Combined Treatment Research Articles

19F MRI/CEUS Dual Imaging-Guided Sonodynamic Therapy Enhances Immune Checkpoint Blockade in Triple-Negative Breast Cancer.

Treatment of highly aggressive triple-negative breast cancer (TNBC) in the clinic is challenging. Here, a liposome nanodrug (LP@PFH@HMME) integrating imaging agents and therapeutic agents for bimodal imaging-guided sonodynamic therapy (SDT) is developed, which boosted immunogenicity to enable potent immunotherapy via immune checkpoint blockade (ICB) in TNBC. In the acidic tumor microenvironment (TME), LP@PFH@HMME undergoes "nano-to-micro" transformation due to a pH-responsive lipid fusion, which makes droplets much more sensitive to ultrasound (US) in contrast-enhanced ultrasound (CEUS) and SDT studies. The nanodrug demonstrates robust bimodal imaging ability through fluorine-19 magnetic resonance imaging (19F MRI) and CEUS bimodal imaging, and it exhibits excellent solubility in aqueous solution with relatively high 19F content and desirable long transverse relaxation time (T2 = 1.072 s), making it suitable for high-performance 19F MRI, in addition to effective accumulation of nanodrugs after tail vein injection. Thus, 19F MRI/CEUS dual imaging is achievable to show adequate time points for US irradiation of tumor sites to induce highly effective SDT, which produces abundant reactive oxygen species (ROS) triggering immunogenic cell death (ICD) to assist ICB-based immunotherapy. The combination treatment design of sonodynamic therapy with immunotherapy effectively inhibited TNBC growth and recurrence, highlighting the promise of multifunctional nanodrugs in treating TNBC.

TLR7 agonist, DSP-0509, with radiation combination therapy enhances anti-tumor activity and modulates T cell dependent immune activation

BackgroundTLR7 is a key player in the antiviral immunity. TLR7 signaling activates antigen-presenting cells including DCs and macrophages. This activation results in the adaptive immunity including T cells and B cells. Therefore, TLR7 is an important molecule of the immune system. Based on these observations, TLR7 agonists considered to become a therapy weaponize the immune system against cancer. Radiation therapy (RT) is one of the standard cancer therapies and is reported to modulate the tumor immune response. In this study, we aimed to investigate the anti-tumor activity in combination of TLR7 agonist, DSP-0509, with RT and underlying mechanism.ResultWe showed that anti-tumor activity is enhanced by combining RT with the TLR7 agonist DSP-0509 in the CT26, LM8, and 4T1 inoculated mice models. We found that once- weekly (q1w) dosing of DSP-0509 rather than biweekly (q2w) dosing is needed to achieve superior anti-tumor activities in CT26 model. Spleen cells from the mice in RT/DSP-0509 combination treatment group showed increased tumor lytic activity, inversely correlated with tumor volume, as measured by the chromium-release cytotoxicity assay. We also found the level of cytotoxic T lymphocytes (CTLs) increased in the spleens of completely cured mice. When the mice completely cured by combination therapy were re-challenged with CT26 cells, all mice rejected CT26 cells but accepted Renca cells. This rejection was not observed with CD8 depletion. Furthermore, levels of splenic effector memory CD8 T cells were increased in the combination therapy group. To explore the factors responsible for complete cure by combination therapy, we analyzed peripheral blood leukocytes (PBLs) mRNA from completely cured mice. We found that Havcr2low, Cd274low, Cd80high, and Il6low were a predictive signature for the complete response to combination therapy. An analysis of tumor-derived mRNA showed that combination of RT and DSP-0509 strongly increased the expression of anti-tumor effector molecules including Gzmb and Il12.ConclusionThese data suggest that TLR7 agonist, DSP-0509, can be a promising concomitant when used in combination with RT by upregulating CTLs activity and gene expression of effector molecules. This combination can be an expecting new radio-immunotherapeutic strategy in clinical trials.

The Effect of Napier Grass+Cowpea Intercropping and Different Fertilizer Levels on Soil Characteristics and Economics

Background: The field experiment was conducted to check the optimization of fertilizer requirement for napier grass and cowpea intercropping system at the farm of Lovely Professional University, Phagwara, Punjab during kharif season (2022). Methods: Three replications of factorial RBD design with 4 cropping patterns (I1, I2, I3 and I4) and 3 fertilizer levels (F1, F2 and F3) were set up. Study was conducted on total twelve treatment combinations, I1 (Sole napier with 100, 75 and 125% RDF), I2 (Sole Cowpea with 100, 75 and 125% RDF), I3 (Napier grass+cowpea intercropping in 1:2 ratio with 100, 75 and 125% RDF) and I4 (Napier grass+cowpea intercropping in 1:3 ratio with 100, 75 and 125% RDF). Result: The results showed that in the interaction effect of intercropping and fertilizer levels the the highest value of pH and EC was found to be in I1F2- Sole Napier+75% RDF (8.04 and 0.42 mhos cm-1, respectively). Higher OC was found in I4F3- Napier+cowpea (1:3)+125% RDF (18.23%) as compared to sole napier. However, sole cowpea plots recorded highest OC (18.60 %) in I2F3- Sole Cowpea+125% RDF but lowest pH and EC. The lowest N, Pand K in soil were seen in I1F2- Napier grass+75% RDF (90.00, 10.93 and 124.4 kg ha-1, respectively) in interaction of intercropping and fertilizer levels among treatment combinations of napier grass. I2F3- Sole cowpea+125% RDF recorded (225, 20.68 and 214.93 kg ha-1) N, P and K, respectively, which was highest among all the treatment combinations. Highest net returns and B: C ratio of 3.37 was recorded from intercropping ratio 1:3 and 125% RDF which was followed by 100% RDF (3.13) and 75% RDF (2.77).

Based on NF-κB and Notch1/Hes1 Signaling Pathways, the Mechanism of Artesunate on Inflammation in Osteoporosis in Ovariectomized Rats was Investigated.

Artesunate (ART) has the potential to modulate the nuclear factor kappa B (NF-κB) and Notch1/Hes1 signaling pathways, which play crucial roles in the pathogenesis of osteoporosis. This study aims to explore whether ART participates in the progression of osteoporosis by regulating these signaling pathways. In the in vitro experiments, we treated bone marrow mesenchymal stem cells (BMSCs) with different concentrations of ART (0, 3, 6, 12 µM) and evaluated osteogenic differentiation using alkaline phosphatase staining (ALP) and alizarin red S staining (ARS) staining. The expression levels of osteocalcin (OCN), RUNT-related transcription factor 2 (RUNX2), osteoprotegerin (OPG), and receptor activator of the nuclear factor kappa ligand (RANKL) were detected by real-time quantitative PCR (RT-qPCR). The effects of ART on NF-κB p65 and Notch1 protein expression were analyzed by Western blot (WB) and immunofluorescence (IF). In the in vivo experiments, a postmenopausal osteoporosis rat model was established via ovariectomy. Bone tissue pathological injury was evaluated using hematoxylin eosin (HE) staining. Serum ALP levels were measured using a kit, bone density was determined by dual-energy X-ray absorptiometry, and serum levels of bone gla protein (BGP), OPG, RANKL, tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and IL-1β were measured by enzyme-linked immunosorbent assay (ELISA). Additionally, the expression of NF-κB p65 and Notch1 in tissues was assessed by immunohistochemistry. In vitro experiments revealed that compared to the control group, ART dose-dependently promoted BMSCs proliferation and enhanced their osteogenic differentiation capability. The expression of OCN, RUNX2, and OPG significantly increased in the ART-treated group, while RANKL expression decreased significantly (p < 0.05). ART significantly inhibited the expression of NF-κB p65 and Notch1/Hes1 signaling pathway proteins (p < 0.05). Compared to ART treatment alone, combined treatment with ART and phorbol myristate acetate (PMA) or valproic acid (VPA) resulted in increased expression of NF-κB p65 and Notch1 proteins and decreased osteogenic differentiation capability (p < 0.05). In vivo experiments showed that in rats treated with ART, bone damage was significantly reduced, bone density and mineral content were restored considerably, and the expression of inflammatory factors (TNF-α, IL-6, IL-1β) decreased significantly (p < 0.05). Additionally, ART treatment significantly reduced the expression of NF-κB p65 and Notch1 proteins, increased OPG expression, and decreased BGP and RANKL levels (p < 0.05). In summary, ART facilitates the osteogenic differentiation of BMSCs by inhibiting the NF-κB and Notch1/Hes1 signaling pathways, thereby exerting significant protective effects against osteoporosis.

The combination of valsartan and spironolactone mitigated mitral regurgitation induced cardiac dysfunction in a novel rat model.

Despite its high prevalence, effective treatment for degenerative mitral regurgitation (MR) remains elusive. Although the mineralocorticoid-receptor antagonist spironolactone, in conjunction with renin-angiotensin system (RAS) inhibitors, has been shown to reduce mortality in patients with heart failure with reduced ejection fraction (HFrEF), its efficacy in managing degenerative MR is uncertain. In this study, we aimed to compare the effectiveness of valsartan (a renin-angiotensin system inhibitor), spironolactone, and combination therapy in mitigating MR-induced myocardial dysfunction. Using a mini-invasive model of degenerative MR, we administered valsartan (31 mg/kg/day), spironolactone (80 mg/kg/day), or a combination of both to rats over a 4-week period. Serial echocardiography and pressure-volume loops were utilized to assess cardiac function and hemodynamics. Rats with degenerative MR treated with valsartan or spironolactone alone did not show significant improvement in myocardial dysfunction. In contrast, combination therapy resulted in significant improvement. Similarly, the pressure-volume relationship was significantly improved in rats treated with the combination therapy compared to that in rats treated with a single therapy. Mechanistically, combination therapy effectively suppressed circulating and cardiac expression of aldosterone- and apoptosis-associated proteins. Overall, combination treatment with valsartan and spironolactone significantly attenuated the degenerative MR-induced myocardial stress and dysfunction, suggesting a potential therapeutic avenue for managing degenerative MR-induced HF.

Growth and Yield of Celery (Apium Graveolens L.) in Organic Cultivation on Alluvial Soil

Celery (Apium graveolens L.) is a horticultural crop that is consumable and offers numerous health benefits. The purpose of this study was to ascertain how celery growth and yield cultivated on alluvial soil were affected by the interaction between liquid organic NPK fertilizer and chicken manure. The study utilized a field experiment that was designed completely randomized comprising two factors. The first factor was the dosage of chicken manure with three levels: C1: 50 g/pot, C2: 100 g/pot, and C3: 150 g/pot. The second factor was liquid organic NPK fertilizer with three levels: L1: 1%, L2: 2%, and L3: 3%. All treatment combinations were performed in triplicates. The results indicated that the interaction between chicken manure and liquid organic NPK fertilizer significantly affected the number of tillers and dry weight of celery yield. Chicken manure as a single factor significantly influenced the number of stems and tillers. Liquid organic NPK fertilizer as a single factor significantly influenced the number of tillers, fresh weight, dry weight, and plant height. The combination of chicken manure and liquid organic NPK fertilizer (C1L3) produced the highest number of stems per clump (79.44 stems) and the highest number of tillers per clump (9.78 tillers). The combination of C2L3 yielded the highest fresh weight (184 g) and dry weight (17.33 g). Keywords: Alluvial soil, Celery, Chicken manure, Liquid organic NPK fertilizer

Pantothenate-encapsulated liposomes combined with exercise for effective inhibition of CRM1-mediated PKM2 translocation in Alzheimer's therapy

Alzheimer's disease (AD) is a complex neurodegenerative condition characterized by metabolic imbalances and neuroinflammation, posing a formidable challenge in medicine due to the lack of effective treatments. Despite considerable research efforts, a cure for AD remains elusive, with current therapies primarily focused on symptom management rather than addressing the disease's underlying causes. This study initially discerned, through Mendelian randomization analysis that elevating pantothenate levels significantly contributes to the prophylaxis of Alzheimer's disease. We explore the therapeutic potential of pantothenate encapsulated in liposomes (Pan@TRF@Liposome NPs), targeting the modulation of CRM1-mediated PKM2 nuclear translocation, a critical mechanism in AD pathology. Additionally, we investigate the synergistic effects of exercise, proposing a combined approach to AD treatment. Exercise-induced metabolic alterations share significant similarities with those associated with dementia, suggesting a potential complementary effect. The Pan@TRF@Liposome NPs exhibit notable biocompatibility, showing no liver or kidney toxicity in vivo, while demonstrating stability and effectiveness in modulating CRM1-mediated PKM2 nuclear translocation, thereby reducing neuroinflammation and neuronal apoptosis. The combined treatment of exercise and Pan@TRF@Liposome NP administration in an AD animal model leads to improved neurofunctional outcomes and cognitive performance. These findings highlight the nanoparticles' role as effective modulators of CRM1-mediated PKM2 nuclear translocation, with significant implications for mitigating neuroinflammation and neuronal apoptosis. Together with exercise, this dual-modality approach could offer new avenues for enhancing cognitive performance and neurofunctional outcomes in AD, marking a promising step forward in developing treatment strategies for this challenging disorder.

Clinical relevance of combined treatment with exercise in patients with chronic low back pain: a randomized controlled trial

Low back pain is a widespread public health concern owing to its high prevalence rates according to the Global Burden of Diseases. This study aimed to investigate the effect of exercise alone or in combination with manual therapy and kinesiotherapy on pain sensitivity, disability, kinesiophobia, self-efficacy, and catastrophizing in patients with chronic low back pain (CLBP). A total of 55 participants were enrolled and randomly allocated to one of three groups: (1) exercise alone group (ET; n = 19), (2) exercise + manual therapy group (ETManual therapy; n = 18), and (3) exercise + kinesio tape group (ETkinesiotape; n = 18). The interventions consisted of core stabilization exercises (ET group), prior spinal manipulation with core exercises (ETManual therapy group), and combined application of kinesiotape plus core stabilization exercises (ETkinesiotape group). The primary outcome was disability. The secondary outcomes were pain sensitization, kinesiophobia, catastrophizing, and self-efficacy. Assessments were performed at baseline and at weeks 3, 6, and 12. All therapies applied achieved significant improvements over time after 12 weeks in all parameters analyzed. ETmanualtherapy showed the greatest changes in all variables, with significant differences from the rest of the interventions in Oswestry (ODI) (3 and 6 weeks, respectively). A clinically significant cutoff point was achieved for the ETmanualtherapy group in the ODI parameter (−54.71%, −63.16% and −87.70% at 3, 6, and 12 weeks, respectively). Manual therapy prior to the core exercise technique was the most effective approach to improve health-related functionality compared with exercise alone or exercise combined with kinesiotape in patients with CLBP.Clinical Trial Registration Number: NCT05544890.

Mitoxantrone Combined with Engineered TRAIL-Nanovesicles for Enhanced Cancer Immunotherapy Via Converting Apoptosis into Pyroptosis.

Pyroptosis, a highly inflammatory form of programmed cell death, has emerged as a promising target for cancer immunotherapy. However, in the context of pyroptosis execution, while both caspase-3 and GSDME are essential, it is noteworthy that GSDME is frequently under-expressed in cold tumors. To overcome this limitation, engineered cellular nanovesicles (NVs) presenting TRAIL on their membranes (NVTRAIL) are developed to trigger the upregulation of cleaved caspase-3. When strategically combined with the chemotherapeutic agent mitoxantrone (MTO), known for its ability to enhance GSDME expression, MTO@NVTRAIL can convert cancer cells from apoptosis into pyroptosis, inhibit the tumor growth and metastasis successfully in primary tumor. The microparticles released by pyroptotic tumor cells also exhibited certain cytotoxicity against other tumor cells. In addition, tumor cells exposed to the combination treatment of MTO@NVTRAIL in vitro have also demonstrated potential utility as a novel form of vaccine for cancer immunotherapy. Flow analysis of the tumor microenvironment and draining lymph nodes reveals an increased proportion of matured dendritic cells and activation of T cells. In summary, the research provided a reference and alternative approach to induce cancer pyroptosis for clinical antitumor therapy based on engineered cellular nanovesicles and chemotherapy.

Nano-Selenium and Glutathione Enhance Cucumber Resistance to Botrytis cinerea by Promoting Jasmonic Acid-Mediated Cucurbitacin Biosynthesis.

Nano-selenium (Nano-Se), as a biological stimulant, promotes plant growth and development, as well as defense against biotic and abiotic stresses. Glutathione (GSH) is a crucial antioxidant and is also involved in the plant defense response to various stresses. In this study, the efficacy of combined treatment of Nano-Se and GSH (SeG) on the resistance of cucumber plants to Botrytis cinerea was investigated in terms of the plant phenotype, gene expression, and levels of accumulated metabolites using transcriptomic and metabolomic analyses. The exogenous application of SeG significantly enhanced plant growth and increased photosynthetic pigment contents and capacity. Notably, B. cinerea infection was reduced markedly by 41.9% after SeG treatment. At the molecular level, the SeG treatment activated the alpha-linolenic acid metabolic pathway and upregulated the expression of genes responsible for jasmonic acid (JA) synthesis, including LOX (210%), LOX4 (430%), AOS1 (100%), and AOC2 (120%), therefore promoting JA accumulation in cucumber. Intriguingly, the level of cucurbitacin, an important phytoalexin in cucurbitaceous plants, was found to be increased in SeG-treated cucumber plants, as was the expression of cucurbitacin biosynthesis-related genes OSC (107.5%), P450 (440.8%,31.6%), and ACT (414.0%). These genes were also upregulated by JA treatment, suggesting that JA may be an upstream regulator of cucurbitacin biosynthesis. Taken together, this study demonstrated that pretreatment of cucumber plants with SeG could activate the JA signaling pathway and promote cucurbitacin biosynthesis to enhance the resistance of the plants to B. cinerea infection. The findings also indicate that SeG is a promising biostimulant for protecting cucumber plants from B. cinerea infection without growth loss.

Prognostic significance of inflammatory markers in patients with advanced renal cell carcinoma receiving nivolumab plus ipilimumab.

A useful biomarker for the efficacy of immune checkpoint inhibitors (ICIs) in advanced renal cell carcinoma (RCC) has not yet been established. This study aims to investigate whether inflammatory markers are associated with the efficacy of nivolumab plus ipilimumab therapy before and during treatment. Data from patients with advanced clear cell RCC who received a combination treatment of nivolumab plus ipilimumab were retrospectively analyzed. The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) levels were assessed at baseline and 3, 6, and 9weeks after treatment initiation. The correlation between these inflammatory markers and the patient's prognosis was investigated. Eighty-four patients were identified. The multivariate analysis identified NLR at week 3, CRP at week 6, and NLR and CRP at week 9 as the consistent predictor associated with poor overall survival (OS) at each time point. The survival analysis and receiver operating characteristic (ROC) curve analysis revealed that an NLR of ≥ 2.4 at week 3, CRP of ≥ 1.4mg/dL at week 6, and NLR of ≥ 4.8 and CRP of ≥ 1.0mg/dL at week 9 were associated with worse OS (hazard ratios (HR) = 5.70, P = 0.008, HR = 3.23, P = 0.004, HR = 7.38, P < 0.001 and HR = 3.55, P = 0.002). Both NLR and CRP were considered useful biomarkers for understanding the prognosis during nivolumab plus ipilimumab therapy. Furthermore, an NLR of ≥ 4.8 and CRP of ≥ 1.0mg/dL at week 9 are helpful in reconsidering treatment continuation.

Is freeze-dried superfood kale supplementation healthier than common green peas? Outcomes of a cross-over trial.

Kale (Brassica oleracea species) is considered a functional food whose macronutrient and phytochemical contents are considered beneficial and widely considered as a superfood. In the present 6-week cross-over trial with a 2-week washout period, we compared the beneficial effects of freeze-dried kale over peas among Arab women with obesity. A total of 124 Saudi women with obesity were allocated to receive either freeze-dried kale (n = 62) or freeze-dried peas (n = 62) given in the form of 3-gram sachets thrice daily for 2 weeks, followed by a 2-week washout period and a cross-over of 4 weeks. Anthropometric measurements, glucose, lipids and markers of gut barrier function were assessed at baseline and post-intervention. Participants who took kale supplementation first resulted in significant weight reduction (p = 0.02) which was not observed among those who took peas first. Participants receiving pea supplementation first experienced a significant decline in Hba1c (p = 0.005) and CD14 (p = 0.03), but C-peptide increased (p = 0.05). Crossover analysis revealed significant carryover effects in most variables with non-significant combined treatment effects. Among the variables with no carryover effect with significant combined treatment effect include HbA1c which was in favor of the pea group (p = 0.005) and C-peptide which was modestly in favor of the kale group (p = 0.05). While both freeze dried kale and pea supplementation appear beneficial, supplementation of freeze-dried pea appears to be more effective in terms of acute glycemic control than kale. The study suggests that common but less-hyped vegetables such as pea maybe equally, if not more beneficial than the more expensive promoted superfoods such as kale. Longer clinical trials using a parallel design instead of cross-over are recommended to strengthen present findings.

Combinational therapy of mesenchymal stem cell-derived extracellular vesicles and azithromycin improves clinical and histopathological recovery in CLP sepsis model

BackgroundSepsis is a syndrome that occurs following an infection and marked by severe inflammatory responses, and if not treated in time, it can lead to multi-organ failure syndrome and death. This study examines the effects of a novel combination therapy using azithromycin and mesenchymal stem cell-derived extracellular vesicles (EVs) on a cecal ligation and puncture (CLP) model of sepsis. MethodsHuman Wharton’s jelly-mesenchymal stem cells were cultured, characterized, and used to extract EVs. The CLP sepsis model was induced in mice, followed by treatments: saline, AZM, EVs, and combination therapy (A+E). Clinical sepsis scores were recorded 24 h post-treatment. Serum, peritoneal fluid, and organ tissues (kidney, liver, lung) were collected and analyzed for biochemical parameters (AST ALT, and creatinine), inflammatory markers, bacterial load, and histopathological changes. ResultsThe A+E combined treatment improved the clinical scores of septic mice. The administration of A+E reduced bacterial loads in the peritoneum of septic mice, contributing to effective control of infection. Inflammatory markers of neutrophils-to-lymphocytes ratio (NLR) and TNF-α serum levels were significantly lower in the combinational therapy group, indicating significant anti-inflammatory effect of this combination. Additionally, combination of AZM and EVs alleviated organ damage mainly within liver, kidneys and lungs. Based on histopathological assessments and biochemical parameters, there was diminished tissue damage as well as reduced inflammation, which is correlated with improved functions of these vital organs. ConclusionThe combined use of azithromycin and EVs offers a promising therapeutic approach for sepsis by effectively controlling infection and modulating the inflammatory response.

Polyploidy and environmental stress response: a comparative study of fern gametophytes.

Climate change is rapidly altering natural habitats and generating complex patterns of environmental stress. Ferns are major components of many forest understories and, given their independent gametophyte generation, may experience unique pressures in emerging temperature and drought regimes. Polyploidy is widespread in ferns and may provide a selective advantage in these rapidly changing environments. This work aimed to understand whether the gametophytes of allopolyploid ferns respond differently to climate-related physiological stress than their diploid parents. The experimental approach involved a multifactorial design with 27 treatment combinations including exposure to multiple levels of drought and temperature over three treatment durations, with recovery measured at multiple timepoints. We measured Chl fluorescence from over 2000 gametophytes to evaluate stress avoidance and tolerance in diploid and polyploid species. Polyploids generally showed a greater ability to avoid and/or tolerate a range of stress conditions compared with their diploid counterparts, suggesting that polyploidy may confer enhanced flexibility and resilience under climate stress. Overall, these results suggest that polyploidy may provide some resilience to climate change in mixed ploidy populations. However, all species remain susceptible to the impacts of extreme drought and heat stress.

Optimizing Seed Priming Duration and Copper Levels for Coriander (Coriandrum sativum L.) Germination and Vigour

Background: An experiment was carried out in the STR Laboratory, Jawaharlal Nehru Krishi Vishwa Vidyalaya, Jabalpur, MP, during the Rabi season of 2022-2023 to determine the impact of seed priming time and copper levels on seed germination and vigour characteristics of the coriander seedlings. Method: The experiment was laid out in completely randomized design (CRD) with three replications and 12 treatment combinations of Copper levels (0, 300, 400 and 500ppm) and soaking duration (14, 16 and 18 h). Results: The outcomes demonstrated that priming treatments had a noteworthy impact on seedling germination and vigour traits. Significantly higher germination (82%), least mean germination time (7.9 days), maximum germination index (22.83), longest radicle (17.30 cm) and plumule length (13.09 cm), maximum vigour index-I (2374.05 cm) and vigour index-II (12.29 g) and lowest mortality rate (18%) was observed when seeds were primed with Cu @ 500 ppm soaking for 16 h. Success of crop production depends on quality of seeds and it’s germination percentage. Quality of seed susceptible to diverse climatic conditions resulting poor vigour and germination. Since availability of quality seed of coriander is very low, seed priming is an excellent technique which improves germination and better crop stand.

The therapeutic efficacy of 5-ALA based photodynamic therapy and chemotherapy combination in triple negative breast cancer cells

Triple negative breast cancer (TNBC) is one of the subtypes of breast cancer characterized by a heterogeneous and aggressive nature. Photodynamic therapy (PDT) has drawn significant attention in cancer treatment. However, solubility of photosensitizer, penetration problems into a target tissue and insufficient oxygen concentration limit the effectiveness of PDT. To overcome these limitations and to reduce the side effects of chemotherapy, combination treatment modalities play an essential role in cancer treatment. In this study, we aimed to investigate the combination efficacy of cisplatin-based chemotherapy and 5-Aminolevulinic acid (5-ALA)/PDT in TNBC cells and healthy breast cells in vitro. To determine the effect of the combination effects of cisplatin and 5-ALA/PDT on TNBC cells, two treatment protocols (simultaneous and sequential combination therapy) were evaluated compared with cisplatin and 5-ALA/PDT monotherapy and WST-1, Annexin V assay, acridine orange (AO) and mitochondrial staining were performed. Our findings showed that MDA-MB-231 TNBC cell viability was significantly decreased following simultaneous combination treatment compared to cisplatin and 5-ALA/PDT monotherapy. Additionally, simultaneous combination treatment was more effective than sequential combination treatment. The simultaneous combination treatment of 2.5 µM cisplatin and 5-ALA/PDT at 6 J/cm2 and 9 J/cm2 induced 46.78% and 53.6% total apoptotic death, respectively in TNBC cells compared with monotherapies (cisplatin (37.88%) and 5-ALA/PDT (6 J/cm2: 31.48% and 9 J/cm2: 37.78%). Additionally, cisplatin and 5-ALA/PDT combination treatment resulted in nuclear fragmentation and mitochondrial damage due to apoptosis. Our results suggest that cisplatin and 5-ALA/PDT simultaneous combination therapy could be a promising new alternative strategy for treating TNBC. However, further studies are required to assess the underlying molecular mechanisms of cisplatin and 5-ALA/PDT combination treatment at the molecular level.

NAD+ metabolic enzyme inhibitor as radiosensitizer for malignant meningioma and its modulation of P53 expression.

Surgical resection followed by radiotherapy (RT) is recommended for malignant meningioma but poor outcome is unavoidable. To improve the efficacy of RT in malignant meningioma, a targeted radiosensitizer could be added. Nicotinamide phosphoribosyltransferase (NAMPT), highly expressed in high-grade meningiomas may have a role in determining the radioresponse. Here, we evaluated the impact of NAMPT inhibition on radiosensitivity in malignant meningioma in vivo and in vitro. IOMM-Lee and TTMM705 cells were treated with NAMPT inhibition (FK866 or shRNA NAMPT) before irradiation. The subsequent clonogenic assay demonstrated significantly increased radiosensitivity. Combination treatment with FK866 and irradiation significantly increased the number of G2/M-phase cells, the percentage of apoptotic cells and the γ-H2A.X level compared to FK866 or RT alone. We examined the effect of NAMPT inhibition on NMI and p53 expression in IOMM-Lee and TTMM705 cells. NAMPT inhibition by FK866 and shRNA treatment increased NMI, p53, CDKN1A and BAX expression. Additionally, we assessed the efficacy of FK866/RT combination treatment in vivo. The combination treatment exhibited increased antitumor efficacy compared to either treatment alone. The Ki-67 level was significantly lower and the p53 and γ-H2A.X level was significantly higher in the combination treatment group than in any of the other three groups. In conclusion, these results indicate that FK866 improves radiosensitivity in malignant meningioma, an effect that may be attributed to the increase in p53 expression.

Synergistic effect of osthole and notopterol combination against Alzheimer's disease and osteoporosis by applying zebrafish AD/OP comorbidity model

Alzheimer's disease (AD) and osteoporosis (OP) are both serious degenerative diseases, with the potential for concurrent occurrence in clinical settings, and they share certain pathological correlations. Osthole (OST) and notopterol (NOT) are the main active ingredients in traditional Chinese medicine, Angelica pubescens and Notopterygium incisum, respectively, and they exhibit neuroprotective and osteoprotective effects. However, whether the combination of OST and NOT produces a synergistic effect against AD and/or OP remains unclear. The aim of this study was to investigate whether the combination of OST and NOT could produce synergistic anti-AD and/or OP effects using the previously constructed zebrafish AD/OP comorbidity model. Active compounds with anti-AD and OP effects were screened from Angelica pubescens and Notopterygium incisum through network pharmacology, identifying OST and NOT, respectively. Then, the AlCl3-induced (Aluminum chloride, AlCl3) AD combined with OP zebrafish model, in conjunction with the Chou-Talalay synergy evaluation model, was employed to assess whether the OST and NOT combination produced synergistic effects against AD and/or OP. Furthermore, a CuSO4-induced (Copper sulfate, CuSO4) inflammation zebrafish model was used to investigate whether the combination of OST and NOT produced synergistic anti-inflammatory effects, thereby resulting in synergistic anti-AD and/or OP effects. The results demonstrated that the OST-NOT combined treatment produced a synergistic anti-AD and OP effect. Moreover, the combined treatment of OST and NOT significantly inhibited nitric oxide (NO) and reactive oxygen species (ROS) release more effectively than OST or NOT alone, indicating a synergistic anti-inflammatory effect of the OST and NOT combined treatment.

Saline–Alkali Soil Reclamation Contributes to Soil Health Improvement in China

Soil salinization is a significant threat to soil health, especially to the agricultural ecosystem; it reduces vegetation biomass, destroys ecosystem diversity, and limits land use efficiency. This area of investigation has garnered extensive attention in China, especially in the arid and semi-arid areas, totaling 7.66 × 106 ha. A variety of theoretical research and technology developments have contributed to soil water and salt regulation and the screening of salt-tolerant varieties to improve nutrient utilization efficiency and microbial control and reduce ecological problems due to saline-based obstacles. These techniques can be classified into physical treatments, chemical treatments, biological treatments, and combined treatments; these different measures are all aimed at primarily solving saline–alkali stress. In general, the improvement and utilization of saline–alkali soil contribute to soil health improvement, concentrating on high-quality development, food security, ecological security, cultivated land protection, and agricultural upgrading. However, the risks of various technologies in the practical production process should be highlighted; green and healthy measures are still expected to be applied to saline–alkali land.

Extracorporeal Shock Wave Combined with Traditional Chinese Medicine Bone-setting Manipulation for External Humeral Epicondylitis: A Randomized Clinical Trial

Objective: The purpose of this study was to evaluate the clinical efficacy of extracorporeal shock waves combined with traditional Chinese medicine bone-setting manipulation for external humeral epicondylitis. Methods: Ninety-two patients with external humeral epicondylitis were randomly divided into an observation group and a control group. Patients in the control group were treated with extracorporeal shock waves while those in the observation group with traditional Chinese medicine bone-setting manipulation based on the control group. Patients in both groups were evaluated by the Visual Analogue Scale (VAS), Mayo Elbow Performance Score (MEPS), and Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH) before and after treatment. The inflammatory factors such as IL-6, IL-10, TNF-ɑ, and clinical outcomes were contrasted before and after treatment. Results: There were statistically significant differences in VAS score, MEPS score, and DASH score between the two groups before and after treatment (p &lt; 0.05). The observation group exhibited a more pronounced improvement in each score compared to the control group. Post-treatment, the inflammatory factors of both groups were significantly lower than pre-treatment levels (p &lt; 0.05), with the observation group showing a more noticeable decrease. The overall effectiveness of the observation group was higher than that of the control group, and the difference was statistically significant (p &lt; 0.05). Conclusion: The combination of extracorporeal shock wave therapy and traditional Chinese medicine bone-setting manipulation can effectively alleviate pain symptoms and improve dysfunction caused by external humeral epicondylitis, while also reducing inflammatory factor expression. This combined treatment may prove more effective than extracorporeal shock wave therapy alone. Clinical Trial: Registration: ChiCTR2200066075.