Synergistic Effect In Treatment Research Articles

Synergistic effect of bath-ultrasonication and heating treatments on two-steps treatment of brewers’ spent grain

The study aimed to evaluate the chemical composition, antioxidant activity and techno-functionality of brewers’ spent grain (BSG) treated with two-steps treatment involving 5, 15, and 25 min bath-ultrasonication (USB) continued with autoclave (AH) at 90, 110, and 130 °C and/or water-bath (CWH) at 80, 90, and 100 °C. The two-steps treatments slightly affected the water- and oil-holding capacity and extractable fat content. Most of the two-steps treatments increased the amount of flavan-3-ols and phenolic acids, up to 4 times higher compared to its control. The two-steps treatment involving CWH had no significant (p > 0.05) impact on fat content, antioxidants and techo-functionality of BSG. Up to 15 min USB increased the poly-unsaturated fatty acids and lowered the amount of saturated fatty acids. In conclusion, the two-steps treatment consists of USB (up to 15 min) continued with AH and CWH increased the amount of nutritional-related chemical composition such as UFA and phenolic acids as well as antioxidant activity of BSG.

The synergistic effect of Huangqi Gegen decoction on thrombosis relates to the astragalus polysaccharide-improved oral delivery of puerarin

Ethno-pharmacological relevanceHuangqi Gegen decoction (HGD), which comprises Astragali Radix (AR) and Puerariae Radix (PR), is widely used to treat thrombosis in China. However, the mechanism underlying its synergistic effect in thrombosis treatment remains unclear. Aim of the studyFollowing PR administration, low plasma exposure was reported for its primary ingredients. In this regard, this study examined the effect of AR on PR's antithrombotic efficacy with respect to the impact of Astragalus Polysaccharide (APS) on the oral delivery of Puerarin (PUE). Materials and methodsTo evaluate the synergistic effect of HGD, a thrombus mice model was established via intraperitoneal injection of carrageenan. After treatment, histopathological observations were made, and the proportion of thrombus length in the tail, as well as the plasma APTT, PT, INR, and FIB levels, were detected. Molecular docking was employed to assess the PR ingredients that could inhibit the HMGB1/NF-κB/NLRP3 pathway. The Pharmacokinetics of PR ingredients in rats were also compared between the PR and HGD groups. Moreover, the effect of APS on the solubility, intestinal absorption, and pharmacokinetics of PUE was evaluated. Furthermore, the impact of APS on the antithrombotic efficacy of PUE was assessed. ResultsIn mice, AR enhanced the antithrombotic effect of PR. This improved PR effect was associated with isoflavones-induced downregulation of the HMGB1/NF-κB/NLRP3 pathway. The synergistic effect resulting from the compatibility of HGD components was primarily achieved by improving the plasma exposure of PR isoflavones. Specifically, APS enhanced PUE's water solubility through the formation of self-assembly Nanoparticles, increasing its intestinal absorption and oral bioavailability, which, in turn, suppressed the HMGB1/NF-κB/NLRP3 pathway, thus improving its antithrombotic effect. ConclusionsOur findings revealed that APS improved PUE's plasma exposure, enhancing its inhibitory effect on the HMGB1/NF-κB/NLRP3 pathway. This mechanism presents a key aspect of the synergistic effect of HGD compatibility in thrombosis treatment.

Multi-modal triggered-release sonodynamic/chemo/phototherapy synergistic nanocarriers for the treatment of colon cancer.

Most colon cancer patients are diagnosed at an advanced stage, with a grim prognosis. In clinical, various combination therapies have been employed to enhance the efficacy of colon cancer treatment. The essence of combined treatment is the judicious selection and combination of various treatment units. Phototherapy (PT), sonodynamic therapy (SDT), and chemotherapy are treatment modalities that rely on the active molecules to treat tumors, and have been demonstrated to synergistically enhance tumor treatment efficacy. However, the differences in the metabolism of active molecules and hypoxic microenvironment of tumors have limited the synergistic effects of the aforementioned methods. To address this significant issue, in this study, we utilized polydopamine (PDA) as the encapsulated material to form a rigid shell that contains the therapeutic molecules IR-780 and methotrexate (MTX) on the surface of perfluorohexane (PFH) microdroplets through self-assembling method to develop an SDT/chemotherapy/PT combined nanoparticles (SCP NPs). Transmission electron microscopy (TEM) revealed that the nanoparticles exhibited a hollow shell structure, with an average size of approximately 100nm. SCP NPs have excellent stability and biocompatibility in both in vitro and in vivo. The absorption and emission spectrum of the loaded IR-780 did not exhibit any significant shift, and the photothermal temperature rose to 92°C. Their ultrasonic cavitation effect was good and their cell inhibitory effect of MTX was maintained. SCP NPs can achieve multi-modal triggered release through ultrasound, laser irradiation, and pH, ensuring a simultaneous accumulation of therapeutic molecules in the tumor area and effectively alleviating tumor hypoxia. Additionally, both the near-infrared fluorescence (NIF) signal and the ultrasonic cavitation signal of the nanoparticles can be utilized for tracking and monitoring treatment efficacy. Most notably, SCP NPs exhibited outstanding synergistic treatment effects at low intervention levels, resulting in a 67% cure rate of tumors. These results provide an experimental basis for developing the new clinical treatments for colon cancer.

Induction of Cell Death by Bifidobacterium infantis DS1685 in Colorectal and Breast Cancers via SMAD4/TGF-Beta Activation.

Therapeutic advancements in treatments for cancer, a leading cause of mortality worldwide, have lagged behind the increasing incidence of this disease. There is a growing interest in multifaceted approaches for cancer treatment, such as chemotherapy, targeted therapy, and immunotherapy, but due to their low efficacy and severe side effects, there is a need for the development of new cancer therapies. Recently, the human microbiome, which is comprised of various microorganisms, has emerged as an important research field due to its potential impact on cancer treatment. Among these microorganisms, Bifidobacterium infantis has been shown to significantly improve the efficacy of various anticancer drugs. However, research on the role of B. infantis in cancer treatment remains insufficient. Thus, in this study, we explored the anticancer effect of treatment with B. infantis DS1685 supernatant (BI sup) in colorectal and breast cancer cell lines. Treatment with BI sup induced SMAD4 expression to suppress cell growth in colon and breast cancer cells. Furthermore, a decrease in tumor cohesion was observed through the disruption of the regulation of EMT-related genes by BI sup in 3D spheroid models. Based on these findings, we anticipate that BI sup could play an adjunctive role in cancer therapy, and future cotreatment of BI sup with various anticancer drugs may lead to synergistic effects in cancer treatment.

Inter-crosslinked spirocyclic mixed matrix membranes exhibiting enhanced gas permeability, selectivity, and plasticization resistance

Poor interfacial compatibility is the most common issue inhibiting performance enhancement in mixed matrix membranes (MMM) for gas and liquid separations. To address this issue, we fabricated highly selective and permeable inter-crosslinked mixed matrix membranes (IcMMMs) based on carboxylic-acid functionalized polymer of intrinsic microporosity-1 (CPIM) containing up to 30 wt % triptycene-isatin polymer porous network (PPN) particles. Polymer-filler inter-crosslinking is accomplished via thermal decarboxylation at 200 °C, which is the lowest temperature this reaction has been found to occur in the literature. This low temperature circumvents potential issues with degradation of porous supports or gutter layer materials, and thus enables these materials to be integrated into traditional membrane processes. The resulting IcMMMs exhibit gel fractions above 90 %. Beyond IcMMMs, membranes based on neat CPIM, thermally crosslinked CPIM, as well as non-crosslinked CPIM-PPN mixed matrix membranes were fabricated to elucidate the individual and synergistic effects of filler inclusion and thermal treatment. In addition to showing upper bound permeability-selectivity performance, IcMMMs also exhibit an almost unprecedented stability against plasticization upon extended exposure to CO2 up to 50 atm or above. This study shows that crosslinking across the polymer-filler interface is the key feature to achieve simultaneous enhancement in permeability, selectivity, and stability. To elucidate the molecular mechanism of these enhancements in the IcMMMs with respect to the baseline materials, permeability was broken into its sorption and diffusion contributions and an energetic analysis of sorption was performed. The low cost of PPNs coupled with the mild crosslinking temperature make this approach highly scalable, resulting in materials exhibiting high rigidity and structural stability with the potential to excel in aggressive separations, such as organic solvent separations or high-CO2 content, high-pressure natural gas sweetening.

Polydopamine-Based Nanoparticles for Synergistic Chemotherapy of Prostate Cancer.

Immune regulatory small molecule JQ1 can block its downstream effector PD-L1 pathway and effectively reverse the PD-L1 upregulation induced by doxorubicin (DOX). So the synergistic administration of chemotherapeutic drug DOX and JQ1 is expected to increase the sensitivity of tumors to immune checkpoint therapy and jointly enhance the body's own immunity, thus effectively killing tumor cells. Therefore, a drug delivery system loaded with DOX and JQ1 was devised in this study. Polydopamine nanoparticles (PDA NPs) were synthesized through spontaneous polymerization. Under appropriate pH conditions, DOX and JQ1 were loaded onto the surface of PDA NPs, and the release of DOX and JQ1 were measured using UV-Vis or high performance liquid chromatography (HPLC). The mechanism of fabricated nanocomplex in vitro was investigated by cell uptake experiment, cell viability assays, apoptosis assays, and Western blot analysis. Finally, the tumor-bearing mouse model was used to evaluate the tumor-inhibiting efficacy and the biosafety in vivo. JQ1 and DOX were successfully loaded onto PDA NPs. PDA-DOX/JQ1 NPs inhibited the growth of prostate cancer cells, reduced the expression of apoptosis related proteins and induced apoptosis in vitro. The in vivo biodistribution indicated that PDA-DOX/JQ1 NPs could accumulated at the tumor sites through the EPR effect. In tumor-bearing mice, JQ1 delivered with PDA-DOX/JQ1 NPs reduced PD-L1 expression at tumor sites, generating significant tumor suppression. Furthermore, PDA-DOX/JQ1 NPs could reduce the side effects, and produce good synergistic treatment effect in vivo. We have successfully prepared a multifunctional platform forsynergistic prostate cancer therapy.

Structural degradation of polyallyl diglycol carbonate (PADC) polymer: analytical characterization and simulation studies

A comprehensive study has been carried out to understand the details of structural modifications of polyallyl diglycol carbonate (PADC) polymer under the effects of different external factors. Synergistic effect of heat treatment with radiation on the polymer structure was studied. Incorporation of a neutral chromophore to understand the structural changes was attempted. Theoretical simulations were applied to get insight into the detailed aspects of structural modifications. Diverse techniques were used to characterize the samples and compare with the results of simulation studies.

Synergistic effect of solvent addition and temperature treatment on conductivity enhancement of MWCNTs: PEDOT:PSS composite ink for electrodes in all printed solid-state micro-supercapacitors

All solid-state micro-supercapacitors (S-MSCs) are pivotal for modern wearables as they offer rapid energy storage and release, with seamless integration into small, lightweight wearables. Developing all printed S-MSCs is a cost-effective alternative to traditional S-MSCs and can potentially revolutionize wearable energy storage technologies. This manuscript presents an innovative, substrate-friendly approach to enhance the conductivity and electrochemical performance of screen-printed electrodes for S-MSCs using multi-walled carbon nanotubes (MWCNTs): PEDOT:PSS (poly(3,4-ethylene dioxythiophene): poly(styrene sulfonate)) composite ink. By incorporating various polar solvents into the ink formulation and optimizing printing and drying parameters, a four-fold increase in conductivity (5.5 × 103 S/m) was achieved. The synergy of polar solvent addition and temperature treatment on the dielectric screening, preferential solvation, and partial segregation of PSS were identified as the principal reason behind this enhancement. The optimally formulated ink was employed to create supercapacitor electrodes, demonstrating hybrid capacitive behavior with both liquid and gel electrolytes. An impressive 97.5 % decrease in charge transfer resistance (RCT) and a corresponding increase in areal capacitance and energy density were observed for these supercapacitors due to the segregation of PEDOT and PSS achieved by the synergistic effect. All printed S-MSCs were also fabricated with an impressive areal capacitance of 9.82 mF/cm2 @ 60 µA/cm2 and areal energy density of 1.964 µWh/cm2 at an areal power density of 63 µW/cm2. The fabricated S-MSCs exhibited impeccable capacitance retention of 99.7 % after 6,000 operation cycles and impressive stability upto 10,000 bending cycles, making them promising energy storage solutions for flexible and wearable devices.

Novel composite fatty acid vesicles-in-Pluronic lecithin organogels for enhanced magnolol delivery in skin cancer treatment

A novel composite carrier composed of Pluronic lecithin organogels and fatty acid vesicles was used to enhance the stability and facilitate the topical delivery of a natural bioactive drug, magnolol (Mag), for treatment of skin cancer. Jojoba oil was incorporated in the organogel (OG) base to provide a synergistic effect in treatment of skin cancer. The organoleptic properties, rheological behavior, morphology, and drug content of the OG formulations were investigated with emphasis on the impact of vesicle loading on the OG characteristics. The effect of OG on Mag release and ex-vivo permeation studies were evaluated and compared to free Mag in OG. The biological anti-tumor activity of the OG formulae was assessed using a skin cancer model in mice.All OG formulations exhibited uniform drug distribution with drug content ranging from 92.22 ± 0.91 to 100.45 ± 0.77 %. Rheological studies confirmed the OG shear-thinning flow behavior. Ex-vivo permeation studies demonstrated that the permeation of Mag from all OG formulations surpassed that obtained with free Mag in the OG. The anti-tumor activity studies revealed the superior efficacy of 10-hydroxy-decanoic acid (HDA)-based vesicles incorporated in OG formulations in mitigating 7,12- dimethylbenz(a)anthracene (DMBA)-induced skin cancer, thereby offering a promising platform for the local delivery of Mag.

Mechanism and bioinformatics analysis of the effect of berberine-enhanced fluconazole against drug-resistant Candida albicans

Biofilms produced by Candida albicans present a challenge in treatment with antifungal drug. Enhancing the sensitivity to fluconazole (FLC) is a reasonable method for treating FLC-resistant species. Moreover, several lines of evidence have demonstrated that berberine (BBR) can have antimicrobial effects. The aim of this study was to clarify the underlying mechanism of these effects. We conducted a comparative study of the inhibition of FLC-resistant strain growth by FLC treatment alone, BBR treatment alone, and the synergistic effect of combined FLC and BBR treatment. Twenty-four isolated strains showed distinct biofilm formation capabilities. The antifungal effect of combined FLC and BBR treatment in terms of the growth and biofilm formation of Candida albicans species was determined via checkerboard, time-kill, and fluorescence microscopy assays. The synergistic effect of BBR and FLC downregulated the expression of the efflux pump genes CDR1 and MDR, the hyphal gene HWP1, and the adhesion gene ALS3; however, the gene expression of the transcriptional repressor TUP1 was upregulated following treatment with this drug combination. Furthermore, the addition of BBR led to a marked reduction in cell surface hydrophobicity. To identify resistance-related genes and virulence factors through genome-wide sequencing analysis, we investigated the inhibition of related resistance gene expression by the combination of BBR and FLC, as well as the associated signaling pathways and metabolic pathways. The KEGG metabolic map showed that the metabolic genes in this strain are mainly involved in amino acid and carbon metabolism. The metabolic pathway map showed that several ergosterol (ERG) genes were involved in the synthesis of cell membrane sterols, which may be related to drug resistance. In this study, BBR + FLC combination treatment upregulated the expression of the ERG1, ERG3, ERG4, ERG5, ERG24, and ERG25 genes and downregulated the expression of the ERG6 and ERG9 genes compared with fluconazole treatment alone (p < 0.05).

Integrated oral microgel system ameliorates renal fibrosis by hitchhiking co-delivery and targeted gut flora modulation

BackgroundRenal fibrosis is a progressive process associated with chronic kidney disease (CKD), contributing to impaired kidney function. Active constituents in traditional Chinese herbs, such as emodin (EMO) and asiatic acid (AA), exhibit potent anti-fibrotic properties. However, the oral administration of EMO and AA results in low bioavailability and limited kidney accumulation. Additionally, while oral probiotics have been accepted for CKD treatment through gut microbiota modulation, a significant challenge lies in ensuring their viability upon administration. Therefore, our study aims to address both renal fibrosis and gut microbiota imbalance through innovative co-delivery strategies.ResultsIn this study, we developed yeast cell wall particles (YCWPs) encapsulating EMO and AA self-assembled nanoparticles (NPYs) and embedded them, along with Lactobacillus casei Zhang, in chitosan/sodium alginate (CS/SA) microgels. The developed microgels showed significant controlled release properties for the loaded NPYs and prolonged the retention time of Lactobacillus casei Zhang (L. casei Zhang) in the intestine. Furthermore, in vivo biodistribution showed that the microgel-carried NPYs significantly accumulated in the obstructed kidneys of rats, thereby substantially increasing the accumulation of EMO and AA in the impaired kidneys. More importantly, through hitchhiking delivery based on yeast cell wall and positive modulation of gut microbiota, our microgels with this synergistic strategy of therapeutic and modulatory interactions could regulate the TGF-β/Smad signaling pathway and thus effectively ameliorate renal fibrosis in unilateral ureteral obstruction (UUO) rats.ConclusionIn conclusion, our work provides a new strategy for the treatment of renal fibrosis based on hitchhiking co-delivery of nanodrugs and probiotics to achieve synergistic effects of disease treatment and targeted gut flora modulation.Graphical

Synergistic effects of plasma-activated water (PAW) and electrochemical treatment on the color of tuna slices

Recent advances in the field of meat processing have promoted the exploration of innovative methods to enhance the visual appeal of meat products. This research introduces a new approach that involves the combination of plasma-activated water (PAW) and electrochemical processes to improve the redness of tuna meat. The study revealed that subjecting PAW to electrochemical treatment at −0.85 V for 5 min significantly enhanced its color-enhancing properties. This enhancement is linked to the conversion of nitrites and nitrates into nitric oxide (NO) during the electrochemical process, which then interact with myoglobin to form nitrosomyoglobin (NOMb), resulting in the desired pink coloration. While a slight rise in residual nitrite and lipid oxidation was noted after treatment, these levels remained within acceptable limits according to prevailing safety standards, ensuring consumer safety. This study sets the stage for the potential utilization of a combined approach involving PAW and electrochemical methods in meat processing, offering the prospect of developing more appealing and commercially viable meat products.

Blocking the angiopoietin-2-dependent integrin β-1 signaling axis abrogates small cell lung cancer invasion and metastasis.

Small cell lung cancer (SCLC) is the most aggressive lung cancer entity with an extremely limited therapeutic outcome. Most patients are diagnosed at an extensive stage. However, the molecular mechanisms driving SCLC invasion and metastasis remain largely elusive. We used an autochthonous SCLC mouse model and matched samples from patients with primary and metastatic SCLC to investigate the molecular characteristics of tumor metastasis. We demonstrate that tumor cell invasion and liver metastasis in SCLC are triggered by an Angiopoietin-2 (ANG-2)/Integrin β-1-dependent pathway in tumor cells, mediated by focal adhesion kinase/Src kinase signaling. Strikingly, CRISPR-Cas9 KO of Integrin β-1 or blocking Integrin β-1 signaling by an anti-ANG-2 treatment abrogates liver metastasis formation in vivo. Interestingly, analysis of a unique collection of matched samples from patients with primary and metastatic SCLC confirmed a strong increase of Integrin β-1 in liver metastasis in comparison with the primary tumor. We further show that ANG-2 blockade combined with PD-1-targeted by anti-PD-1 treatment displays synergistic treatment effects in SCLC. Together, our data demonstrate a fundamental role of ANG-2/Integrin β-1 signaling in SCLC cells for tumor cell invasion and liver metastasis and provide a potentially new effective treatment strategy for patients with SCLC.

Improved implicit self-esteem is associated with extended antidepressant effects following a novel synergistic intervention.

In a previously published randomized controlled trial, automated self-association training (ASAT), a novel digital intervention, was found to extend the rapid antidepressant effect of a single infusion of ketamine for at least 30 days. In this secondary analysis, we aimed to understand the potential role of implicit self-esteem in the combined antidepressant effect of ketamine and ASAT training, by investigating the novel synergistic treatment's effects on implicit self-associations and their relation to symptom improvement. A total of 154 adults (ages 18-60) with treatment-resistant unipolar depression and lower-than-normative explicit self-esteem were randomized in a double-blind, parallel-arm design to receive one of three treatment allocations: an active/active treatment combination consisting of one infusion of ketamine (0.5 mg/kg) followed by four days of ASAT ( ~ 30-40 min/day), or one of two control arms that lacked either the active drug or the active behavioral component. The Implicit Association Test (IAT) was used to behaviorally assess the strength of association between self-related stimuli and negative concepts. Linear regression models were used to test the relationship between group assignment, IAT scores acquired immediately post-treatment, and both acute and extended clinical outcomes (% change in Montgomery-Asberg Depression Rating Scale scores, relative to pre-treatment baseline) in the trial. The group assigned to ketamine + ASAT intervention, compared to the other groups, had a pattern of IAT scores indicating more positive self-associations immediately after treatment relative to the control arms (F(1, 131) = 3.979; p = 0.048). In regression models, IAT scores tracked with concurrent (acute post-treatment) % change in MADRS scores across all treatment arms (p = 0.001), and mediated more extended (Day 30) depression improvements specifically for the ketamine+ASAT arm (group * IAT interaction term: β = -0.201; p = 0.049). Our findings suggest that changing implicit self-worth during a post-ketamine 'plasticity window' is one key mechanism whereby the novel ketamine+ASAT treatment combination exerts its antidepressant benefit, confirming the intended treatment target at the level of implicit cognition. Future studies should seek to further enhance the reliability of the biobehavioral intervention's impact on implicit cognition, as this mechanism appears linked to the intervention's enduring clinical benefits.

Combined effects of cadmium and sulfamethoxazole on Eisenia fetida: Insights into accumulation, subcellular partitioning, biomarkers and toxicological responses

Cadmium (Cd) and sulfamethoxazole (SMX) frequently coexist in farmlands, yet their synergistic toxicological impacts on terrestrial invertebrates remain unexplored. In this study, earthworms were exposed to artificial soils percolated with Cd (5 mg/kg), SMX (5 mg/kg) or combination of them for 7 days, followed by a 12-day elimination phase in uncontaminated soil. The uptake of Cd and SMX by the earthworms, along with their subcellular distribution, was meticulously analyzed. Additionally, a suite of biomarkers—including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and weight loss—were evaluated to assess the health status of the earthworms and the toxicological effects of the Cd and SMX mixture. Notably, the cotreatment with Cd and SMX resulted in a significantly higher weight loss in Eisenia fetida (41.25 %) compared to exposure to Cd alone (26.84 %). Moreover, the cotreatment group exhibited substantially higher concentrations of Cd in the total internal body, fraction C (cytosol), and fraction E (tissue fragments and cell membranes) in Eisenia fetida compared to Cd alone counterparts. The combined exposure also significantly elevated the SMX levels in the total body and fraction C compared with the SMX-only treated earthworms. Additionally, Eisenia fetida subjected to the combined treatment showed markedly increased activities of SOD, CAT, and MDA compared to those treated with Cd alone. The effect addition indices (EAIs), ranging from 1.00 to 2.23, unequivocally demonstrated a synergistic effect of the combined treatments. Interestingly, relocating the earthworms to clean soil did not mitigate the observed adverse effects. These findings underscore the increased risk posed by the Cd-SMX complex to terrestrial invertebrates in agricultural areas.

Biosensor-Based Assessment of Pesticides and Mineral Fertilizers’ Influence on Ecotoxicological Parameters of Soils under Soya, Sunflower and Wheat

Pesticides and fertilizers used in agriculture can negatively affect the soil, increasing its toxicity. In this work, a battery of whole-cell bacterial lux-biosensors based on the E. coli MG1655 strain with various inducible promoters, as well as the natural luminous Vibrio aquamarinus VKPM B-11245 strain, were used to assess the effects of agrochemical soil treatments. The advantages of using biosensors are sensitivity, specificity, low cost of analysis, and the ability to assess the total effect of toxicants on a living cell and the type of their toxic effect. Using the V. aquamarinus VKPM B-11245 strain, the synergistic effect of combined soil treatment with pesticides and mineral fertilizers was shown, which led to an increase in the overall (integral) toxicity of soils higher than that of the individual application of substances. Several probable implementation mechanisms of agrochemical toxic effects have been discovered. DNA damage caused by both SOS response induction and alkylation, oxidative stress due to increased superoxide levels, and damage to cellular proteins and membranes are among them. Thus, the usage of biosensors makes it possible to assess the cumulative effect of various toxicants on living organisms without using expensive chemical analyses.

Fractional CO2 laser, platelet rich plasma and combination of both in treatment of female pattern hair loss

Background Female pattern hair loss (FPHL) is one of the most common chronic problems seen by dermatologists worldwide. Hair loss has a significant influence on the quality of life and is associated with low self-esteem and depression. The treatment modalities vary from medical approaches to surgical interventions. However, limited perceived efficacy of a therapeutic regimen may lead to premature stoppage of treatment. Objective To evaluate the efficacy of platelet rich plasma (PRP), fractional CO2 laser and combination of both in treatment of FPHL. Patients and methods This is a split-scalp prospective interventional study in which thirty patients presenting with FPHL received PRP in one area, fractional CO2 in another one, combined fractional CO2 and PRP in a third one and saline intradermal injection in the fourth area in frontal and mid scalp region of scalp. The sessions were scheduled every 2 weeks for 4 sessions, then monthly for 2 months. Patients were evaluated after each session and 3months after the last session. The results were evaluated by trichoscopic and folliscopic examination in the four examined areas. Assessment of treatment response was done according to the count of terminal and vellus hair, the thickness and density of hair shafts and the percentage of change, determined by folliscopic examination. Patients’ satisfaction and side effects were evaluated. Results There was significant difference between the studied groups as regards percentage of change of terminal hair, vellus hair, hair thickness and hair density after treatment. Pairwise comparisons showed that the combined group was statistically better than either PRP, fractional CO2, or saline group as regards all studied parameters (P value was &lt;0.05 for each). Conclusion Combination of fractional CO2 laser and topical PRP application would have a synergistic effect in treatment of FPHL. The technique would be an excellent alternative to injections in order to stimulate hair growth in patients with FPHL.

Structural insights on anti-biofilm mechanism of heated slightly acidic electrolyzed water technology against multi-resistant Staphylococcus aureus biofilm on food contact surface

Slightly acidic electrolyzed water (SAEW) has proven to be an efficient and novel sanitizer in food and agriculture field. This study assessed the efficacy of SAEW (30 mg/L) at 40 °C on the inactivation of foodborne pathogens and detachment of multi-resistant Staphylococcus aureus (MRSA) biofilm. Furthermore, the underlying mechanism of MRSA biofilm under heated SAEW at 40 °C treatment on metabolic profiles was investigated. The results showed that the heated SAEW at 40 °C significantly effectively against foodborne pathogens of 1.96–7.56 (lg (CFU/g)) reduction in pork, chicken, spinach, and lettuce. The heated SAEW at 40 °C treatment significantly reduced MRSA biofilm cells by 2.41 (lg (CFU/cm2)). The synergistic effect of SAEW treatment showed intense anti-biofilm activity in decreasing cell density and impairing biofilm cell membranes. Global metabolic response of MRSA biofilms, treated by SAEW at 40 °C, revealed the alterations of intracellular metabolites, including amino acids, organic acid, fatty acid, and lipid. Moreover, signaling pathways involved in amino acid metabolism, energy metabolism, nucleotide synthesis, carbohydrate metabolites, and lipid biosynthesis were functionally disrupted by the SAEW at 40 °C treatment. As per our knowledge, this is the first research to uncover the potential mechanism of heated SAEW treatment against MRSA biofilm on food contact surface.

SH003 Enhances the Anti-cancer Effects of Dabrafenib on Lung Cancer Harboring BRAF G469A Mutation by Inhibiting the MAPK Signaling Pathway.

BRAF mutations are relatively uncommon in lung cancer. However, the majority of therapies targeting BRAF mutations have been developed exclusively for lung cancer patients with V600E mutations, limiting their effectiveness in treating tumors with the non-V600E BRAF mutations. As a result, there is a need to explore effective therapeutic strategies for patients with lung cancer carrying non-V600 BRAF mutations. Therefore, this study aims to identify a combination treatment approach that effectively targets lung cancer with G469A non-V600 BRAF alteration. The efficacy of drug treatments was assayed using a patient-derived xenograft (PDX) mouse model. Histological analysis was performed using hematoxylin and eosin and immunohistochemical staining. Cell viability and growth were determined using the WST-8 and colony formation assays. Protein levels and apoptosis were analyzed using western blot and flow cytometry, respectively. We demonstrated that the lung cancer cells harboring the non-V600E G469A mutation were responsive to the combination of SH003 and dabrafenib. By utilizing patient-derived xenograft (PDX) models, we identified that this combined treatment induces apoptosis and exhibits antitumor effects through the reduction of ERK signals. The synergistic effect of the combination treatment on BRAF G469A lung cancer cells was consistent with its effects on PDX models, suggesting that the molecular mechanism of apoptosis involves a decrease in the MEK/ERK signaling pathway. The SH003 and dabrafenib combination can be potentially developed as an effective treatment strategy for addressing lung cancer patients with the BRAF G469A mutation.

Investigation on high cycle fatigue performance of additively manufactured Alloys: Synergistic effects of surface finishing and Post-Heat treatment

The high-cycle fatigue (HCF) behavior of additively manufactured (AM) materials in structural applications remains insufficiently explored when contrasted with conventionally fabricated alloys. Addressing this research gap, we systematically investigate the potential to enhance HCF performance in AM alloys through a strategic interplay of surface finishing and post-heat treatment design. Concentrating on laser powder bed fusion, we evaluate surface roughness and post-heat treatment effects on HCF life across a300to1000 MPa stress range. Findings show that, at700to1000 MPa, surface finishing significantly extends HCF life by mitigating crack initiation. Paradoxically, at300to700 MPa, it shortens HCF life due to induced local residual stress on the sample surface. Additionally, post-aging finishing moderately enhances HCF life compared to pre-aging. This underscores the crucial role of sequence in surface finishing and heat treatment, emphasizing their collective impact on fatigue properties. Our study advances the understanding of post-processing factors influencing AM alloy fatigue properties, providing valuable insights for enhancing mechanical performance.