The Application of Nanoparticle-Based Imaging and Phototherapy for Female Reproductive Organs Diseases.

Various female reproductive disorders affect millions of women worldwide and bring many troubles to women's daily life. Let alone, gynecological cancer (such as ovarian cancer and cervical cancer) is a severe threat to most women's lives. Endometriosis, pelvic inflammatory disease, and other chronic diseases-induced pain have significantly harmed women's physical and mental health. Despite recent advances in the female reproductive field, the existing challenges are still enormous such as personalization of disease, difficulty in diagnosing early cancers, antibiotic resistance in infectious diseases, etc. To confront such challenges, nanoparticle-based imaging tools and phototherapies that offer minimally invasive detection and treatment of reproductive tract-associated pathologies are indispensable and innovative. Of late, several clinical trials have also been conducted using nanoparticles for the early detection of female reproductive tract infections and cancers, targeted drug delivery, and cellular therapeutics. However, these nanoparticle trials are still nascent due to the body's delicate and complex female reproductive system. The present review comprehensively focuses on emerging nanoparticle-based imaging and phototherapies applications, which hold enormous promise for improved early diagnosis and effective treatments of various female reproductive organ diseases.

Arginine Supplementation Targeting Tumor-Killing Immune Cells Reconstructs the Tumor Microenvironment and Enhances the Antitumor Immune Response.

The tumor microenvironment (TME) is characterized by several immunosuppressive factors, of which weak acidity and l-arginine (l-arg) deficiency are two common features. A weak acidic environment threatens the survival of immune cells, and insufficient l-arg will severely restrain the effect of antitumor immune responses, both of which affect the efficiency of cancer treatments (especially immunotherapy). Meanwhile, l-arg is essential for tumor progression. Thus, two strategies, l-arg supplementation and l-arg deprivation, are developed for cancer treatment. However, these strategies have the potential risk of promoting tumor growth and impairing immune responses, which might lead to a paradoxical therapeutic effect. It is optimal to limit the l-arg availability of tumor cells from the microenvironment while supplying l-arg for immune cells. In this study, we designed a multivesicular liposome technology to continuously supply alkaline l-arg, which simultaneously changed the acidity and l-arg deficiency in the TME, and by selectively knocking down the CAT-2 transporter, l-arg starvation of tumors was maintained while tumor-killing immune cells were enriched in the TME. The results showed that our strategy promoted the infiltration and activation of CD8+ T cells in tumor, increased the proportion of M1 macrophages, inhibited melanoma growth, and prolonged survival. In combination with anti-PD-1 antibody, our strategy reversed the low tumor response to immune checkpoint blockade therapy, showing a synergistic antitumor effect. Our work provided a reference for improving the TME combined with regulating nutritional competitiveness to achieve the sensitization of immunotherapy.

Lingguizhugan decoction protects PC12 cells against Aß25-35-induced oxidative stress and neuroinflammation by modulating NF-κB/MAPK signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is recognized as one of the most prevalent neurodegenerative diseases. Lingguizhugan decoction (LGZGD) is a classical traditional Chinese medicine (TCM). Many studies have shown that LGZGD can alleviate the symptoms of AD. AIM OF THE STUDY: The aim of this study was to assess the neuroprotective effects of LGZGD and elucidate its molecular mechanism on Aß25-35-induced PC12 cells. MATERIALS AND METHODS: PC12 cells were used MTT assays, ELISA, fluorescence probe analyses, Hoechst 33342 staining, immunofluorescent staining and western blot analyses were systematically conducted to evaluate the underlying mechanisms of LGZGD. RESULTS: In Aß25-35-induced PC12 cells, LGZGD remarkably increased cell viability, reduced the generation of TNF-α, IL-1ß, IL-6, MDA and ROS, increased the activity of GSH-Px, inhibited cell apoptosis, downregulated the expression of Bax and cleaved caspase-3, and upregulated the expression of Bcl-2. Moreover, LGZGD modulated the NF-κB/MAPK signaling pathways by upregulating the levels of IκBα and phospho-ERK, while downregulating the levels of phospho-p65, phospho-IκBα, and phospho-p38. Furthermore, LGZGD repressed the nuclear translocation activity of NF-κB p65. Meanwhile, LGZGD increased the expression of phospho-GSK-3ß and reversed the hyperphosphorylation of Tau proteins by inhibiting the activation of the ERK MAPK pathway. CONCLUSIONS: Taken together, the present study suggested that LGZGD may be a valuable drug candidate that can attenuate the neurotoxicity induced by Aß25-35 by modulating the NF-κB/MAPK signaling pathways in PC12 cells.

Qualitative and quantitative analysis of Alpiniae Oxyphyllae Fructus by high-performance liquid chromatography coupled to Fourier transform-ion cyclotron resonance mass spectrometry.

Alpiniae Oxyphyllae Fructus, as a homology of medicine and food, has been widely used in China for thousands of years. However, the existing qualitative and quantitative methods are difficult to evaluate the quality of Alpiniae Oxyphyllae Fructus samples from multiple sources. In this paper, an high-performance liquid chromatography fingerprint was established for assessing the quality of Alpiniae Oxyphyllae Fructus from different areas. Then, high-performance liquid chromatography was coupled to Fourier transform-ion cyclotron resonance mass spectrometry for characterization of the chemical compositions in Alpiniae Oxyphyllae Fructus. In fingerprint analysis, 54 common peaks were confirmed and six chromatographic peaks of them were identified. The similarity of 14 samples from different areas was between 0.990 and 1.000. Moreover, a total of 30 chemical components were characterized by high-performance liquid chromatography coupled to Fourier transform-ion cyclotron resonance mass spectrometry method, six compounds of which were decisively identified. Finally, the content of nootkatone was determined by high-performance liquid chromatography. In conclusion, the methods used in this study are efficient for qualitative and quantitative analysis of Alpiniae Oxyphyllae Fructus. Also, these methods can be used to control the quality of other traditional Chinese medicines.

Studies on chemical constituents of Flos Puerariae-Semen Hoveniae medicine pair by HPLC and Fourier transform ion cyclotron resonance mass spectrometry.

Alcoholic liver disease is currently the most clinically concerning liver disease, which occurs from chronic alcohol abuse. Flos Puerariae and Semen Hoveniae have been used to treat alcohol drinking excessively for thousands of years in China. In this study, the ethanol extract of the medicine pair was qualitatively and quantitatively analyzed by high-performance liquid chromatography and Fourier transform ion cyclotron resonance mass spectrometry. First, the high-performance liquid chromatography fingerprint was established to obtain the overall chromatographic data of its chemical constituents. Next, high-performance liquid chromatography-mass spectrometry was applied to identify its chemical constituents. Then, the characteristic constituents were simultaneously quantified by high-performance liquid chromatography. In addition, the chemical constituents that were absorbed into rat plasma were identified by high-performance liquid chromatography-mass spectrometry. As a result, a total of 48 chemical constituents in the medicine pair were detected and identified in vitro. Meanwhile, the content of seven representative constituents, including dihydromyricetin, glycitin, genistin, tectoridin, glycitein, genistein, and tectorigenin were simultaneously determined. Furthermore, a total of 19 chemical constituents were detected in rat plasma after oral administration. In short, the chemical constituents of the medicine pair were initially investigated in this study, which will lay the foundation for the discovery of its pharmacodynamic substances in further works.

Quality control of Semen Hoveniae by high-performance liquid chromatography coupled to Fourier transform-ion cyclotron resonance mass spectrometry.

A method based on high-performance liquid chromatography and Fourier transform-ion cyclotron resonance mass spectrometry was developed to control the quality of Semen Hoveniae. First, the chromatographic fingerprint was established in combination with the chemometrics methods such as similarity analysis, cluster analysis, principal component analysis, and orthogonal partial least squares discriminant analysis to discover the qualitative markers. Then, an high-performance liquid chromatography mass spectrometry method was developed to identify the chemical constituents in Semen Hoveniae. Moreover, the content of dihydromyricetin and dihydroquercetin in Semen Hoveniae were determined by high-performance liquid chromatography. As a result, nine common peaks were assigned in the fingerprints and the similarity of the 13 batch samples varied from 0.425 to 0.993, indicating an obviously different quality. Dihydromyricetin and dihydroquercetin were the main qualitative markers to differ the quality of Semen Hoveniae. Meanwhile, a total of 21 chemical compounds were characterized by high-performance liquid chromatography mass spectrometry and six of them were identified by comparing with information of reference standards. Finally, the content of dihydromyricetin and dihydroquercetin in 13 batch samples varied from 0.824  to 7.499 mg/g and from 0.05941  to 4.258 mg/g , respectively. In conclusion, the methods developed here will provide sufficient qualitative and quantitative information for the quality control of Semen Hoveniae.

Recent Progress in the Development of Multifunctional Nanoplatform for Precise Tumor Phototherapy.

Phototherapy, including photodynamic therapy and photothermal therapy, mainly relies on phototherapeutic agents (PAs) to produce heat or toxic reactive oxygen species (ROS) to kill tumors. It has attracted wide attention due to its merits of noninvasive properties and negligible drug resistance. However, the phototoxicity of conventional PAs is one of the main challenges for its potential clinical application. This is mainly caused by the uncontrolled distribution of PA in vivo, as well as the inevitable damage to healthy cells along the light path. Ensuring the generation of ROS or heat specific at tumor site is the key for precise tumor phototherapy. In this review, the progress of targeted delivery of PA and activatable phototherapy strategies based on nanocarriers for precise tumor therapy is summarized. The research progress of passive targeting, active targeting, and activatable targeting strategies in the delivery of PA is also described. Then, the switchable nanosystems for tumor precise phototherapy in response to tumor microenvironment, including pH, glutathione (GSH), protein, and nucleic acid, are highlighted. Finally, the challenges and opportunities of nanocarrier-based precise phototherapy are discussed for clinical application in the future.

Polydatin alleviates parkinsonism in MPTP-model mice by enhancing glycolysis in dopaminergic neurons.

Parkinson's disease (PD) is a common neurodegenerative disease. Damage to energy metabolism and reduced adenosine triphosphate (ATP) levels in dopaminergic neurons are common features of PD. Previous studies suggested that the occurrence of PD often affects glucose metabolism and ATP production in the brain, and increased glycolysis or ATP production protects dopaminergic neuronal degeneration in the brain of PD patients. These systems may provide new potential therapeutic targets for the prevention of PD. The present study investigated the inhibitory action of polydatin (PLD) on early dopaminergic neuronal degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results showed that PLD protected against MPTP-induced early dopaminergic neuronal degeneration. PLD reduced the MPTP-induced loss of dopaminergic neurons in substantia nigra and striatum, inhibited the occurrence of neural apoptosis, and restored motor function in mice. PLD also increased the continuous activity duration and rhythm amplitude in mice during the circadian activity test. PLD improved glucose metabolism in the brain and restored ATP production levels. These observations suggest that PLD attenuates MPTP-induced early PD-like symptoms, and its mechanism of action may be associated with the promotion of glucose metabolism in neurons.

Enhancing the hardness of potato slices after boiling by combined treatment with lactic acid and calcium chloride: Mechanism and optimization.

Potatoes usually suffer from greatly decrease of hardness after boiling, which limits their processing potential in food industry. Moreover, methods for enhancing the hardness of potatoes after boiling are underexplored. In this study, the hardness of potato slices after boiling were increased from 288 g to 2342 g by the combined treatment of lactic acid (LA) and calcium chloride (CC). Through the analysis of the microstructure of the potato cells, the molecular weight distribution and natural sugar ratio of different soluble pectin fractions, and the enzymatic activities (polygalacturonase, PG and pectin methylesterase, PME), the possible mechanism behind the hardness enhancement by LA and CC pretreatment, namely the direct link between pectin and potato structure was revealed. The obtained results confirmed the target spot for enhancing the hardness of potatoes after boiling lay in PG activity and gelation of the pectin, which also could be used to help other plants resist the heat process if pectin existed in their cell wall.

Drug Repurposing Screen Identifies Novel Classes of Drugs with Anticancer Activity in Mantle Cell Lymphoma.

AIM AND OBJECTIVE: Mantle Cell Lymphoma (MCL) is typically an aggressive and rare disease with poor prognosis, therefore new effective therapeutics are urgently needed. Drug repurposing for cancer treatment is becoming increasingly more attractive as an alternative approach to discover clinically approved drugs that demonstrate antineoplastic effect. The objective of this study was to screen an approved drug library and identify candidate compounds with an antineoplastic effect in MCL cells using High-Throughput Screening (HTS) technique. MATERIALS AND METHODS: Using the HTS technique, nearly 3,800 clinically approved drugs and drug candidates were screened in Jeko and Mino MCL cell lines. We also demonstrated the selectivity window of the candidate compounds in six normal cell lines. Further validations were performed in caspase-3/7 apoptosis assay and three-dimensional (3D) multicellular aggregates model using Z138 cell line. RESULTS: We identified 98 compounds showing >50% inhibition in either MCL cell line screened, they were distributed across eight unique therapeutic categories and have different mechanisms of action (MOA). We selected alisertib, carfilzomib, pracinostat and YM155 for further validation based on their antiproliferative activity in two MCL cell lines, selectivity to normal cell lines, and drug developing stages in terms of clinical research. Alisertib and carfilzomib showed antiproliferative effect on MCL cell with EC50 = 6 nM and >100-fold selectivity to normal cell lines, especially for alisertib which demonstrated >1000-fold selectivity to 5 out of 6 normal cell lines. Pracinostat and YM155 had potency of 11 and 12 nM in MCL cell with >20-fold selectivity to normal cell lines. All four compounds had been tested in caspase-dependent apoptosis assay. We further validated and demonstrated their anti-MCL effect on cell proliferation and (3D) multicellular aggregates model using Z138 cell line. CONCLUSION: This is the first study to examine such a large library of clinically approved compounds for the identification of novel drug candidates for MCL treatment, the results could be rapidly translated into clinical practice in patients with MCL.