiotoxicity being the significant factors. The most effective treatment for acute myocardial infarction is rapid restoration of coronary blood flow by thrombolytic therapy or percutaneous coronary intervention. However, myocardial ischemia-reperfusion injury (MI/RI) after reperfusion therapy is common in acute myocardial infarction, thus affecting the prognosis of patients with acute myocardial infarction. There is no effective treatment for MI/RI. Anthracyclines such as Doxorubicin (DOX) have limited clinical use due to their cardiotoxicity, and the mechanism of DOX-induced cardiac injury is complex and not yet fully understood. N6-methyladenosine (m6A) plays a crucial role in many biological processes. Emerging evidence suggests that m6A methylation plays a critical regulatory role in MI/RI and DOX-induced cardiotoxicity (DIC), suggesting that m6A may serve as a novel biomarker and therapeutic target for MI/RI and DIC. M6A methylation may mediate the pathophysiological processes of MI/RI and DIC by regulating cellular autophagy, apoptosis, oxidative stress, and inflammatory response. In this paper, we first focus on the relationship between m6A methylation and MI/RI, then further elucidate that m6A methylation may mediate the pathophysiological process of MI/RI through the regulation of cellular autophagy, apoptosis, oxidative stress, and inflammatory response. Finally, briefly outline the roles played by m6A in DIC, which will provide a new methodology and direction for the research and treatment of MI/RI and DIC.

Apple pectin-based active films to preserve oil: Effects of naturally branched phytoglycogen-curcumin host.

Pectin has excellent film-forming properties, but its functional properties need to be enhanced. Therefore, we constructed naturally branched phytoglycogen (PG) nanoparticles to solubilize curcumin (CCM) and further enhance the properties of apple pectin-based active films. The size of the PG spherical particles ranged from 30 to 100 nm with some aggregates. The branch density of the PG was 6.02 %. These PG nanoparticles increased the solubility of CCM nearly 1742-fold and a nanosized phytoglycogen-curcumin (PG-CCM) host was formed via hydrogen bonding and hydrophobic interaction. This host promoted the formation of pectin-based films with a dense structure and increased their tensile strength to 23.51 MPa. The coefficient to water vapor permeability, oxygen permeability and carbon dioxide permeability were all decreased indicating their barrier performance were improved. Among them, the oxygen permeability coefficient decreased most, from 1.14 × 10-7 g·m-1·s-1 to 0.8 × 10-7 g·m-1·s-1. Also, the transmittance of the active film at 280 nm and 660 nm decreased to 0.65 % and 72.10 %. Antioxidant and antibacterial properties were significantly enhanced (P < 0.05). And the results showed this film was an excellent oil packaging material. The active film incorporating PG-CCM host can replace heat-sealed plastic bags/pouch made from polyethylene and polypropylene synthetic plastics, and solve the problem that plastic packaging is difficult to degrade and cannot be squeezed clean. This provides a new conceptual framework for developing pectin-based active films by incorporating of PG and CCM.

Unveiling the Diversity and Modifications of Short Peptides in Buthus martensii Scorpion Venom through Liquid Chromatography-High Resolution Mass Spectrometry.

More recently, short peptides in scorpion venom have received much attention because of their potential for drug discovery. Although various biological effects of these short peptides have been found, their studies have been hindered by the lack of structural information especially in modifications. In this study, small peptides from scorpion venom were investigated using high-performance liquid chromatography high-resolution mass spectrometry followed by de novo sequencing. A total of 156 sequences consisting of 2~12 amino acids were temporarily identified from Buthus martensii scorpion venom. The identified peptides exhibited various post-translational modifications including N-terminal and C-terminal modifications, in which the N-benzoyl modification was first found in scorpion venom. Moreover, a short peptide Bz-ARF-NH2 demonstrated both N-terminal and C-terminal modifications simultaneously, which is extremely rare in natural peptides. In conclusion, this study provides a comprehensive insight into the diversity, modifications, and potential bioactivities of short peptides in scorpion venom.

An Oral Nanomedicine Elicits In Situ Vaccination Effect against Colorectal Cancer.

Oral administration is the most preferred approach for treating colon diseases, and in situ vaccination has emerged as a promising cancer therapeutic strategy. However, the lack of effective drug delivery platforms hampered the application of in situ vaccination strategy in oral treatment of colorectal cancer (CRC). Here, we construct an oral core-shell nanomedicine by preparing a silk fibroin-based dual sonosensitizer (chlorin e6, Ce6)- and immunoadjuvant (imiquimod, R837)-loaded nanoparticle as the core, with its surface coated with plant-extracted lipids and pluronic F127 (p127). The resultant nanomedicines (Ce6/R837@Lp127NPs) maintain stability during their passage through the gastrointestinal tract and exert improved locomotor activities under ultrasound irradiation, achieving efficient colonic mucus infiltration and specific tumor penetration. Thereafter, Ce6/R837@Lp127NPs induce immunogenic death of colorectal tumor cells by sonodynamic treatment, and the generated neoantigens in the presence of R837 serve as a potent in situ vaccine. By integrating with immune checkpoint blockades, the combined treatment modality inhibits orthotopic tumors, eradicates distant tumors, and modulates intestinal microbiota. As the first oral in situ vaccination, this work spotlights a robust oral nanoplatform for producing a personalized vaccine against CRC.

Characterization, antioxidant activity and potential application fractionalized Szechuan pepper on fresh beef meat as natural preservative.

The pericarp of Szechuan pepper is rich in phenols and alkylamides, making it a potential source of antioxidant compounds. Despite being recognized as the primary antioxidants in Szechuan pepper, there is still limited knowledge about their application in real food systems. This study aims to identify, separate, and apply polyphenol and alkylamide fractions derived from Szechuan extracts to beef meat. Using HPLC-MS2, we identified 5 phenols and 11 alkylamides in Szechuan extracts. The quality of the minced meat was evaluated based on color, thiobarbituric acid reactive substances (TBARS), conjugated dienes, carbonyl content, Sulfhydryl content, microbiological content, and total volatile basic nitrogen content (TVB-N). Compared to the polyphenol fraction (1.25 mg/mL), alkylamide fraction (25 mg/mL), and control samples, beef samples incorporated with the polyphenol fraction (6.25 mg/mL) significantly reduced carbonyl content, TBARS, and TVB-N values at the end of storage. Furthermore, they exhibited a significant slowdown in microbial development, improved meat color stability, and preserved pH. Therefore, the use of Szechuan pepper fractions as natural preservatives in meat and meat products is an important area of research and has the potential to enhance the safety and quality of meat products.

m6A modification-tuned sphingolipid metabolism regulates postnatal liver development in male mice.

Different organs undergo distinct transcriptional, epigenetic and physiological alterations that guarantee their functional maturation after birth. However, the roles of epitranscriptomic machineries in these processes have remained elusive. Here we demonstrate that expression of RNA methyltransferase enzymes Mettl3 and Mettl14 gradually declines during postnatal liver development in male mice. Liver-specific Mettl3 deficiency causes hepatocyte hypertrophy, liver injury and growth retardation. Transcriptomic and N6-methyl-adenosine (m6A) profiling identify the neutral sphingomyelinase, Smpd3, as a target of Mettl3. Decreased decay of Smpd3 transcripts due to Mettl3 deficiency results in sphingolipid metabolism rewiring, characterized by toxic ceramide accumulation and leading to mitochondrial damage and elevated endoplasmic reticulum stress. Pharmacological Smpd3 inhibition, Smpd3 knockdown or Sgms1 overexpression that counteracts Smpd3 can ameliorate the abnormality of Mettl3-deficent liver. Our findings demonstrate that Mettl3-N6-methyl-adenosine fine-tunes sphingolipid metabolism, highlighting the pivotal role of an epitranscriptomic machinery in coordination of organ growth and the timing of functional maturation during postnatal liver development.

Physician-Modified Endovascular Graft for Left Subclavian Artery Fenestration during Thoracic Endovascular Aortic Repair.

BACKGROUND: This study aimed to evaluate the safety and efficacy of physician-modified endovascular graft for preservation of left subclavian artery during thoracic endovascular aortic repair. METHODS: From June 2019 to October 2022, 66 patients with a variety of thoracic aortic pathologies were treated with thoracic endovascular aortic repair using physician-modified endovascular graft left subclavian artery fenestration to achieve adequate proximal landing zone. The details of surgical techniques were described. The perioperative morbidity, mortality, and the outcomes of mid-term follow-up were analyzed. RESULTS: Of the 66 patients (men: women, 53:13; age, 55.18 [55.18 ± 10.62] years), 53 (80.30%) presented with type B aortic dissection, 10 (15.15%) with thoracic penetrating aortic ulcer, 2 (3.03%) with thoracic aortic aneurysm, and 1 (1.52%) with left subclavian artery aneurysm. All of them underwent thoracic endovascular aortic repair using physician-modified endovascular graft left subclavian artery fenestration on the sterile back table. The technique success rate was 96.97% (n = 64). Total operation time was 92 min (interquartile range, 86-118), graft modification time was 19 min (interquartile range, 17-21), fluoroscopy time was 49 min (interquartile range, 41-62), and contrast agent dosage was 165 mL (interquartile range, 155-185). 30-day perioperative morbidities were 3 (4.55%) strokes, 1 (1.52%) retrograde type A aortic dissection, 1 (1.52%) aortic intimal intussusception, 1 (1.52%) left arm ischemia, and 3 (4.55%) type Ia endoleaks. Postoperative 30-day mortality and reintervention rates were 1.52% and 4.55%, respectively. Among the 63 patients included in the follow-up of 17 months (interquartile range, 7.75-18.25), the primary patency of left subclavian artery fenestration stents was 100%. Late complications were 1 (1.59%) distal stent graft-induced new entry and 1 (1.59%) death due to retrograde type A aortic dissection during the follow-up. The stent graft-induced new entry patient was observed with stable false lumen. CONCLUSIONS: Thoracic endovascular aortic repair with physician-modified endovascular graft for left subclavian artery revascularization is a safe, feasible, and efficacious technique associated with high success rate. Further study is needed for long-term outcome investigation.

DeepsmirUD: Prediction of Regulatory Effects on microRNA Expression Mediated by Small Molecules Using Deep Learning.

Aberrant miRNA expression has been associated with a large number of human diseases. Therefore, targeting miRNAs to regulate their expression levels has become an important therapy against diseases that stem from the dysfunction of pathways regulated by miRNAs. In recent years, small molecules have demonstrated enormous potential as drugs to regulate miRNA expression (i.e., SM-miR). A clear understanding of the mechanism of action of small molecules on the upregulation and downregulation of miRNA expression allows precise diagnosis and treatment of oncogenic pathways. However, outside of a slow and costly process of experimental determination, computational strategies to assist this on an ad hoc basis have yet to be formulated. In this work, we developed, to the best of our knowledge, the first cross-platform prediction tool, DeepsmirUD, to infer small-molecule-mediated regulatory effects on miRNA expression (i.e., upregulation or downregulation). This method is powered by 12 cutting-edge deep-learning frameworks and achieved AUC values of 0.843/0.984 and AUCPR values of 0.866/0.992 on two independent test datasets. With a complementarily constructed network inference approach based on similarity, we report a significantly improved accuracy of 0.813 in determining the regulatory effects of nearly 650 associated SM-miR relations, each formed with either novel small molecule or novel miRNA. By further integrating miRNA-cancer relationships, we established a database of potential pharmaceutical drugs from 1343 small molecules for 107 cancer diseases to understand the drug mechanisms of action and offer novel insight into drug repositioning. Furthermore, we have employed DeepsmirUD to predict the regulatory effects of a large number of high-confidence associated SM-miR relations. Taken together, our method shows promise to accelerate the development of potential miRNA targets and small molecule drugs.

Tea leaf-derived exosome-like nanotherapeutics retard breast tumor growth by pro-apoptosis and microbiota modulation.

While several artificial nanodrugs have been approved for clinical treatment of breast tumor, their long-term applications are restricted by unsatisfactory therapeutic outcomes, side reactions and high costs. Conversely, edible plant-derived natural nanotherapeutics (NTs) are source-widespread and cost-effective, which have been shown remarkably effective in disease treatment. Herein, we extracted and purified exosome-like NTs from tea leaves (TLNTs), which had an average diameter of 166.9 nm and a negative-charged surface of - 28.8 mV. These TLNTs contained an adequate slew of functional components such as lipids, proteins and pharmacologically active molecules. In vitro studies indicated that TLNTs were effectively internalized by breast tumor cells (4T1 cells) and caused a 2.5-fold increase in the amount of intracellular reactive oxygen species (ROS) after incubation for 8 h. The high levels of ROS triggered mitochondrial damages and arrested cell cycles, resulting in the apoptosis of tumor cells. The mouse experiments revealed that TLNTs achieved good therapeutic effects against breast tumors regardless of intravenous injection and oral administration through direct pro-apoptosis and microbiota modulation. Strikingly, the intravenous injection of TLNTs, not oral administration, yielded obvious hepatorenal toxicity and immune activation. These findings collectively demonstrate that TLNTs can be developed as a promising oral therapeutic platform for the treatment of breast cancer.

Cactus polysaccharides enhance preservative effects of ultrasound treatment on fresh-cut potatoes.

The shelf life of fresh-cut fruits and vegetables is affected by microbial growth, enzymatic browning, and loss of flavor. Although ultrasound (US) treatment is often used in the preservation of fresh-cut fruits and vegetables, it has limited antibacterial and preservative effects. Here, we used cactus polysaccharides (CP) to enhance the preservative effect of ultrasound treatment and extended the shelf life of fresh-cut potatoes. The results showed that combined treatment (CP + US) exerted better antimicrobial and anti-browning effects than individual treatments (either US or CP alone). In addition, CP + US has no adverse effect on texture and quality properties, as well as reduced the mobility of internal water. Combination treatment not only significantly decreased the activities of polyphenol oxidase and peroxidase (P < 0.05), but also maintained a high level of phenylalanine ammonia lyase activity and total phenol content during storage. It also maintained the integrity of cell membrane and reduced its permeability by inhibiting the peroxidation of membrane lipids. In addition, CP + US treatment significantly inhibited the activity of antioxidant enzymes and maintained a high DPPH scavenging ability. GC-IMS technology was used to evaluate the flavor of fresh-cut potatoes. The results showed that CP + US treatment reduced the production of a peculiar smell during storage and maintained a good flavor by inhibiting the production of aldehydes. Taken together, these results indicate that the effective preservation method of CP + US treatment can be utilized to increase the shelf life of fresh-cut potatoes.

Phenformin suppresses angiogenesis through the regulation of exosomal microRNA-1246 and microRNA-205 levels derived from oral squamous cell carcinoma cells.

Exosomes secreted by cancer cells are important components in the tumor microenvironment, enabling cancer cells to communicate with each other and with noncancerous cells to play important roles in tumor progression and metastasis. Phenformin, a biguanide antidiabetic drug, has been reported to have a strong antitumor function in multiple types of cancer cells, however little research has been reported about whether phenformin can regulate the secretion of exosomes by cancer cells to regulate the tumor microenvironment and contribute to its antitumor function. Here we found that exosomes (Phen-Exo) derived from phenformin-treated oral squamous cell carcinoma (OSCC) cells significantly suppress the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. The inhibition of angiogenesis by Phen-Exo was verified in vivo by matrigel plug angiogenesis assays and by chick chorioallantoic membrane assays. Mechanistically, we discovered that the expression of microRNA-1246 (miR-1246) and microRNA-205 (miR-205) was significantly increased in exosomes secreted by OSCC cells treated with phenformin, while high expression levels of miR-1246 or miR-205 in vascular endothelial cells inhibited their angiogenic effects and decreased expression of the angiogenic factor VEGFA. In conclusion, these results reveal that phenformin can inhibit angiogenesis by regulating the levels of miR-1246 and miR-205 in exosomes secreted by OSCC cells, suggesting that phenformin has the potential to alter the tumor microenvironment to antagonize the growth of OSCCs, which provides a theoretical basis for developing new strategies to treat OSCCs in the future.

Oral Nanomotor-Enabled Mucus Traverse and Tumor Penetration for Targeted Chemo-Sono-Immunotherapy against Colon Cancer.

The therapeutic outcomes of oral nanomedicines against colon cancer are heavily compromised by their lack of specific penetration into the internal tumor, favorable anti-tumor activity, and activation of anti-tumor immunity. Herein, hydrogen peroxide (H2 O2 )/ultrasound (US)-driven mesoporous manganese oxide (MnOx )-based nanomotors are constructed by loading mitochondrial sonosensitizers into their mesoporous channels and orderly dual-functionalizing their surface with silk fibroin and chondroitin sulfate. The locomotory activities and tumor-targeting capacities of the resultant nanomotors (CS-ID@NMs) are greatly improved in the presence of H2 O2 and US irradiation, inducing efficient mucus-traversing and deep tumor penetration. The excess H2 O2 in the tumor microenvironment (TME) is decomposed into hydroxyl radicals and oxygen by an Mn2+ -mediated Fenton-like reaction, and the produced oxygen participates in sonodynamic therapy (SDT), yielding abundant singlet oxygen. The combined Mn2+ -mediated chemodynamic therapy and SDT cause effective ferropotosis of tumor cells and accelerate the release of tumor antigens. Importantly, animal experiments reveal that the treatment of combining oral hydrogel (chitosan/alginate)-embedding CS-ID@NMs and immune checkpoint inhibitors can simultaneously suppress the growth of primary and distal tumors through direct killing, reversion of immunosuppressive TME, and potentiation of systemic anti-tumor immunity, demonstrating that the CS-ID@NM-based platform is a robust oral system for synergistic treatment of colon cancer.

Effects and mechanism of natural phenolic acids/fatty acids on copigmentation of purple sweet potato anthocyanins.

Anthocyanins are attractive alternatives to colorants; however, their low color stability hinders practical application. Copigmentation can enhance both the color intensity and color stability of complexes. Herein, we report an investigation of copigmentation reactions between purple sweet potato anthocyanins (PSA1) and phenolic acids (tannic, ferulic, and caffeic acids) or fatty acids (tartaric and malic acids) at pH 3.5. The effects of the mole ratios of the copigment and the reaction temperature were examined. In addition, quantum mechanical computations were performed to investigate molecular interactions. The optimum PSA:copigment molar ratio was found to be 1:100. The strongest bathochromic and hyperchromic effects were observed for copigmentation with tannic acid (Tan), which might be attributable to the fact that its HOMO-LUMO energy gap was the smallest among the investigated copigments, and because it has a greater number of phenolic aromatic and groups to form more van der Waals and hydrogen bond interactions. However, the formation of the PSA-caffeic acid (Caf) complex was accompanied by the greatest drop in enthalpy (-33.18 kJ/mol) and entropy (-74.55 kJ/mol), and this was the most stable complex at 90 °C. Quantum mechanical calculations indicated that hydrogen bonds and van der Waals force interactions contributed to the color intensification effect of copigmentation. These findings represent an advancement in our understanding of the properties of PSA, expanding the application scope of this natural product.

Phenformin Down-Regulates c-Myc Expression to Suppress the Expression of Pro-Inflammatory Cytokines in Keratinocytes.

The treatment of many skin inflammation diseases, such as psoriasis and atopic dermatitis, is still a challenge and inflammation plays important roles in multiple stages of skin tumor development, including initiation, promotion and metastasis. Phenformin, a biguanide drug, has been shown to play a more efficient anti-tumor function than another well-known biguanide drug, metformin, which has been reported to control the expression of pro-inflammatory cytokines; however, little is known about the effects of phenformin on skin inflammation. This study used a mouse acute inflammation model, ex vivo skin organ cultures and in vitro human primary keratinocyte cultures to demonstrate that phenformin can suppress acute skin inflammatory responses induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in vivo and significantly suppresses the pro-inflammatory cytokines IL-1ß, IL-6 and IL-8 in human primary keratinocytes in vitro. The suppression of pro-inflammatory cytokine expression by phenformin was not directly through regulation of the MAPK or NF-κB pathways, but by controlling the expression of c-Myc in human keratinocytes. We demonstrated that the overexpression of c-Myc can induce pro-inflammatory cytokine expression and counteract the suppressive effect of phenformin on cytokine expression in keratinocytes. In contrast, the down-regulation of c-Myc produces effects similar to phenformin, both in cytokine expression by keratinocytes in vitro and in skin inflammation in vivo. Finally, we showed that phenformin, as an AMPK activator, down-regulates the expression of c-Myc through regulation of the AMPK/mTOR pathways. In summary, phenformin inhibits the expression of pro-inflammatory cytokines in keratinocytes through the down-regulation of c-Myc expression to play an anti-inflammation function in the skin.

Role of magnesium-doped calcium sulfate and ß-tricalcium phosphate composite ceramics in macrophage polarization and osteo-induction.

In the current study, we explored the role of Mg2+-doped CaSO4/ß-TCP composite biopolymer in regulating macrophage polarization and its relation with enhanced osteogenic differentiation of periodontal ligament stem cells. Furthermore, mechanism underling the regulation of macrophage polarization by CaSO4/ß-TCP was evaluated. Mg2+-doped CaSO4/ß-TCP composite was characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Macrophage polarization was characterized using flow cytometry analysis. Macrophage morphometric analysis was conducted by FITC phalloidin staining. Western blot and qRT-PCR assays were used to assess gene expression levels and miRNAs, respectively. SEM morphology of CaSO4/ß-TCP ceramic revealed a particle size of 10-50 µm, and XRD spectrum showed that characteristic peak of samples was consistent with that of CaSO4 and ß-TCP. Results from flow cytometry evidenced significant upregulation of M2 macrophage markers after adding ceramic biopolymer, indicating the induction of inactivated M0 macrophage polarization to M2 macrophage. Macrophage morphometric analysis revealed development of lamellar pseudopodia on day 7 in CaSO4/ß-TCP group. Furthermore, flow cytometry revealed high positivity rate of 90.34% (CD44) and 89.36% (CD146). qRT-PCR results showed that the level of miR-21-5p was significantly decreased in M2 macrophages. Moreover, western blot analysis revealed upregulated expression levels of RUNX2, osterix (Osx), and osteopontin (OPN), and ELISA exhibited increase in cytokine levels (IL-1ß, IL-10, TGF-ß1, and BMP-2) in the presence of macrophages, indicating the osteogenic differentiation ability of periodontal ligament stem cells. The study evidenced the regulation of macrophage polarization by Mg2+-doped CaSO4/ß-TCP composite ceramic and its mediation through lncRNA PVT1/miR-21-5p/smad2 molecular axis.

Near-Infrared-Enpowered Nanomotor-Mediated Targeted Chemotherapy and Mitochondrial Phototherapy to Boost Systematic Antitumor Immunity.

Phototherapy is an important strategy to inhibit tumor growth and activate antitumor immunity. However, the effect of photothermal/photodynamic therapy (PTT/PDT) is restricted by limited tumor penetration depth and unsatisfactory potentiation of antitumor immunity. Here, a near-infrared (NIR)-driven nanomotor is constructed with a mesoporous silicon nanoparticle (MSN) as the core, end-capped with Antheraea pernyi silk fibroin (ApSF) comprising arginine-glycine-aspartate (RGD) tripeptides. Upon NIR irradiation, the resulting ApSF-coated MSNs (DIMs) loading with photosensitizers (ICG derivatives, IDs) and chemotherapeutic drugs (doxorubicin, Dox) can efficiently penetrate into the internal tumor tissues and achieve effective phototherapy. Combined with chemotherapy, a triple-modal treatment (PTT, PDT, and chemotherapy) approach is developed to induce the immunogenic cell death of tumor cells and to accelerate the release of damage-associated molecular patterns. In vivo results suggest that DIMs can promote the maturation of dendritic cells and surge the number of infiltrated immune cells. Meanwhile, DIMs can polarize macrophages from M2 to M1 phenotypes and reduce the percentages of immunosuppressive Tregs, which reverse the immunosuppressive tumor microenvironment and activate systemic antitumor immunity. By achieving synergistic effects on the tumor inhibition and the antitumor immunity activation, DIMs show great promise as new nanoplatforms to treat metastatic breast cancer.

PSRR: A Web Server for Predicting the Regulation of miRNAs Expression by Small Molecules.

Background: MicroRNAs (miRNAs) play key roles in a variety of pathological processes by interacting with their specific target mRNAs for translation repression and may function as oncogenes (oncomiRs) or tumor suppressors (TSmiRs). Therefore, a web server that could predict the regulation relations between miRNAs and small molecules is expected to achieve implications for identifying potential therapeutic targets for anti-tumor drug development. Methods: Upon obtaining positive/known small molecule-miRNA regulation pairs from SM2miR, we generated a multitude of high-quality negative/unknown pairs by leveraging similarities between the small molecule structures. Using the pool of the positive and negative pairs, we created the Dataset1 and Dataset2 datasets specific to up-regulation and down-regulation pairs, respectively. Manifold machine learning algorithms were then employed to construct models of predicting up-regulation and down-regulation pairs on the training portion of pairs in Dataset1 and Dataset2, respectively. Prediction abilities of the resulting models were further examined by discovering potential small molecules to regulate oncogenic miRNAs identified from miRNA sequencing data of endometrial carcinoma samples. Results: The random forest algorithm outperformed four machine-learning algorithms by achieving the highest AUC values of 0.911 for the up-regulation model and 0.896 for the down-regulation model on the testing datasets. Moreover, the down-regulation and up-regulation models yielded the accuracy values of 0.91 and 0.90 on independent validation pairs, respectively. In a case study, our model showed highly-reliable results by confirming all top 10 predicted regulation pairs as experimentally validated pairs. Finally, our predicted binding affinities of oncogenic miRNAs and small molecules bore a close resemblance to the lowest binding energy profiles using molecular docking. Predictions of the final model are freely accessible through the PSRR web server at https://rnadrug.shinyapps.io/PSRR/. Conclusion: Our study provides a novel web server that could effectively predict the regulation of miRNAs expression by small molecules.

Edible plant-derived nanotherapeutics and nanocarriers: recent progress and future directions.

INTRODUCTION: High drug delivery efficiency, desirable therapeutic effects, and low toxicity have become crucial to develop nanotherapeutics. Natural nanoparticles (NPs) from edible plants contain a large quantity of bioactive small molecules, proteins, glycolipids, and microRNAs. The development of these NPs has rapidly attracted increasing attention due to their merits of green production, excellent biocompatibility, anti-inflammatory activities, and antitumor capacities. AREAS COVERED: Here, we introduce the extraction, purification, and construction strategies of plant-derived exosome-like NPs (PDENs) and expound on their physicochemical properties, biomedical functions, and therapeutic effects against various diseases. We also recapitulate future directions and challenges of the emerging nanotherapeutics. EXPERT OPINION: PDENs have been used as natural nanotherapeutics and nanocarriers. The challenges of applying PDENs primarily stem from the lack of understanding of the mechanisms that drive the tissue-specific targeting properties. Elucidating the underlying targeting mechanisms is one of the major focuses in this review, which helps to gain new research opportunities for the development of natural nanotherapeutics. Despite excellent biosafety and therapeutic effects in the treatment of various diseases, the medical translation of these NPs has still been limited by low yields and cold-chain dependence. Therefore, exploiting new techniques will be required for their massive production and storage.

Complex Age- and Cancer-Related Changes in Human Blood Transcriptome-Implications for Pan-Cancer Diagnostics.

Early cancer detection is the key to a positive clinical outcome. While a number of early diagnostics methods exist in clinics today, they tend to be invasive and limited to a few cancer types. Thus, a clear need exists for non-invasive diagnostics methods that can be used to detect the presence of cancer of any type. Liquid biopsy based on analysis of molecular components of peripheral blood has shown significant promise in such pan-cancer diagnostics; however, existing methods based on this approach require improvements, especially in sensitivity of early-stage cancer detection. The improvement would likely require diagnostics assays based on multiple different types of biomarkers and, thus, calls for identification of novel types of cancer-related biomarkers that can be used in liquid biopsy. Whole-blood transcriptome, especially its non-coding component, represents an obvious yet under-explored biomarker for pan-cancer detection. In this study, we show that whole transcriptome analysis using RNA-seq could indeed serve as a viable biomarker for pan-cancer detection. Furthermore, a class of long non-coding (lnc) RNAs, very long intergenic non-coding (vlinc) RNAs, demonstrated superior performance compared with protein-coding mRNAs. Finally, we show that age and presence of non-blood cancers change transcriptome in similar, yet not identical, directions and explore implications of this observation for pan-cancer diagnostics.