Prenatal to peripubertal exposure to Di(2-ethylhexyl) phthalate induced endometrial atrophy and fibrosis in female mice.

Di(2-ethylhexy) phthalate (DEHP) is a widely used plasticizer that is ubiquitously found in the environment. Using a mouse model, we investigated the impact of early life DEHP exposure ranging from the prenatal to peripubertal developmental period of the female reproductive system. Pregnant female mice were allocated to three groups as follows: control, 100 mg/kg/day, and 500 mg/kg/day DEHP treatment. DEHP exposure was introduced through feeding during pregnancy (3 weeks) and lactation (3 weeks). After weaning, the offspring were also exposed to DEHP through feeding for another 2 weeks. Observations were conducted on female offspring at 10 and 24 weeks. The number of live offspring per dam was significantly lower in the high-DEHP-exposed group (500 mg/kg/day) compared to the control group (7.67 ± 1.24 vs. 14.17 ± 0.31; p < 0.05) despite no difference in pregnancy rates across the groups. Low-DEHP exposure (100 mg/kg/day) resulted to a decreased body weight (36.07 ± 3.78 vs. 50.11 ± 2.11 g; p < 0.05) and decreased left uterine length (10.60 ± 1.34 vs. 14.77 ± 0.82 mm; p < 0.05) in 24-week- old female mice. As early as 10 weeks, endometrial atrophy and fibrosis were observed, and endometrial cystic hyperplasia was noted in female mice at 24 weeks. Our study is the first to demonstrate that female mice exposed to DEHP in the early life developed endometrial fibrosis in the female offspring. Further studies on the consequences of these observations in fecundity and other reproductive functions are warranted.

Genetic analysis of a novel antioxidant multi-target iron chelator, M30 protecting against chemotherapy-induced alopecia in mice.

BACKGROUND: Chemotherapy-induced alopecia has been well documented as a cause of distress to patients undergoing cancer treatment. Almost all traditional chemotherapeutic agents cause severe alopecia. Despite advances in the treatment of chemotherapy-induced alopecia, there is no effective treatment for preventing chemotherapy-induced alopecia. METHODS: In the present study, we investigated the potential role of a multi-target iron chelator, M30 in protecting against cyclophosphamide-induced alopecia in C57BL/6 mice implanted with an osmotic pump. M30 enhanced hair growth and prevented cyclophosphamide-induced abnormal hair in the mice. Furthermore, we examined the gene expression profiles derived from skin biopsy specimens of normal mice, cyclophosphamide-treated mice, and cyclophosphamide treated mice with M30 supplement. RESULTS: The top genes namely Tnfrsf19, Ercc2, Lama5, Ctsl, and Per1 were identified by microarray analysis. These genes were found to be involved in the biological processes of hair cycle, hair cycle phase, hair cycle process, hair follicle development, hair follicle maturation, hair follicle morphogenesis, regulation of hair cycle. CONCLUSION: Our study demonstrates that M30 treatment is a promising therapy for cyclophosphamide-induced alopecia and suggests that the top five genes have unique preventive effects in cyclophosphamide-induced transformation.

Effects of Various Hybrid Carbon Matrices on the ZnSe Composite Anode for Lithium-Ion Batteries.

Zinc selenide-based hybrid carbon composites were synthesized by a high-energy mechanical milling process under an Ar atmosphere. The as-synthesized ZnSe-based carbon composites were characterized by X-ray diffraction and transmission electron microscopy. First, we examined the effect of single-component carbon matrices on the electrochemical performance of ZnSe. The results showed the best performance for graphite (G), followed by carbon nanotubes (CNTs), and amorphous carbon. Based on these results, in order to further enhance the performance of ZnSe, we introduced a binary-carbon matrix consisting of graphite and CNTs at various ratios of 1:1, 1:3, and 3:1, respectively. As a result, ZnSe©G/CNT (1:3) exhibited the best performance in terms of cyclic life and rate capability. Specifically, ZnSe©G/CNT (1:3) delivered a specific capacity of 1041 mAh g-1 at a current density of 100 mA g-1 after 300 cycles with a coulombic efficiency of over 99% with high rate performance.

Facile and Scalable Preparation of a MoS2/Carbon Nanotube Nanocomposite Anode for High-Performance Lithium-Ion Batteries: Effects of Carbon Nanotube Content.

To investigate the effects of carbon nanotube content on the electrochemical performance in MoS2/CNT nanocomposite, a simple high-energy mechanical milling method was employed to prepare nanocomposites from MoS2 and CNT. Prepared with a one-step, 24-h ball-milling method, the MoS2/CNT nanocomposite showed improved performance in terms of specific capacity after 70 cycles when compared to pure MoS2. In addition, upon studying the effects of the weight ratio between MoS2 and the CNTs at (1:2), (1:1), and (2:1), we found the MoS2/CNT-(1:2) showed the highest specific capacity (~765 mAh g-1) after 70 cycles and the best rate capability due to increased conductivity. Overall, the results suggested that the addition of conductive CNTs in MoS2 not only improves the cycling stability, but also leads to an increase in the specific capacity of MoS2/CNTs, which suggests our MoS2/CNT nanocomposite as a new and promising anode material for lithium-ion batteries (LIBs).

Comparison between Fractionated Dose and Single Dose of Cu-64 Trastuzumab Therapy in the NCI-N87 Gastric Cancer Mouse Model.

For optimum radioimmunotherapy (RIT), deep penetration and uniform distribution into the tumor core is important. The solid tumor microenvironment, consisting of a highly fibrotic or desmoplastic tumor, abnormal tumor vasculature, high fluid pressure, and the absence of fluid lymphatics, limits the distribution of monoclonal antibodies mAbs to the tumor core. To investigate the optimal rationale for therapeutic mAbs administration and the microdistribution of mAbs, single and serial fractional dosage regimens of Cu-64-trastuzumab (TRZ) with paclitaxel were evaluated. Groups of nude mice were inoculated with gastric cancer cell line NCI-N87 tumor cells. When the tumor size reached 200 ± 20 mm3, the mice were divided into two groups for injection of Alexa-647-TRZ. One group (n = 5) was injected with 15 mg/kg in a single dose (SD), and the other group (n = 5) with two doses of 7.5 mg/kg (fractionated dose (FD)). In both cases, the injections were done intravenously in combination with intraperitoneal paclitaxel either as a SD of 70 mg/kg or fractionated into two doses of 40 and 30 mg/kg. Tumors were harvested, flash frozen, and sectioned (8 µm) five days after Alexa-647-TRZ injection. Rhodamine lectin (rhodamine-labeled Ricinus communis agglutinin I, 1 mg in 0.2 mL of phosphate-buffered saline (PBS)) was intravenously injected to delineate the functional vessel for a wait time of 5 min before animal euthanization. Microscopic images were acquired with an IN Cell Analyzer. The amount of TRZ that penetrated the tumor surface and the tumor vessel was calculated by area under the curve (AUC) analysis. For RIT efficacy (n = 21), Cu-64-TRZ was injected following the same dose schedule to observe tumor volume and survival ratio for 30 days. The SD and FD regimens of Alexa-647-TRZ were observed to have no significant difference in penetration of mAbs from the tumor edge and vessel, nor was the total accumulation across the whole tumor tissue significantly different. Additionally, the SD and FD regimens of Cu-64-TRZ were not proven to be significantly efficacious. Our study reveals that SD and FD in a treatment design with Cu-64-TRZ and paclitaxel shows no significant difference in therapeutic efficacy on tumor growth inhibition in vivo in mice bearing human gastric cancer xenografts overexpressing HER2 antigen.

Combination Radioimmunotherapy Strategies for Solid Tumors.

Combination radioimmunotherapy is an emerging approach for the treatment of solid tumors where radio immunotherapy alone has proven to be reasonably ineffective. Radioimmunotherapy (RIT) using monoclonal antibodies (mAbs) labeled with radionuclides is an attractive approach for cancer treatment because tumor-associated mAbs with cytotoxic radionuclides can selectively bind to tumor antigens. However, due to various limitations, mAbs cannot reach solid tumors, consequently reducing RIT efficacy. Combination RIT is a pragmatic approach through which the addition of drugs or other agents not only help mAbs to reach the targeted site but also improves its efficacy. Thus, the combination of drugs or moieties with RIT can be applied to overcome the barriers that RIT faces for solid tumors. This review covers the RIT approach, along with the mechanism of action of mAb used in RIT, limitations of solid tumors, and strategies that can be used in combination RIT to enhance the treatment regimen for solid tumors.

Comparative Study of Mechanically Milled MoS2 and MoSe2 in Graphite Matrix as Anode Materials for High-Performance Lithium-Ion Batteries.

Nanocomposites of MoS2/graphite and MoSe2/graphite were formed from two-dimensional materials (MoS2 and MoSe2) and graphite using a one-step ball-milling method (high energy mechanical milling, HEMM). As anode materials for lithium-ion batteries (LIBs), these nanocomposites showed higher specific capacity and greater stability during long cyclic operation compared to their pure counterparts (MoS2 and MoSe2). X-ray diffraction and transmission electron microscopy revealed that graphite nanoflakes were effectively exfoliated and covered MoS2 or MoSe2 layers to form homogeneous nanostructures via HEMM. As a result, the electrochemical performances of both MoS2/graphite and MoSe2/graphite were excellent; the specific capacities were as high as 684.8 (MoS2/graphite) and 787.3 mAh g-1 (MoSe2/graphite) after 100 cycles. Also, when compared with MoS2/graphite, the MoSe2/graphite nanocomposite showed higher specific capacity and better rate capability performance due to larger interlayer spacing, leading to fast and facile movement of Liions. Overall, we demonstrate that homogeneous nanocomposites between similar layered materials (MoS2, MoSe2 and graphite) can be easily synthesized via one-step HEMM, which can be used as excellent anode materials for LIBs.

Functional Biological Activity of Sorafenib as a Tumor-Treating Field Sensitizer for Glioblastoma Therapy.

Glioblastoma, the most common primary brain tumor in adults, is an incurable malignancy with poor short-term survival and is typically treated with radiotherapy along with temozolomide. While the development of tumor-treating fields (TTFields), electric fields with alternating low and intermediate intensity has facilitated glioblastoma treatment, clinical outcomes of TTFields are reportedly inconsistent. However, combinatorial administration of chemotherapy with TTFields has proven effective for glioblastoma patients. Sorafenib, an anti-proliferative and apoptogenic agent, is used as first-line treatment for glioblastoma. This study aimed to investigate the effect of sorafenib on TTFields-induced anti-tumor and anti-angiogenesis responses in glioblastoma cells in vitro and in vivo. Sorafenib sensitized glioblastoma cells to TTFields, as evident from significantly decreased post-TTFields cell viability (p < 0.05), and combinatorial treatment with sorafenib and TTFields accelerated apoptosis via reactive oxygen species (ROS) generation, as evident from Poly (ADP-ribose) polymerase (PARP) cleavage. Furthermore, use of sorafenib plus TTFields increased autophagy, as evident from LC3 upregulation and autophagic vacuole formation. Cell cycle markers accumulated, and cells underwent a G2/M arrest, with an increased G0/G1 cell ratio. In addition, the combinatorial treatment significantly inhibited tumor cell motility and invasiveness, and angiogenesis. Our results suggest that combination therapy with sorafenib and TTFields is slightly better than each individual therapy and could potentially be used to treat glioblastoma in clinic, which requires further studies.

99mTc-DMSA and 99mTc-DTPA identified renal dysfunction due to microplastic polyethylene in murine model.

In the previous study (Im et al., 2022), we revealed microplastic (MP) was accumulated and cleared through the kidneys via PET imaging. Here, we aimed to identify the renal dysfunction due to polyethylene (PE) MP in the kidney tissue. Mice were exposed to 100 ppm (∼equivalent to 0.1 mg/mL)/100 µL of PE for 12 weeks (n = 10). PE uptake in the kidney tissues was confirmed using confocal microscopy. QuantSeq analysis was performed to determine gene expression. Renal function assessment was performed using 99mTc-Diethylene triamine penta acetic acid or 99mTc-Dimercaptosuccinic acid. Measurement of creatinine, BUN, and albumin levels in serum and urine samples was also estimated. [18F]-FDG was also acquired. PE increased expression of Myc, CD44, Programmed Death-Ligand 1 (PD-L1), and Hypoxia-Inducible Factor (HIF)-1α, which indicates a potential link to an increased risk of early-onset cancer. An increase in glucose metabolism of [18F]-FDG were observed. We assessed renal failure using 99mTc-Diethylene triamine penta acetic acid and 99mTc-Dimercaptosuccinic acid scintigraphy to determine the renal function. Renal failure was confirmed using serum and urine creatinine, serum blood urea nitrogen levels, serum albumin levels, and urine albumin levels in PE exposed mice, relative to the control. In sum, PE exposure induced renal dysfunction in a murine model.

Microplastic polyethylene induced inner ear dysfunction in murine model.

While the hazardous effects of microplastics (MPs) are increasingly reported, it remains uncertain if MPs induce inner ear dysfunction. Nonetheless, prevalence of inner ear dysfunction was observed across all age groups. In this study, we investigated whether MP polyethylene affect inner ear function in a murine model. To detect hearing loss and balance defect after polyethylene (PE) exposure, we evaluated hearing threshold levels, assessed cerebral glucose metabolism, conducted transcriptome analysis, and performed behavioral studies. C57BL/6 J mice (5-week-old) were grouped into control (n = 10) and PE-fed groups (n = 10). Mice were orally administered 100 ppm/100 µL (equivalent to 10 µg) of PE every day for 4 months. We identified the accumulation of PE in the cochlea and vestibular region. The fragmented PE in inner ear was 3.00 ± 0.38 µm in size; the administered PE concentration was 1.14 ± 1.06 mg/g. Fourier transform infrared spectrometry confirmed that the properties of the MP were identical with those of PE fed to the mice. Transcriptomic analysis showed up-regulation of PER1, NR4A3 and CEBPB at the PE exposed inner ear tissue and it was confirmed using qRT-PCR, western blotting, and immunofluorescence staining. We observed abnormalities in balance related behavior assessment in the PE group. Exposure to PE increased the hearing thresholds and decreased glucose metabolism in the bilateral lateral entorhinal cortex, right primary auditory cortex, and right secondary auditory cortex. We can conclude that PE exposure induced inner ear dysfunction such as hearing loss and balance disorder.

Enhanced ASGR2 by microplastic exposure leads to resistance to therapy in gastric cancer.

Background: Microplastics (MPs) are a new global environmental threat. Previously, we showed the biodistribution of MPs using [64Cu] polystyrene (PS) and PET in mice. Here, we aimed to identify whether PS exposure has malignant effects on the stomach and induces resistance to therapy. Methods: BALB/c nude mice were fed 1.72 × 104 particles/mL of MP. We investigated PS accumulation in the stomach using radioisotope-labeled and fluorescent-conjugated PS. Further, we evaluated whether PS exposure induced cancer stemness and multidrug resistance, and whether it affected tumor development, tumor growth, and survival rate in vivo using a 4-week PS-exposed NCI-N87 mouse model. Using RNA-Seq analysis, we analyzed whether PS exposure induced gene expression changes in gastric tissues of mice. Results: PET imaging results showed that a single dose of [64Cu]-PS remained for 24 h in the mice stomach. The 4-week daily repetitive dose of fluorescent conjugated PS was deposited in the gastric tissues of mice. When PS was exposed, a 2.9-fold increase in migration rate was observed for NCI-N87 cells. Immunocytochemistry results showed decreased E-cadherin and increased N-cadherin expression, and flow cytometry, qPCR, and western blot analysis indicated a 1.9-fold increase in N-cadherin expression after PS exposure. Further, PS-induced multidrug resistance to bortezomib, paclitaxel, gefitinib, lapatinib, and trastuzumab was observed in the NCI-N87 mouse model due to upregulated CD44 expression. RNA-seq results identified increased asialoglycoprotein receptor 2 (ASGR2) expression after PS exposure, and ASGR2 knockdown decreased cell proliferation, migration, invasion, and drug resistance. Conclusion: We demonstrated that ASGR2 enhanced cancer hallmarks on PS exposure and induced resistance to chemo- and monoclonal antibody-therapy. Our preclinical findings may provide an incentive for further epidemiological studies on the role of MP exposure and its association with gastric cancer.

Correlation between the Cation Disorders of Fe3+ and Li+ in P3-Type Na0.67[Li0.1(Fe0.5Mn0.5)0.9]O2 for Sodium Ion Batteries.

Various Fe-based layered oxide materials have received attention as promising cathode materials for sodium ion batteries because of their low cost and high specific capacity. Only a few P3-type Fe-based oxide materials, however, have been examined as cathodes because the synthesis of highly crystalline P3-type Fe-based oxides is not facile. For this reason, the structural merits of the P3 structure are not yet fully understood. Herein, highly crystalline P3-type Na0.67[Li0.1(Fe0.5Mn0.5)0.9]O2 heated at 900 °C is introduced to improve the electrochemical performance of Fe-based layered oxides. The structures, reaction mechanisms, and electrochemical performances of P3 Na0.67[Li0.1(Fe0.5Mn0.5)0.9]O2, P2 Na0.57[Li0.1(Fe0.5Mn0.5)0.9]O2, and P2 Na0.67[Fe0.5Mn0.5]O2 are compared to demonstrate the roles of Li+ doping in the improved electrochemical performance of P3 Na0.67[Li0.1(Fe0.5Mn0.5)0.9]O2, such as stable capacity retention over 100 cycles. P3 Na0.67[Li0.1(Fe0.5Mn0.5)0.9]O2 significantly suppresses the migration of Fe3+ ions to tetrahedral sites in the Na layer during cycling because the cation disorder of Li+ is more favorable than that of Fe3+. As a result, P3 Na0.67[Li0.1(Fe0.5Mn0.5)0.9]O2 shows better cycle performance than P2 Na0.67[Fe0.5Mn0.5]O2. P3 Na0.67[Li0.1(Fe0.5Mn0.5)0.9]O2 also exhibits an improved rate performance compared to P2 Na0.67[Fe0.5Mn0.5]O2. This finding provides fundamental insights to improve the electrochemical performance of layered oxide cathode materials for sodium ion batteries.

PET Tracing of Biodistribution for Orally Administered 64Cu-Labeled Polystyrene in Mice.

Plastics are used commonly in the world because of their convenience and cost effectiveness. Microplastics, an environmental threat and human health risk, are widely detected in food and consequently ingested. However, degraded plastics are found everywhere, creating an environmental threat and human health risk. Therefore, real-time monitoring of orally administered microplastics to trace them in the body is tremendously important. Methods: In this study, to visualize their absorption path, we labeled polystyrene with [64Cu]Cu-DOTA. We prepared radiolabeled polystyrene with 64Cu. Afterward, [64Cu]Cu-DOTA-polystyrene was orally administered to mice, and we evaluated its transit and absorption using PET imaging. The absorption path and distribution of [64Cu]Cu-DOTA-polystyrene were determined using PET over 48 h. Ex vivo tissue radio-thin-layer chromatography (TLC) was used to demonstrate the existence of [64Cu]Cu-DOTA-polystyrene in tissue. Results: PET images demonstrated that [64Cu]Cu-DOTA-polystyrene began to transit to the intestine within 1 h. Accumulation of [64Cu]Cu-DOTA-polystyrene in the liver was also observed. The biodistribution of [64Cu]Cu-DOTA-polystyrene confirmed the distribution of [64Cu]Cu-DOTA-polystyrene observed on the PET images. Ex vivo radio-TLC demonstrated that the detected γ-rays originated from [64Cu]Cu-DOTA-polystyrene. Conclusion: This study provided PET evidence of the existence and accumulation of microplastics in tissue and cross-confirmed the PET findings by ex vivo radio-TLC. This information may be used as the basis for future studies on the toxicity of microplastics.

Pre/post-natal exposure to microplastic as a potential risk factor for autism spectrum disorder.

In common with the increase in environmental pollution in the past 10 years, there has also been a recent increase in the prevalence of autism spectrum disorder (ASD). In this regard, we hypothesized that exposure to microplastics is a potential risk factor for ASD. To evaluate the validity of this hypothesis, we initially examined the accumulation of polyethylene (PE) in the brains of mice and then assessed the behavioral effects using mouse models at different life stages, namely, prenatal, post-weaning, puberty, and adult models. Based on typical behavioral assessments of autistic traits in the model mice, we established that ASD-like traits were induced in mice after PE feeding. In addition, we examined the induction of ASD-like traits in response to microplastic exposure using positron emission tomography, magnetic resonance spectroscopy, quantitative real-time polymerase chain reaction, microarray, and microbiome analysis. We believe these findings provide evidence in microplastics as a potential risk factor for ASD.

Correlation of ACE2 with RAS components after Losartan treatment in light of COVID-19.

Angiotensin-converting enzyme 2 (ACE2) is an important factor in coronavirus disease (COVID-19) interactions. Losartan (LOS) belongs to the angiotensin receptor blocker (ARB) family. Additionally, the protective role of ACE2 restored by LOS has been suggested and clinically examined in the treatment of COVID-19 patients. Furthermore, clinical trials with LOS have been conducted. However, the mechanism through which LOS enhances ACE2 expression remains unclear. In addition, the response of ACE2 to LOS differs among patients. Our LOS-treated patient data revealed a correlated mechanism of ACE2 with components of the renin-angiotensinogen system. We observed a significant positive regulation of MAS1 and ACE2 expression. In the context of LOS treatment of COVID-19, ACE2 expression could depend on LOS regulated MAS1. Thus, MAS1 expression could predict the COVID-19 treatment response of LOS.

Diacerein, an inhibitor of IL-1ß downstream mediated apoptosis, improves radioimmunotherapy in a mouse model of Burkitt's lymphoma.

Lymphoma has the characteristics of a solid tumor. Penetration of monoclonal antibodies is limited in solid tumors during radioimmunotherapy (RIT). Here, we first investigated the use of diacerein (DIA) as a combination drug to improve the penetration and therapeutic efficacy of 131I-rituximab (RTX) using the Burkitt's lymphoma mouse model. We selected DIA through computational drug repurposing and focused on rheumatoid arthritis (RA) drug interaction genes to minimize side effects. Then, the cytotoxicity of DIA was assessed in vitro using three different lymphoma cell lines. DIA-induced apoptosis was confirmed by Western blotting. After confirming apoptosis, we confirmed the enhanced uptake of 131I-RTX in Burkitt's lymphoma mouse model using SPECT/CT. Autoradiography of 131I-RTX confirmed the therapeutic effect of DIA. Finally, the tumor size and survival rate were assessed to measure the enhanced therapeutic efficacy when DIA was used. In addition, we assessed the dose-dependency of DIA in terms of the accumulation of 131I-RTX in tumor tissue, the tumor size, and the survival rate. The in vitro cytotoxicity was 10.9%. We showed that DIA induced apoptosis which was related to downstream IL-1ß signaling by Western blotting. We found increased Annexin V positive apoptosis after DIA administration. Immuno SPECT/CT images demonstrated a higher uptake of 131I-RTX in tumors in the DIA-administered group than that in the PBS-alone group. However, there were no statistical differences of dose-dependency between 20 mg/kg and 40 mg/kg of DIA. Tumor growth was significantly inhibited in the group treated with the combination of DIA plus 131I-RTX at 7 days after injection. Our suggested combination of DIA and 131I-RTX strategies could enhance the efficacy of 131I-RTX treatment.

Tumor treating fields can effectively overcome trastuzumab resistant breast cancer multiplication.

The Human Epidermal Growth Receptor 2, or the HER2 is one of the highest expressed negative receptor that constitutes approximately 15-20% of malevolent breast cancerous tumors among women. The prevalence of HER2 has untimely and unfavorable consequences on breast cancer, and its underlying carcinomous cell processes, structures, and growth. Trastuzumab (TRZ), a humanized antibody that is rooted in relatively recent foundations, has been found operational in its construction of treatments against HER2-positive breast cancer. This drug is combined with radiotherapy or chemotherapy to deregulate HER2 genes in the body. However, patients who suffer from evolved tumors in advanced stages of cancer exhibit a good amount of tolerance towards singularly used TRZ treatment. Inversely, the factorization of Tumor Testing Fields (TTFields or TTFs) into cancer therapy revives the functions of a TRZ treatment plan, by sensitizing the HER2 genes to the drug. In turn, this facilitates TRZ to continue limiting cancerous cell multiplication and toxicity levels within the treatment. This research evaluates the aspects and effects of this pairing, both in vivo and in vitro through BT474 cells. The TTFields conduct an electromagnetic boundary, which generates sine-wave radiations to manipulate the HER2 gene structure. The methods followed in the research also examines the gene cell cultures and their viability through solutions like Tryptophan blue, or the Crystal violet which may or may not deliver certain testmants to the experiment. The Western Blot Test and the IHC confirm the presence of antibodies and negative receptors in the BT474 cells. These procedures contribute to the formulation of a treatment plan that overcomes the TRZ-resistant nature of the tumor, which is essentially the aim of the research. Thus, the paper substantiates that a healthy combination of TTF's with TRZ can enhance the penetration of TRZ after inducing apoptosis due to TTFields therapy. The success of a TTField in undertaking this pursuit makes room for more utilization of it in future cancerous treatment ventures.

Relaxin-expressing oncolytic adenovirus induces remodeling of physical and immunological aspects of cold tumor to potentiate PD-1 blockade.

BACKGROUND: Currently, several antibody (Ab)-based therapies have shown excellent therapeutic effects in the clinic. Nonetheless, Ab penetration into tumor tissues is limited due to abnormal vasculature, tumor interstitial pressure, and excessive extracellular matrix (ECM) accumulation, thus demanding novel strategies to overcome these barriers. METHODS: The intratumoral distribution of therapeutic Abs were detected by fluorescence microscopy or positron emission tomography in both human gastric xenograft and syngeneic pancreatic hamster tumor models. The antitumor efficacy by combination of oncolytic adenovirus (Ad), which coexpresses relaxin (RLX), interleukin (IL)-12, and granulocyte macrophage colony-stimulating factor (GM-CSF) (oAd/IL12/GM-RLX) and antibody against the programmed cell death protein 1 (αPD-1) was examined in hamster subcutaneous and orthotopic pancreatic tumor models. The immunological aspects of these combination therapy regimen were assessed by flow cytometry or immunohistochemistry in subcutaneous hamster tumor models. RESULTS: Relaxin-expressing oncolytic Ad effectively degraded tumor ECM and enhanced the tumor penetration of trastuzumab in comparison with trastuzumab monotherapy. Based on these results, an oAd/IL12/GM-RLX was used to enhance the potency of immune checkpoint blockade. The combination of the oAd/IL12/GM-RLX and αPD-1 promoted a concomitant degradation of the tumor ECM and amelioration of the immunosuppressive tumor niches, ultimately enhanced intratumoral infiltration of both αPD-1 and activated T cells. Of note, the combination therapy was able to elicit a potent and durable antitumor immune response against cold tumors that were refractory to immune checkpoint inhibitor monotherapy. CONCLUSIONS: Our findings are the first to demonstrate that expression of four genes (IL-12p35, IL-12p40, GM-CSF, and RLX) mediated by a single oncolytic Ad vector can promote remodeling of both physical and immunological aspects of the tumor niches to overcome the major limitations of Ab-based therapies that have emerged in recent clinical trials.

Rapid and mass-producible synthesis of high-crystallinity MoSe2 nanosheets by ampoule-loaded chemical vapor deposition.

MoSe2 is an attractive transition-metal dichalcogenide with a two-dimensional layered structure and various attractive properties. Although MoSe2 is a promising negative electrode material for electrochemical applications, further investigation of MoSe2 has been limited, mainly by the lack of MoSe2 mass-production methods. Here, we report a rapid and ultra-high-yield synthesis method of obtaining MoSe2 nanosheets with high crystallinity and large grains by ampoule-loaded chemical vapor deposition. Application of high pressure to an ampoule-type quartz tube containing MoO3 and Se powders initiated rapid reactions that produced vertically oriented MoSe2 nanosheets with grain sizes of up to ∼100 µm and yields of ∼15 mg h-1. Spectroscopy and microscopy characterizations confirmed the high crystallinity of the obtained MoSe2 nanosheets. Transistors and lithium-ion battery cells fabricated with the synthesized MoSe2 nanosheets showed good performance, thereby further indicating their high quality. The proposed simple scalable synthesis method can pave the way for diverse electrical and electrochemical applications of MoSe2.

Inhibition of HIF-1α by Atorvastatin During 131I-RTX Therapy in Burkitt's Lymphoma Model.

BACKGROUNDS: Radioimmunotherapy (RIT) serves as a targeted therapy for non-Hodgkin lymphomas (NHL). Although HIF(Hypoxia-inducible factors)-1α is an important biomarker during radiation therapy, its role in NHL is unclear. Atorvastatin (ATV) is used as a combination drug for chemotherapy. METHODS: We investigated whether ATV downregulated tumor radio-resistance and enhanced the anticancer effect of 131I-RTX (rituximab) in Raji xenograft mouse models. First, the increased uptake and enhanced therapeutic effect of 131I-RTX by ATV was confirmed using molecular imaging in Raji xenograft subcutaneous model and orthotropic model with SPECT and IVIS images. Second, we examined the profile of differentially expressed miRNAs using miRNA array. RESULTS: We found that miR-346 inhibited HIF-1α/VEGF (Vascular endothelial growth factor) during ATV combination therapy with 131I-RTX. The underlying mechanism of ATV involved induction of anti-angiogenesis and radiosensitivity by downregulating HIF-1α in Raji cells. CONCLUSION: Our findings suggested that combination therapy with ATV and 131I-RTX is a promising strategy for enhancing the potency of 131I-RTX therapy in poorly responding patients and those with radio-resistance.