SHP-1 Regulates CD8+ T Cell Effector Function but Plays a Subtle Role with SHP-2 in T Cell Exhaustion Due to a Stage-Specific Nonredundant Functional Relay.

SHP-1 (Src homology region 2 domain-containing phosphatase 1) is a well-known negative regulator of T cells, whereas its close homolog SHP-2 is the long-recognized main signaling mediator of the PD-1 inhibitory pathway. However, recent studies have challenged the requirement of SHP-2 in PD-1 signaling, and follow-up studies further questioned the alternative idea that SHP-1 may replace SHP-2 in its absence. In this study, we systematically investigate the role of SHP-1 alone or jointly with SHP-2 in CD8+ T cells in a series of gene knockout mice. We show that although SHP-1 negatively regulates CD8+ T cell effector function during acute lymphocytic choriomeningitis virus (LCMV) infection, it is dispensable for CD8+ T cell exhaustion during chronic LCMV infection. Moreover, in contrast to the mortality of PD-1 knockout mice upon chronic LCMV infection, mice double deficient for SHP-1 and SHP-2 in CD8+ T cells survived without immunopathology. Importantly, CD8+ T cells lacking both phosphatases still differentiate into exhausted cells and respond to PD-1 blockade. Finally, we found that SHP-1 and SHP-2 suppressed effector CD8+ T cell expansion at the early and late stages, respectively, during chronic LCMV infection.

Two Birds with One Stone: V4 C3 MXene Synergistically Promoted VS2 Cathode and Zinc Anode for High-Performance Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries (AZIBs) are considered to be a rising star in the large-scale energy storage area because of their low cost and environmental friendliness properties. However, the limited electrochemical performance of the cathode and severe zinc dendrite of the anode severely hinder the practical application of AZIBs. Herein, a novel 3D interconnected VS2 ⊥V4 C3 Tx heterostructure material is prepared via one-step solvothermal method. Morphological and structural characterizations show that VS2 nanosheets are uniformly and dispersedly distributed on the surface of the V4 C3 MXene substrate, which can effectively suppress volume change of the VS2 . Owing to the open heterostructure along with the high conductivity of V4 C3 MXene, the VS2 ⊥V4 C3 Tx cathode shows a high specific capacity of 273.9 mAh g-1 at 1 A g-1 and an excellent rate capability of 143.2 mAh g-1 at 20 A g-1 . The V4 C3 MXene can also effectively suppress zinc dendrite growth when used as protective layer for the Zn anode, making the V4 C3 Tx @Zn symmetric cell with a stable voltage profile for ≈1700 h. Benefitting from the synergistic modification effect of V4 C3 MXene on both the cathode and anode, the VS2 ⊥V4 C3 Tx ||V4 C3 Tx @Zn battery exhibits a long cycling lifespan of 5000 cycles with a capacity of 157.1 mAh g-1 at 5A g-1 .

AKR1B10 negatively regulates autophagy through reducing GAPDH upon glucose starvation in colon cancer.

Autophagy is considered to be an important switch for facilitating normal to malignant cell transformation during colorectal cancer development. Consistent with other reports, we found that the membrane receptor Neuropilin1 (NRP1) is greatly upregulated in colon cancer cells that underwent autophagy upon glucose deprivation. However, the mechanism underlying NRP1 regulation of autophagy is unknown. We found that knockdown of NRP1 inhibits autophagy and largely upregulates the expression of aldo-keto reductase family 1 B10 (AKR1B10). Moreover, we demonstrated that AKR1B10 interacts with and inhibits the nuclear importation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and then subsequently represses autophagy. Interestingly, we also found that an NADPH-dependent reduction reaction could be induced when AKR1B10 interacts with GAPDH, and the reductase activity of AKR1B10 is important for its repression of autophagy. Together, our findings unravel a novel mechanism of NRP1 in regulating autophagy through AKR1B10.

Carbon Foam-Supported VS2 Cathode for High-Performance Flexible Self-Healing Quasi-Solid-State Zinc-Ion Batteries.

As the new generation of energy storage systems, the flexible battery can effectively broaden the application area and scope of energy storage devices. Flexibility and energy density are the two core evaluation parameters for the flexible battery. In this work, a flexible VS2 material (VS2 @CF) is fabricated by growing the VS2 nanosheet arrays on carbon foam (CF) using a simple hydrothermal method. Benefiting from the high electric conductivity and 3D foam structure, VS2 @CF shows an excellent rate capability (172.8 mAh g-1 at 5 A g-1 ) and cycling performance (130.2 mAh g-1 at 1 A g-1 after 1000 cycles) when it served as cathode material for aqueous zinc-ion batteries. More importantly, the quasi-solid-state battery VS2 @CF//Zn@CF assembled by the VS2 @CF cathode, CF-supported Zn anode, and a self-healing gel electrolyte also exhibits excellent rate capability (261.5 and 149.8 mAh g-1 at 0.2 and 5 A g-1 , respectively) and cycle performance with a capacity of 126.6 mAh g-1 after 100 cycles at 1 A g-1 . Moreover, the VS2 @CF//Zn@CF full cell also shows good flexible and self-healing properties, which can be charged and discharged normally under different bending angles and after being destroyed and then self-healing.

Alcohol-dependent downregulation of apolipoprotein H exacerbates fatty liver and gut microbiota dysbiosis in mice.

BACKGROUND: Alcohol-related liver disease (ALD) is a major chronic liver ailment caused by alcohol overconsumption and abuse. Apolipoprotein H (APOH) participates in lipid metabolism and might have a potential regulatory role in ALD. Therefore, this study aimed to explore the effects of ApoH on alcohol-induced liver injury and gut microbiota dysbiosis. METHODS: ApoH-/- mice were generated and the synergic alcoholic steatohepatitis mouse model was constructed, which were used to assess liver function and pathological changes. RESULTS: ApoH-/- mice clearly exhibited spontaneous steatohepatitis. Severe hepatic steatosis was observed in alcohol-fed WT and ApoH-/- mice, in which ApoH expression was reduced post alcohol consumption. Moreover, RNA-seq and KEGG pathway analyses indicated that differential expression genes enriched in lipid metabolism and oxidation-reduction process between in alcohol-fed ApoH-/- mice and pair-fed control mice. Finally, gut microbiota diversity and composition were assessed by 16S rRNA Illumina next-generation sequencing. Alpha diversity of enterobacteria was lower in ApoH-/- mice with ethanol feeding than in ethanol-fed WT mice and all control-fed mice (P < 0.05). Moreover, KEGG enrichment analysis, using PICRUSt software, revealed that metabolic functions were activated in the gut microorganisms of ApoH-/- mice with ethanol feeding (P < 0.05). CONCLUSIONS: Alcohol-downregulated ApoH expression, leading to the progress of fatty liver disease and gut microbiota dysbiosis.

Rate Performance Modification of a Lithium-Rich Manganese-Based Material through Surface Self-Doping and Coating Strategies.

Lithium-rich manganese-based materials are currently considered to be highly promising cathode materials for next-generation lithium-ion batteries due to their high specific capacity (>250 mA h g-1) and low cost. A key challenge for the commercialization of these lithium-rich manganese-based materials is their poor rate performance, which is caused by the low electronic conductivity and increasing interface charge transfer resistance produced by the side reaction during the cycling procedure. In this work, we try to improve the rate performance of a lithium-rich manganese-based material Li1.2Mn0.54Co0.13Ni0.13O2 using a collaborative approach with Co-doping and NaxCoO2-coating methods. Cobalt doping can improve the electronic conductivity, and NaxCoO2 coating provides a convenient lithium-ion diffusion channel and moderately alleviates the inevitable decrease in cycling stability caused by cobalt doping. Under the synergistic effect of these two modification strategies, the surface and internal dynamics of the Li1.2Mn0.54Co0.13Ni0.13O2 material are enhanced and its rate performance is considerably improved without decay of the cycle stability.

Quantification of Dynamic Protein Interactions and Phosphorylation in LPS Signaling Pathway by SWATH-MS.

Lipopolysaccharide (LPS)-induced macrophage activation is a prototype of innate immune response. Although key effector proteins in LPS signaling pathway have been revealed, the map of dynamic protein interactions and phosphorylation as well as the stoichiometry of protein complexes are lacking. Here we present a dynamic map of protein interactions and phosphorylation in MyD88, TRAF6 and NEMO complexes obtained by SWATH-MS. The comprehensive MS measurement leads to quantification of up to about 3,000 proteins across about 21-40 IP samples. We detected and quantified almost all known interactors of MyD88, TRAF6 and NEMO. By analyzing these quantitative data, we uncovered differential recruitment of IRAK family proteins to LPS-induced signaling complexes and determined the stoichiometry of the Myddosome complex. In addition, quantitative phosphoproteomics analysis identified a number of unreported high-confidence phosphosites on the key proteins in LPS signaling pathway. Collectively, data of dynamic protein interactions and phosphorylation presented by this study could be a resource for further study of the LPS signaling pathway.

Fast Noninvasive Measurement of Brown Adipose Tissue in Living Mice by Near-Infrared Fluorescence and Photoacoustic Imaging.

Aberrant brown adipose tissue (BAT) metabolism is linked to obesity as well as other metabolic disorders. However, the paucity of imaging tools limits the study of in vivo BAT metabolism in animal models. The current work evaluated a heptamethine dye (CyHF-8) in living mice as a dual-modality BAT-avid molecular probe for two imaging approaches, including near-infrared fluorescence imaging (NIRF) and photoacoustic imaging (PAI). CyHF-8 exhibited favorable spectral properties in the near-infrared window (786/787/805 nm) and accumulated in the subcellular mitochondria of brown adipocytes. After intravenous injection of CyHF-8, NIRF and PAI were both capable of noninvasively detecting interscapular BAT at early time points in living mice. Quantitative analysis of NIRF and PAI images showed that CyHF-8 signals respond to dynamic BAT changes in mice stimulated by norepinephrine (NE) and in diabetic mice induced by streptozotocin (STZ). In summary, dual-modality NIRF/PAI probe CyHF-8 can be used for both NIRF and PAI to noninvasively assess BAT metabolism in living animals.

Fiber Optic Particle Plasmon Resonance Biosensor for Label-Free Detection of Nucleic Acids and Its Application to HLA-B27 mRNA Detection in Patients with Ankylosing Spondylitis.

We developed a label-free, real-time, and highly sensitive nucleic acid biosensor based on fiber optic particle plasmon resonance (FOPPR). The biosensor employs a single-strand deoxyoligonucleotides (ssDNA) probe, conjugated to immobilized gold nanoparticles on the core surface of an optical fiber. We explore the steric effects on hybridization affinity and limit of detection (LOD), by using different ssDNA probe designs and surface chemistries, including diluent molecules of different lengths in mixed self-assembled monolayers, ssDNA probes of different oligonucleotide lengths, ssDNA probes in different orientations to accommodate target oligonucleotides with a hybridization region located unevenly in the strand. Based on the optimized ssDNA probe design and surface chemistry, we achieved LOD at sub-nM level, which makes detection of target oligonucleotides as low as 1 fmol possible in the 10-mL sensor chip. Additionally, the FOPPR biosensor shows a good correlation in determining HLA-B27 mRNA, in extracted blood samples from patients with ankylosing spondylitis (AS), with the clinically accepted real-time reverse transcription-polymerase chain reaction (RT-PCR) method. The results from this fundamental study should guide the design of ssDNA probe for anti-sense sensing. Further results through application to HLA-B27 mRNA detection illustrate the feasibility in detecting various nucleic acids of chemical and biological relevance.

[Expression of gap junction protein connexin 26 in human hepatocellular carcinoma and its significance].

OBJECTIVE: To investigate the expression of gap junction protein connexin 26(Cx26) in hepatocellular carcinoma(HCC) and its significance. METHODS: The expression of Cx26 in liver tissue was examined by immunohistochemistry staining in 159 paraffin-embeded liver sections, including 20 samples of normal liver tissue, 30 samples of chronic hepatitis, 33 samples of liver cirrhosis, and 76 samples of HCC. Normal hepatic cell line LO2 and HCC cell line SMMC-7721 were used in vitro to verify the characteristics of gap junction and Cx26 expression pattern. The expression and localization of Cx26 were measured by Western blotting and immunofluorescence assay, respectively. The function of gap junction between adjacent cells was detected by dye transfer assay. RESULTS: Compared to normal liver samples, the positive rate of Cx26 was markedly decreased in hepatitis, cirrhosis and HCC tissues(all P<0.05). The intensity of Cx26 staining was significantly increased in HCC tissues compared with those in non-carcinomatous liver(NCL) tissues(all P<0.05). In NCL tissues, there was a mild to moderated staining of Cx26 which located mainly on the membranes of hepatocytes at intercellular contacts. The positive staining of Cx26 in HCC tissues was observed mainly in cytoplasm. Positive Cx26 expression was positively associated with tumor size(P=0.036), but not with age, gender, histologic grade, clinical stage, underlying hepatitis and cirhosis, lymph node metastasis and intrahepatic vascular embolism(all P>0.05). Compared with LO2 cells, an aberrant expression and distribution of Cx26 in SMMC-7721 cells was confirmed, which may lead to a decreased function of gap junctions. CONCLUSIONS: The aberrant expression and distribution of Cx26 protein may be associated with hepatocarcinogenesis, and the residual gap junction in HCC may provide a new target for treatment of HCC.

Surface Modification Driven Initial Coulombic Efficiency and Rate Performance Enhancement of Li1.2 Mn0.54 Ni0.13 Co0.13 O2 Cathode.

Due to its high energy density and low cost, Li-rich Mn-based layered oxides are considered potential cathode materials for next generation Li-ion batteries. However, they still suffer from the serious obstacle of low initial Coulombic efficiency, which is detrimental to their practical application. Here, an efficient surface modification method via NH4 H2 PO4 assisted pyrolysis is performed to improve the Coulombic efficiency of Li1.2 Mn0.54 Ni0.13 Co0.13 O2 , where appropriate oxygen vacancies, Li3 PO4 and spinel phase are synchronously generated in the surface layer of LMR microspheres. Under the synergistic effect of the oxygen vacancies and spinel phase, the unavoidable oxygen release in the cycling process was effectively suppressed. Moreover, the induced Li3 PO4 nanolayer could boost the lithium-ion diffusion and mitigate the dissolution of transition metal ions, especially manganese ions, in the material. The optimally modified sample yielded an impressive initial Coulombic efficiency and outstanding rate performance.

Dynamics of Endophytic Fungal Communities Associated with Cultivated Medicinal Plants in Farmland Ecosystem.

Microorganisms are an important component of global biodiversity and play an important role in plant growth and development and the protection of host plants from various biotic and abiotic stresses. However, little is known about the identities and communities of endophytic fungi inhabiting cultivated medicinal plants in the farmland ecosystem. The diversity and community composition of the endophytic fungi of cultivated medicinal plants in different hosts, tissue niches, and seasonal effects in the farmland of Northern China were examined using the next-generation sequencing technique. In addition, the ecological functions of the endophytic fungal communities were investigated by combining the sequence classification information and fungal taxonomic function annotation. A total of 1025 operational taxonomic units (OTUs) of endophytic fungi were obtained at a 97% sequence similarity level; they were dominated by Dothideomycetes and Pleosporales. Host factors (species identities and tissue niches) and season had significant effects on the community composition of endophytic fungi, and endophytic fungi assembly was shaped more strongly by host than by season. In summer, endophytic fungal diversity was higher in the root than in the leaf, whereas opposite trends were observed in winter. Network analysis showed that network connectivity was more complex in the leaf than in the root, and the interspecific relationship between endophytic fungal OTUs in the network structure was mainly positive rather than negative. The functional predications of fungi revealed that the pathotrophic types of endophytic fungi decreased and the saprotrophic types increased from summer to winter in the root, while both pathotrophic and saprotrophic types of endophytic fungi increased in the leaf. This study improves our understanding of the community composition and ecological distribution of endophytic fungi inhabiting scattered niches in the farmland ecosystem. In addition, the study provides insight into the biodiversity assessment and management of cultivated medicinal plants.

Crystallinity Tuning of Na3 V2 (PO4 )3 : Unlocking Sodium Storage Capacity and Inducing Pseudocapacitance Behavior.

As a promising cathode material of sodium-ion batteries, Na3 V2 (PO4 )3 (NVP) has attracted extensive attention in recent years due to its high stability and fast Na+ ion diffusion. However, the reversible capacity based on the two-electron reaction mechanism is not satisfactory limited by the inactive M1 lattice sites during the insertion/extraction process. Herein, self-supporting 3D porous NVP materials with different crystallinity are fabricated on carbon foam substrates by a facile electrostatic spray deposition method. The V5+ /V4+ redox couple is effectively activated and the three-electron reactions are realized in NVP for sodium storage by a proper crystallinity tuning. In a disordered NVP sample, an ultra-high specific capacity of 179.6 mAh g-1 at 0.2 C is achieved due to the coexistence of redox reactions of the V4+ /V3+ and V5+ /V4+ couples. Moreover, a pseudocapacitive charge storage mechanism induced by the disordered structure is first observed in the NVP electrode. An innovative model is given to understand the disorder-induced-pseudocapacitance phenomenon in this polyanion cathode material.

Magneto-electrochemistry driven ultralong-life Zn-VS2 aqueous zinc-ion batteries.

The development of high energy density and long cycle lifespan aqueous zinc ion batteries is hindered by the limited cathode materials and serious zinc dendrite growth. In this work, a defect-rich VS2 cathode material is manufactured by in situ electrochemical defect engineering under high charge cut-off voltage. Owing to the rich abundant vacancies and lattice distortion in the ab plane, the tailored VS2 can unlock the transport path of Zn2+ along the c-axis, enabling 3D Zn2+ transport along both the ab plane and c-axis, and reduce the electrostatic interaction between VS2 and zinc ions, thus achieving excellent rate capability (332 mA h g-1 and 227.8 mA h g-1 at 1 A g-1 and 20 A g-1, respectively). The thermally favorable intercalation and 3D rapid transport of Zn2+ in the defect-rich VS2 are verified by multiple ex situ characterizations and density functional theory (DFT) calculations. However, the long cycling stability of the Zn-VS2 battery is still unsatisfactory due to the Zn dendrite issue. It can be found that the introduction of an external magnetic field enables changing the movement of Zn2+, suppressing the growth of zinc dendrites, and resulting in enhanced cycling stability from about 90 to 600 h in the Zn||Zn symmetric cell. As a result, a high-performance Zn-VS2 full cell is realized by operating under a weak magnetic field, which shows an ultralong cycle lifespan with a capacity of 126 mA h g-1 after 7400 cycles at 5 A g-1, and delivers the highest energy density of 304.7 W h kg-1 and maximum power density of 17.8 kW kg-1.

GIPC1 promotes tumor growth and migration in gastric cancer via activating PDGFR/PI3K/AKT signaling.

The high mortality rate associated with gastric cancer (GC) has resulted in an urgent need to identify novel therapeutic targets for GC. This study aimed to investigate whether GAIP interacting protein, C terminus 1 (GIPC1) represents a therapeutic target and its regulating mechanism in GC. GIPC1 expression was elevated in GC tissues, liver metastasis tissues, and lymph node metastases. GIPC1 knockdown or GIPC1 blocking peptide blocked the platelet-derived growth factor receptor (PDGFR)/PI3K/AKT signaling pathway, and inhibited the proliferation and migration of GC cells. Conversely, GIPC1 overexpression markedly activated the PDGFR/PI3K/AKT signaling pathway, and promoted GC cell proliferation and migration. Furthermore, platelet-derived growth factor subunit BB (PDGF-BB) cytokines and the AKT inhibitor attenuated the effect of differential GIPC1 expression. Moreover, GIPC1 silencing decreased tumor growth and migration in BALB/c nude mice, while GIPC1 overexpression had contrasting effects. Taken together, our findings suggest that GIPC1 functions as an oncogene in GC and plays a central role in regulating cell proliferation and migration via the PDGFR/PI3K/AKT signaling pathway.

Themis suppresses the effector function of CD8+ T cells in acute viral infection.

CD8+ T cells play a central role in antiviral immune responses. Upon infection, naive CD8+ T cells differentiate into effector cells to eliminate virus-infected cells, and some of these effector cells further differentiate into memory cells to provide long-term protection after infection is resolved. Although extensively investigated, the underlying mechanisms of CD8+ T-cell differentiation remain incompletely understood. Themis is a T-cell-specific protein that plays critical roles in T-cell development. Recent studies using Themis T-cell conditional knockout mice also demonstrated that Themis is required to promote mature CD8+ T-cell homeostasis, cytokine responsiveness, and antibacterial responses. In this study, we used LCMV Armstrong infection as a probe to explore the role of Themis in viral infection. We found that preexisting CD8+ T-cell homeostasis defects and cytokine hyporesponsiveness do not impair viral clearance in Themis T-cell conditional knockout mice. Further analyses showed that in the primary immune response, Themis deficiency promoted the differentiation of CD8+ effector cells and increased their TNF and IFNγ production. Moreover, Themis deficiency impaired memory precursor cell (MPEC) differentiation but promoted short-lived effector cell (SLEC) differentiation. Themis deficiency also enhanced effector cytokine production in memory CD8+ T cells while impairing central memory CD8+ T-cell formation. Mechanistically, we found that Themis mediates PD-1 expression and its signaling in effector CD8+ T cells, which explains the elevated cytokine production in these cells when Themis is disrupted.

Intercalation Reaction in Amorphous Layer-Wrapped Ni0.2Mo0.8N/Ni3N Heterostructure Toward Efficient Lithium-Ion Storage.

Transition metal nitrides (TMNs) with high specific capacity and electric conductivity have drawn considerable attention as electrode materials of lithium-ion batteries (LIBs). However, the cycling stability of most TMNs is not satisfactory, which was caused by the large volume variation during cycles due to their intrinsic conversion reaction mechanism. Herein, by rational design, a much stable tremella-like Ni0.2Mo0.8N/Ni3N heterostructure with amorphous Ni0.2Mo0.8N wrapped layer has been fabricated. The Ni3N particles worked as pillars to support the Ni0.2Mo0.8N material as well as conductive medium to facilitate ionic and electronic transport. The amorphous layer can relieve the structural stress of Ni0.2Mo0.8N during cycles. Moreover, an exotic intercalation-type reaction mechanism in the ternary nitride Ni0.2Mo0.8N was revealed by a series ex situ and in situ characterization. Profiting from these advantages, the Ni0.2Mo0.8N/Ni3N heterostructure anode displays an outstanding electrochemical performance with a high initial reversible discharge capacity of 1001.6 mA h g-1 at 0.1 A g-1, excellent cycle stability of 695.5 mA h g-1 at 2 A g-1 after 600 cycles, and superior rate capability of 595.3 mA h g-1 at a high current density of 5 A g-1. This work provides a new insight for designing high efficiency LIBs based on intercalation reaction for practical applications.

AKR1B10 accelerates the production of proinflammatory cytokines via the NF-κB signaling pathway in colon cancer.

Aldo-keto reductase family one, member B10 (AKR1B10) has been reported to be involved in the tumorigenesis of various cancers. It has been reported that colorectal cancer is closely associated with chronic inflammation, but the underlying molecular mechanisms are still elusive. In our study, we evaluated the relationship between AKR1B10 expression and clinicopathological characteristics of colon cancer and showed that AKR1B10 expression was significantly correlated with the T stage and clinical stage of colon cancer. Knockdown of AKR1B10 significantly decreased the expression of the inflammatory cytokines IL1α and IL6 induced by lipopolysaccharide by inhibiting the NF-κB signaling pathway. Furthermore, AKR1B10 depends on its reductase activity to affect the NF-κB signaling pathway and subsequently affect the production of inflammatory cytokines. In addition, knockdown of AKR1B10 effectively reduced cell proliferation and clonogenic growth, indicating the biological role of AKR1B10 in colon cancer. Together, our findings provide important insights into a previously unrecognized role of AKR1B10 in colon cancer.

Synthesis of a New Water-Soluble Melatonin Derivative with Low Toxicity and a Strong Effect on Sleep Aid.

A new melatonin sulfonate derivative sodium 4-(3-(2-acetamidoethyl)-5-methoxy-1H-indol-1-yl) butane-1-sulfonate (MLTBS) with higher water solubility (695 times) and lower cytotoxicity than natural melatonin (MLT) was synthesized, yet with the same sleep aid function. The poor solubility of MLT in water has been improved with a simple chemical reaction, which solves the poor solubility of melatonin in water, overcoming the safety problem caused by adding organic reagents such as dimethyl sulfoxide (DMSO) and ethanol to increase the solubility. Moreover, the modified MLT still has the same sleep aid effect as the natural MLT and higher biological safety. As a novel potential drug for sleep aid, the new MLT derivative could also flourish the application and research of this molecule in medicine and biology.

Anticancer effect of LS-HB-mediated photodynamic therapy on hepatocellular carcinoma in vitro and in vivo.

Photodynamic therapy (PDT) is a relatively safe way for disease diagnosis and treatment that is based on light and photosensitizers. LS-HB is a promising photosensitizer with a light absorption peak of 660 nm. AIMS: The present study aimed to investigate the anticancer effects of LS-HB-PDT on hepatocellular carcinoma and its underlying molecular mechanism. METHODS: In the present study, the MTT assay and xenograft tumor model experiment were used to evaluate its anticancer effects as well as its dark toxicity in hepatocellular carcinoma in vitro and in vivo. Reactive oxygen species assay kit was utilized to detect the reactive oxygen species production induced by LS-HB-PDT. RESULTS: In vitro, the MTT assay results revealed that LS-HB-PDT exhibited significant cytotoxic effects both in a drug- and light dose-dependent manner. The IC50 of LS-HB-PDT on hepatocellular carcinoma cells was 2.685 µg/ml. However, no dark cytotoxicity was observed at the LS-HB concentrations of 0-50 µg/ml, and no light-induced cytotoxicity was observed at the light (660 nm) dosages of 0-40 J/cm2. Furthermore, reactive oxygen species could be induced after LS-HB-PDT in a drug- and light dose-dependent manner. In vivo experiment, the tumor inhibition ratio of tumor-bearing nude mice following LS-HB-PDT was enhanced with the drug and light dose increasing. Notably, tumors in 60.0% of mice disappeared after LS-HB-PDT (2 mg/kg; 100 J/cm2), and the tumor inhibition ratio reached 92.3%. Furthermore, the histological results revealed necrosis and thrombus in tumor tissue caused by LS-HB-PDT, which were not observed in the control, drug alone and light alone groups of mice. CONCLUSIONS: The present study indicated that LS-HB was a promising photosensitizer with excellent anticancer effects and low side effects. LS-HB-PDT induced reactive oxygen species damage in the cells directly and destroyed tumor blood vessels, thus leading to tumor tissue necrosis.