Application of dual chemotherapeutic drug delivery system based on metal-organic framework platform in enhancing tumor regression for breast cancer research.

The nanomedicine system based on dual drug delivery systems (DDDs) can significantly enhance the efficacy of tumor treatment. Herein, a metal-organic framework, Zeolite imidazole salt frames 8 (ZIF-8), was successfully utilized as a carrier to load the dual chemotherapeutic drugs doxorubicin (DOX) and camptothecin (CPT), named DOX/CPT@ZIF-8 (denoted as DCZ), and their inhibitory effects on 4T1 breast cancer cells were evaluated. The study experimentally demonstrated the synergistic effects of the dual chemotherapeutic drugs within the ZIF-8 carrier and showed that the ZIF-8 nano-carrier loaded with the dual drugs exhibited stronger cytotoxicity and inhibitory effects on 4T1 breast cancer cells compared to single-drug treatment. The use of a ZIF-8-based dual chemotherapeutic drug carrier system highlighted its potential advantages in suppressing 4T1 breast cancer cells.

Reproductive Toxicity Evaluation of Graphene-Based Tumor Cell Nucleus-Targeting Fluorescent Nanoprobes on Reproduction and Offspring Health.

A new graphene-based fluorescent nanoprobe for tumor cell nucleus (GTTNs) was synthesized in our laboratory that penetrates the cell membrane and particularly targets cancer cell nucleus and displays tremendous potential for clinical applications. Although acute and subacute toxicity studies have been conducted on GTTNs, a primary result could be drawn that GTTNs appear to have almost no acute and subacute toxicity. However, as an important part of safety evaluation, the influences on reproductive and offspring developmental toxicity are still absent. In this study, male mice were injected intravenously with GTTNs, and the survival status, histopathology of the testes and epididymides, proliferation and apoptosis of testicular tissue, and sperm motility of mice were measured. To evaluate the short- and long-term fertility in male mice, different male mice resided with untreated female mice on days 1 and 30 after the end of the last treatment, and the offspring health parameters were assessed by measuring pup numbers, body weight, and organ indexes of the pups. The results indicated that GTTNs-exposed male mice retained good fertility, healthy structure of testes and epididymides, and production of healthy sperm. Meanwhile, there were no significant differences between the offspring and the control group. In consideration of GTTNs with broad prospects for biomedical applications, our results contribute a basis for further understanding of its biosafety.

Acute and Subacute Toxicity Study of Graphene-Based Tumor Cell Nucleus-Targeting Fluorescent Nanoprobes.

Graphene-based tumor cell nuclear targeting fluorescent nanoprobes (GTTNs) were synthesized in our laboratory as a kind of nanomaterial and showed good performance for both in vivo and in vitro imaging. GTTNs directly cross the cell membrane and specifically target the tumor cell nucleus via a cell membrane permeability targeting (CMPT) mechanism, which takes advantage of the increased permeability of the tumor cell membranes. GTTNs with a CMPT mechanism achieve high targeting efficiency in tumor tissues. With the tumor cell nucleus-targeting characterization, the GTTN distinguishes tumor cells at the single-cell level and recognizes the tumor tissue interface in a very early stage and shows great potential in clinical applications. Toxicity studies are extremely critical for clinical applications. Therefore, we studied the acute and subacute toxicity of GTTNs using an in vivo method and examined the following experimental indicators: mouse body weight, organ coefficients, serum biochemical parameters, and histological changes. The results showed that there were no significant differences in any indicators between the experimental and control mice. We also used an in vitro method to study the cytotoxicity of GTTNs in GES-1 (gastric epithelial cell) cells. Surprisingly, the results demonstrated over 80% cell viability when the incubation time reached up to 72 h under a 200 mg/L concentration of GTTNs, which indicated that GTTNs had low cytotoxicity. GTTNs barely showed any acute or subacute toxicity or cytotoxicity in vivo and in vitro, respectively, which supports their use for clinical applications.

Enzymatic Preparation, In-Depth Molecular Analysis, and In Vitro Digestion Simulation of Palmitoleic Acid (ω-7)-Enriched Fish Oil Triacylglycerols.

In this study, an enzymatic reaction was developed for synthesizing pure triacylglycerols (TAG) with a high content of palmitoleic acid (POA) using fish byproduct oil. The characteristics of synthesized structural TAGs rich in POA (POA-TAG) were analyzed in detail through ultrahigh-performance liquid chromatography Q Exactive orbitrap mass spectrometry. Optimal conditions were thoroughly investigated and determined for reaction systems, including the use of Lipozyme TL IM and Novozym 435, 15 wt % lipase loading, substrate mass ratio of 1:3, and water content of 2.5 and 0.5 wt %, respectively, resulting in yields of 67.50 and 67.45% for POA-TAG, respectively. Multivariate statistical analysis revealed that TAG 16:1/16:1/20:4, TAG 16:1/16:1/16:1, TAG 16:1/16:1/18:1, and TAG 16:0/16:1/18:1 were the main variables in Lipozyme TL IM and Novozym 435 enzyme-catalyzed products under different water content conditions. Finally, the fate of POA-TAG across the gastrointestinal tract was simulated using an in vitro digestion model. The results showed that the maximum release of free fatty acids and apparent rate constants were 71.44% and 0.0347 s-1, respectively, for POA-TAG lipids, and the physical and structural characteristics during digestion depended on their microenvironments. These findings provide a theoretical basis for studying the rational design of POA-structural lipids and exploring the nutritional and functional benefits of POA products.

Evaluation of Lipid Oxidation Characteristics in Salmon after Simulation of Cold Chain Interruption Using Rapid Evaporation Ionization Mass Spectrometry.

Temperature fluctuations occurring during the cold chain logistics of salmon contribute to lipid oxidation. This study aimed to simulate cold chain interruption through freeze-thaw operations and evaluate the lipidomics data from salmon samples subjected to different numbers of freeze-thaw cycles by using rapid evaporative ionization mass spectrometry (REIMS) combined with an intelligent surgical knife (iKnife). The results indicated significant differences in the relative abundance of characteristic ions among the samples (p < 0.05). A total of 34 ions with variable importance for the projection values ≥1 were identified as potential biomarkers, including m/z 719.4233 ([PCC36:5-NH(CH3)3]-), m/z 337.3134 ([FAC22:1]-), m/z 720.4666 ([PEC35:6-H]-), m/z 309.2780 ([FAC20:1]-), m/z 777.4985 ([PCC40:4-NH(CH3)3]-), m/z 745.4421 ([PCC38:6-NH(CH3)3]-/[PEC38:6-NH3]-), m/z 747.4665 ([PCC38:5-NH(CH3)3]-/[PEC38:5-NH3]-), etc. The degree of lipid oxidation was found to be associated with the number of freeze-thaw cycles, exhibiting the most significant alterations in the relative abundance of lipid ions in the 8T samples. Additionally, sensory evaluation by the CIE-L*a*b* method and volatile analysis by headspace solid-phase microextraction gas chromatography-mass spectrometry demonstrated significant differences (p < 0.05) in color and odor among the salmon samples, with a correlation to the number of freeze-thaw cycles. The primary compounds responsible for alterations in salmon odor were aldehydes with lower odor thresholds. In summary, the iKnife-REIMS method accurately differentiated salmon muscle tissues based on varying levels of lipid oxidation, thus expanding the application of REIMS.

Changes in diet, exercise and psychology of the quarantined population during the COVID-19 outbreak in Shanghai.

BACKGROUND: In March 2022, a severe outbreak of COVID-19 broke out in Shanghai, with the virus spreading rapidly. In the most severe two months, more than 50,000 people were diagnosed with COVID-19. For this reason, Shanghai adopted three-district hierarchical management, requiring corresponding people to stay at home to contain the spread of the virus. Due to the requirements of prevention and control management, the diet, exercise and mental health of the corresponding population are affected to a certain extent. OBJECTIVES: This article aimed to understand the population in the diet, exercise and psychological changes. METHODS: This study carried out the research by distributing the electronic questionnaire and carried out the statistical analysis. RESULTS: People reduced the intake of vegetables and fruits (P = 0.000<0.05), people did about an hour less exercise per week on average (P = 0.000<0.05), the number of steps they took per day decreased by nearly 2000 steps (P = 0.012<0.05), and there were significant changes in the way they exercised. CONCLUSION: In terms of psychological state, people have some depression, anxiety and easy to feel tired after lockdown. This study can also provide reference for policy adjustment and formulation of normalized epidemic management in the future.

Machine learning-guided REIMS pattern recognition of non-dairy cream, milk fat cream and whipping cream for fraudulence identification.

The illegal adulteration of non-dairy cream in milk fat cream during the manufacturing process of baked goods has significantly hindered the robust growth of the dairy industry. In this study, a method based on rapid evaporative ionization mass spectrometry (REIMS) lipidomics pattern recognition integrated with machine learning algorithms was established. A total of 26 ions with importance were picked using multivariate statistical analysis as salient contributing features to distinguish between milk fat cream and non-dairy cream. Furthermore, employing discriminant analysis, decision trees, support vector machines, and neural network classifiers, machine learning models were utilized to classify non-dairy cream, milk fat cream, and minute quantities of non-dairy cream adulterated in milk fat cream. These approaches were enhanced through hyperparameter optimization and feature engineering, yielding accuracy rates at 98.4-99.6%. This artificial intelligent method of machine learning-guided REIMS pattern recognition can accurately identify adulteration of whipped cream and might help combat food fraud.

Polydopamine-guarded metal-organic frameworks as co-delivery systems for starvation-assisted chemo-photothermal therapy.

Cutting off glucose provision by glucose oxidase (GOx) to famish tumors can be an assistance with chemotherapy to eliminate cancer cells. Co-encapsulation of GOx and chemotherapeutics (doxorubicin) within pH-sensitive metal-organic frameworks (MOFs) could disorder metabolic pathways of cancer cells and generate excessive intracellular reactive oxygen species (ROS), together. To prevent premature leach of GOx from the porous channels of MOFs, polydopamine (PDA) was deposited on the surface of MOFs, which endowed the delivery system with photothermal conversion ability. Our nanoscaled co-delivery system (denoted as DGZPNs) remains stable with low amount of drug leakage under simulated physiological conditions in vitro and internal environment, while they are triggered to release doxorubicin (DOX) and GOx in acid tumor microenvironment and at high temperature for reinforced chemotherapy. NIR laser irradiation also activates superior photothermal conversion efficiency of PDA (36.9 %) to initiate hyperthermia to ablate tumor tissue. After being phagocytized by 4 T1 cells (breast cancer cells), the DGZPNs delivery system showed a superior therapeutic efficacy with a tumor growth inhibition of 88.9 ± 6.6 % under NIR irradiation, which indicated that the starvation-assisted chemo-photothermal therapy prompts the significant advance of synergistic therapy in a parallelly controlled mode.

[Open reduction and internal fixation with plate via posteromedial approach of retaining pes anserinus tendon in the treatment of tibial plateau fracture].

OBJECTIVE: To compare the effects of cutting and retaining the pes anserinus tendon on effectiveness following tibial plateau fracture. METHODS: A clinical data of 40 patients with tibial plateau fracture treated with open reduction and internal fixation with plate via posteromedial approach between January 2015 and January 2020 was retrospectively analyzed, including 18 patients retained the pes anserinus tendon (study group) and 22 patients cut the pes anserinus tendon (control group) during operation. There was no significant difference in gender, age, side of affected knee, cause of injury, Schatzker classification, time from injury to operation, and associated ligament injury between the two groups ( P>0.05). The operation time, intraoperative blood loss, hospital stay, anatomic reduction rate, incidence of complications, fracture healing time, knee flexion and extension range of motion at 2 weeks and 12 months, and knee extension range of motion at 3 months after operation were recorded and compared between the two groups. The visual analogue scale (VAS) score was used to evaluate the early postoperative pain improvement at 1, 3, and 14 days after operation and hospital for special surgery (HSS) score was used to evaluate the improvement of knee function at 3, 6, and 12 months after operation. RESULTS: The patients in both groups were followed up 12-15 months with an average of 12.8 months. There was no significant difference in operation time, intraoperative blood loss, and fracture healing time between the two groups ( P>0.05). The hospital stay in the control group was significantly longer than that in the study group ( t=8.339, P=0.000). There was no significant difference in the anatomic reduction rate (90.9% vs. 83.3%) between the control group and the study group ( χ 2=0.058, P=0.810). There were 1 case of proximal tibial osteomyelitis, 3 cases of skin necrosis, 3 cases of traumatic arthritis, and 2 cases of lower deep venous thrombosis after operation in the control group, and 1 case of metaphyseal nonunion, 2 cases of traumatic arthritis, and 1 case of lower deep venous thrombosis in the study group, showing no significant difference in the incidence of complications (40.9% vs. 22.2%) between the two groups ( χ 2=1.576, P=0.209). In the study group, knee flexion and extension range of motion at 2 weeks and 12 months and knee extension range of motion at 3 months after operation were significantly better than those of the control group ( P<0.05). VAS scores and HSS scores in both groups improved with time after operation ( P<0.05), in addition, the HSS score and VAS score of the study group were significantly better than those of the control group ( P<0.05). CONCLUSION: Compared with traditional pes anserinus tendon cutting group, pes anserinus tendon retaining group can significantly reduce postoperative short-term pain, improve postoperative knee range of motion and knee function within 1 year after operation.

A Multifunctional Photoacoustic/Fluorescence Dual-Mode-Imaging Gold-Based Theranostic Nanoformulation without External Laser Limitations.

Theranostics is a new type of biomedical technology that organically combines the diagnosis and therapy of diseases. Among molecular imaging techniques, the integration of photoacoustic (PA) and fluorescence (FL) imaging modes with high sensitivity and imaging depth provides precise diagnostic outcomes. Gold nanorods (Au NRs) are well-known contrast agents for PA imaging and photothermal therapy. However, their high toxicity, poor biocompatibility, rapid clearance, and the need for an external laser source limit their application. Therefore, modification of Au NRs with carbon-based nanomaterials (CBNs) is done to obtain a multifunctional dual-mode gold-based nanoformulation (mdGC), which preforms dual-mode imaging of PA and FL. The results show that mdGC promotes tumor cell apoptosis and exhibits good antitumor performance through the mitochondria-mediated apoptotic pathway by increasing the production of intracellular reactive oxygen species, reducing mitochondrial membrane potential, and regulating the expression of apoptosis-related genes. The targeting rate of mdGC to tumor tissue is up to 20.71 ± 1.94% ID g-1 ; the tumor growth inhibition rate is as high as 80.44% without external laser sources. In general, mdGC is a potential multifunctional diagnostic and therapy integrated nanoformulation.

Inhibition of cancer cell growth in cisplatin-resistant human oral cancer cells by withaferin-A is mediated via both apoptosis and autophagic cell death, endogenous ROS production, G2/M phase cell cycle arrest and by targeting MAPK/RAS/RAF signalling pathway.

The Editors of JBUON issue an Expression of Concern to 'Inhibition of cancer cell growth in cisplatin-resistant human oral cancer cells by withaferin-A is mediated via both apoptosis and autophagic cell death, endogenous ROS production, G2/M phase cell cycle arrest and by targeting MAPK/RAS/RAF signalling pathway', by Xuelian Yin, Guang Yang, Dongjie Ma, Zhejun Su, JBUON 2020;25(1):332-337; PMID: 32277651. Following the publication of the above article, readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

MicroRNA-221 Promotes Cell Proliferation and Inhibits Apoptosis in Osteosarcoma Cells by Directly Targeting FBXW11 and Regulating Wnt Signaling.

BACKGROUND AND OBJECTIVES: MicroRNAs play a crucial role in the progression of various cancers, and microRNA-221 (miR-221) has been observed to be significantly overexpressed in osteosarcoma (OS) cells. FBXW11, a vital F-box protein of the ubiquitin-proteasome system, mediates the proliferation and survival of cancer cells by targeting multiple substrates for degradation. FBXW11 inhibits OS growth and metastasis by antagonizing the ß-catenin/Wnt signaling pathway. Therefore, we hypothesized that miR-221 targets FBXW11 to mediate Wnt signaling and promote OS proliferation. METHODS: In this study, we demonstrated the increased expression of miR-221 and FBXW11 in OS tissues and cell lines by real-time polymerase chain reaction (RT-PCR). Moreover, to elucidate the regulatory mechanism(s) of miR-221 and FBXW11 in progression, cell viability and apoptosis were analyzed by the MTT assay and flow cytometry, respectively. RESULTS: The results showed that the overexpression of miR-221 in OS cells dramatically promoted cell growth and cell cycle progression, and inhibited apoptosis, whereas miR-221 inhibitors conversely inhibited proliferation and promoted apoptosis in OS cells. The data also showed that FBXW11 directly targeted miR-221 and miR-221 regulated OS cell proliferation and apoptosis by binding to FBXW11. We further confirmed that miR-221 targeted FBXW11 to promote proliferation and inhibit apoptosis in OS cell lines by inhibiting Wnt signaling. INTERPRETATION AND CONCLUSIONS: Overall, our study revealed a functional mechanism for miR-221 in OS. Further studies will elucidate its role in the progression of OS and inhibiting miR-221 may represent a useful treatment strategy.

An Efficient Carbon-Based Drug Delivery System for Cancer Therapy through the Nucleus Targeting and Mitochondria Mediated Apoptotic Pathway.

The emergence of nanocarriers solves the problems of antitumor drugs such as non-targeting, huge side effects, etc., and has been widely used in tumor therapy. Some kinds of antitumor drugs such as doxorubicin (DOX) mainly act on the nucleic acid causing DNA damage, interfering with transcription, and thereby disrupting or blocking the process of cancer cell replication. Herein, a new nanodrug delivery system, the carbon-based nanomaterials (CBNs)-Pluronic F127-DOX (CPD), is designed by using CBNs as a nanocarrier for DOX. As a result, the tumor growth inhibition rate of CPD group is as high as 79.42 ± 2.83%, and greatly reduces the side effects. The targeting rate of the CPD group of DOX in the tumor nucleus is 36.78%, and the %ID/g in tumor tissue is 30.09%. The CPD regulates the expression levels of Caspase-3, p53, and Bcl-2 genes by increasing intracellular reactive oxygen species (ROS) levels and reducing mitochondrial membrane potential, which indicates that mitochondrial-mediated pathways are involved in apoptosis. The CPD nanodrug delivery system increases the effective accumulation of DOX in tumor cell nuclei and tumor tissues, and generates massive ROS, thereby inhibiting tumor growth in vivo, representing a promising agent for anticancer applications.

Orchestration of biomimetic membrane coating and nanotherapeutics in personalized anticancer therapy.

Nanoparticle-based therapeutic and detectable modalities can augment anticancer efficiency, holding potential in capable target and suppressive metastases post administration. However, the individual discrepancies of the current "one-size-fits-all" strategies for anticancer nanotherapeutics have heralded the need for "personalized therapy". Benefiting from the special inherency of various cells, diverse cell membrane-coated nanoparticles (CMCNs) were established on a patient-by-patient basis, which would facilitate the personalized treatment of individual cancer patients. CMCNs in a complex microenvironment can evade the immune system and target homologous tumors with a suppressed immune response, as well as a prolonged circulation time, consequently increasing the drug accumulation at the tumor site and anticancer therapeutic efficacy. This review focuses on the emerging strategies and advances of CMCNs to synergistically integrate the merit of source cells with nanoparticulate delivery systems for the orchestration of personalized anticancer nanotherapeutics, thus discussing their rationalities in facilitating chemotherapy, imaging, immunotherapy, phototherapy, radiotherapy, sonodynamic, magnetocaloric, chemodynamic and gene therapy. Furthermore, the mechanism, challenges and opportunities of CMCNs in personalized anticancer therapy were highlighted to further boost cooperation from different fields, including materials science, chemistry, medicine, pharmacy and biology for the lab-to-clinic translation of CMCNs combined with the individual advantages of source cells and nanotherapeutics.

Insights into the binding mechanism of two-dimensional black phosphorus nanosheets-protein associations.

Exploring the protein-nanomaterials interactions is the topic of high relevance for the future applications of new nanomaterials in biological system. Herein, the binding mechanism of bovine serum albumin(BSA) and bovine hemoglobin(BHB) with two-dimensional black phosphorus nanosheets (BP NSs) was reported. Muti-spectral results showed that the combination of BP NPs with protein resulted in the fluorescence quenching of BSA and BHB and induced the extension of the protein peptide chain by van der Waals forces, hydrophobic forces, and electron-transfer forces. Both BSA and BHB retain their structure in α-helix form. The induced circular dichroism (ICD) spectral results showed that the presence of BP NPs partly destroyed the binding domain of BHB with bilirubin and altered the tertiary structure of BHB by BP NPs binding.

Inhibition of cancer cell growth in cisplatin-resistant human oral cancer cells by withaferin-A is mediated via both apoptosis and autophagic cell death, endogenous ROS production, G2/M phase cell cycle arrest and by targeting MAPK/RAS/RAF signalling pathway.

PURPOSE: Oral cancer is one of the common oral cavity and pharynx cancers and its treatment is limited by early metastasis, late diagnosis and emergence of drug resistance. Herein we investigated the anticancer effects of Withaferin-A against the cisplatin-resistant SCC-4 human oral cancer cells. METHODS: The proliferation rate of the human oral cancer cells was evaluated by CCK-8 assay. Apoptotic cell death was studied by acridine orange (AO) / ethidium bromide (EB) staining as well as by flow cytometry using annexin V/propidium iodide (PI) staining. Cell cycle analysis was performed by flow cytometry. Reactive oxygen species (ROS) examination was carried out by flow cytometry. Protein expressions were determined by immunoblotting. RESULTS: The results of the MTT assay showed that Withaferin-A caused decrease in the proliferation of SCC-4 cells and exhibited an IC50 of 14 µM. The anticancer effects of Withaferin-A were mainly due to the induction of apoptosis which was linked with upsurge of Bax and depletion of BCl-2. Annexin V/PI assay showed that the apoptotic cells were 0.75, 5.8, 12.4 and 22.66% at 0,7,14 and 28 µM concentrations of Withaferin-A. Withaferin-A also caused increase in the ROS and decrease in the MMP levels of the SCC-4 cells. Western blot analysis showed that the expression of LC3B II increased while of p62 decreased remarkably upon treatment with Withaferin-A, suggestive of autophagic cell death. Cell cycle analysis by flow cytometry showed that Withaferin-A caused increase in the G2/M phase cells triggering arrest of cancer cells at the G2/M checkpoint of the cell cycle. Finally, western blot analysis showed that Withaferin-A blocked the MAPK/RAS/RAF signalling pathway in the SCC-4 cells. CONCLUSIONS: These results suggest that Withaferin-A may prove a potent lead molecule in oral cancer treatment and warrants further investigations.

Anticancer activity of Phloretin against the human oral cancer cells is due to G0/G1 cell cycle arrest and ROS mediated cell death.

PURPOSE: Phloretin is one of the important polyphenolics abundantly present across the plant kingdom. Studies have reported the anticancer effects of Phloretin against different human cancer cells. Nonetheless, the anticancer effects of Phloretin have not been explored against the human oral cancer cells. Therefore this study was designed to investigate the anticancer effects of Phloretin against the human oral cancer cells. METHODS: CCK-8 assay was used for the determination of cell viability. Annexin V/propidium iodide (PI) staining and flow cytometry were used for necrosis detection and cell cycle analysis, respectively. Wound healing assay was used for cell migration analysis. Western blot analysis was used for protein expression analysis. RESULTS: The results showed that Phloretin suppressed the proliferation rate of the human SCC-1 oral cancer cells and showed an IC50 of 12.5 µM. Nonetheless, Phloretin had negligible effects on the proliferation rate of the EBTr normal oral cells. DAPI staining showed that Phloretin did not induce apoptosis and western blot showed that it had no apparent effects on the Bax and Bcl-2 expression. Nonetheless annexin V/PI staining showed that Phloretin caused cell death in SCC-1 oral cancer cells. Flow cytometric analysis showed that Phloretin caused increase in the reactive oxygen species (ROS) levels of the SCC-1 cells in a time and dose-dependent manner. Cell cycle analysis showed that Phloretin caused increase in the percentage of the SCC-1 cells in the G0/G1 phase of the cell cycle leading to G0/G1 cell cycle arrest. The G0/G1 arrest of SCC-1 cells was also associated with depletion of cyclin D1, CDK4 and CDK6 expression. Wound healing assay was also performed which showed that Phloretin suppressed the migration of the SCC-1 oral cancer cells, indicative of the anti-metastatic potential of Phloretin. CONCLUSION: Phloretin exhibits significant growth inhibitory effects on the human oral cancer cells and may prove beneficial in oral cancer treatment.

Acupuncture at Zusanli (ST36) for Experimental Sepsis: A Systematic Review.

BACKGROUND: Sepsis is a global major health problem with high mortality rates. More effective therapy is needed for treating sepsis. Acupuncture has been used for various diseases, including severe infection, in China for more than 2,000 years. Previous studies reported that acupuncture at Zusanli (ST36) might be effective in treating sepsis, but the efficacy and the quality of evidence remain unclear since there is no systematic review on acupuncture at ST36 for sepsis. METHODS: Seven databases were searched from the inception of each database up to May 2019. Ultimately, 54 studies using acupuncture at ST36 for the treatment of experimental sepsis were identified in both English and Chinese literature with systematic review procedures. RESULTS: Acupuncture might be useful in reducing injuries induced by sepsis in cardiac, lung, kidney, liver, gastrointestinal tract, and immune system. Its potential mechanisms for antisepsis might include reducing oxidative stress and inflammation, improving microcirculatory disturbance, and maintaining the immune balance mediated by dopamine. However, the positive findings should be interpreted with caution due to poor methodological quality and publication bias. CONCLUSION: Acupuncture at ST36 might be a promising complementary strategy for controlling sepsis inflammation, yet further studies are needed.

A Highly Efficient Tumor-Targeting Nanoprobe with a Novel Cell Membrane Permeability Mechanism.

Efficient tumor targeting has been a great challenge in the clinic for a very long time. The traditional targeting methods based on enhanced permeability and retention (EPR) effects show only an ≈5% targeting rate. To solve this problem, a new graphene-based tumor cell nuclear targeting fluorescent nanoprobe (GTTN), with a new tumor-targeting mechanism, is developed. GTTN is a graphene-like single-crystalline structure amphiphilic fluorescent probe with a periphery that is functionalized by sulfonic and hydroxyl groups. This probe has the characteristic of specific tumor cell targeting, as it can directly cross the cell membrane and specifically target to the tumor cell nucleus by the changed permeability of the tumor cell membranes in the tumor tissue. This new targeting mechanism is named the cell membrane permeability targeting (CMPT) mechanism, which is very different from the EPR effect. These probes can recognize tumor tissue at a very early stage and track the invasion and metastasis of tumor cells at the single cell level. The tumor-targeting rate is improved from less than 5% to more than 50%. This achievement in efficient and accurate tumor cell targeting will speed up the arrival of a new era of tumor diagnosis and treatment.

Tumor Targeting Strategies of Smart Fluorescent Nanoparticles and Their Applications in Cancer Diagnosis and Treatment.

Advantages such as strong signal strength, resistance to photobleaching, tunable fluorescence emissions, high sensitivity, and biocompatibility are the driving forces for the application of fluorescent nanoparticles (FNPs) in cancer diagnosis and therapy. In addition, the large surface area and easy modification of FNPs provide a platform for the design of multifunctional nanoparticles (MFNPs) for tumor targeting, diagnosis, and treatment. In order to obtain better targeting and therapeutic effects, it is necessary to understand the properties and targeting mechanisms of FNPs, which are the foundation and play a key role in the targeting design of nanoparticles (NPs). Widely accepted and applied targeting mechanisms such as enhanced permeability and retention (EPR) effect, active targeting, and tumor microenvironment (TME) targeting are summarized here. Additionally, a freshly discovered targeting mechanism is introduced, termed cell membrane permeability targeting (CMPT), which improves the tumor-targeting rate from less than 5% of the EPR effect to more than 50%. A new design strategy is also summarized, which is promising for future clinical targeting NPs/nanomedicines design. The targeting mechanism and design strategy will inspire new insights and thoughts on targeting design and will speed up precision medicine and contribute to cancer therapy and early diagnosis.