Additive Effects Research Articles

Biological Activities and Mechanisms of Actions of Bioactive Compounds (BACS) Identified in Pure and Ternary Blends of Cocoyam, Soya Bean and Bambara Groundnut Flour Using Gas Chromatography-Mass Spectrometry (GC-MS) Technique: A Review

Background: functional foods contain bioactive compounds (BACS) and can be sourced from both animals and plants like cocoyam (CY), soya bean (SB) and bambara groundnut (BGN). previous studies have reported various bacs in each of these plants but literature is scanty on the types and amount, of bacs in such flour blends and formulations. when in combinations as blend, anti-oxidant, interactions occur, resulting in either potentiation, additive, synergistic or antagonistic effect, depending on several various variables. their in-vivo bioactivities which are due to various structural features of the BACS, can be antioxidant, anti-inflammatory, hypocholestrolaemic, antimicrobial and anti-diabetic activities. in this review the various bacs identified by gas chromotagraphy (GC)-mass spectrometry (MS) technique in the various formulations of CY-SB-BGN flour blends were researched for their biological activities and reported mechanisms of actions. Methodology: a google search of a study on bacs identified using gc-ms in cy-sb-bgn flour blend was conducted and one paper was identified. the bacs reported in the study was noted and literature search of the various biological activities of such compounds and their mechanisms of actions were conducted. the results were documented and discussed. Results and Discussion: the study revealed that thiadiazole, stilbene, aziridine, thiourea, amphetamine/phenylethylene, artemisinin, monoterpenoids, naphthalenes, i,4-diazpanes, phenols and flavanoids were the identified bacs in cy-sb-bgn flour blend formulations with both the pure and ternary blends showing different family classifications of compounds and different types of compounds in one family class. the biological activities and mechanisms of actions included antimicrobial, antioxidant, antiinflammatory and antidiabetic activities with reported mechanisms of actions for each of these invivo activities. Conclusion: there are bacs in cy-sb-bgn formulations which are reported from studies to possess anti-microbial, anti-inflammatory, anti-oxidant and anti-diabetic properties invivo, with very established mechanisms of actions, making the use of such plant foods in disease management scientific, hence the recommendation of such plant foods use as adjunct in chronic disease management. Keywords: Bioactive compounds, Plant foods, Cocoyam, Soya Bean, Bambara Groundnut

Eco‐Evolutionary Consequences of Selective Exploitation on Metapopulations Illustrated With Atlantic Salmon

ABSTRACTAlthough the eco‐evolutionary consequences of dispersal and exploitation are increasingly recognised, consideration of these effects and how they interact for management and conservation remains limited. We addressed this gap by examining population exploitation within a metapopulation framework, using Atlantic salmon as a case study. We compared eco‐evolutionary consequences of alternative exploitation strategies by incorporating selective exploitation based on life‐history traits and spatial dimension of exploitation (i.e., whether populations were net exporters or importers of individuals). We used a demo‐genetic agent‐based model to examine demographic and evolutionary consequences of these strategies across a gradient of population‐specific exploitation rates. At the metapopulation scale, we found both lower abundance and earlier sexual maturation with increasing exploitation, particularly when fishing was selective on larger individuals. The spatial selectivity of exploitation had an overall additional detrimental effect on metapopulation performance and fisheries yield, and induced stronger evolutionary changes than when exploitation was evenly spread over all populations. We discuss the implications of metapopulation functioning for species management and how considering dispersal patterns and intensity might change how we apply harvest. Nevertheless, our findings suggest that the safest approach remains to distribute exploitation efforts evenly across all populations, especially in the absence of variation in intrinsic productivity. However, this strategy might not completely prevent negative consequences at the local scale. Therefore, we advise managers to critically assess the relevance of our results and dispersal assumptions in the specific cases they may have to deal with.

Green Chemistry Within the Circular Bioeconomy to Harness Chestnut Burr Extract’s Synergistic Antimicrobial Activity Against Helicobacter pylori

Green chemistry principles are pivotal in driving sustainable and innovative solutions to global health challenges. This study explores a hydroalcoholic extract from Castanea sativa (chestnut) burrs, an underutilized natural resource, as a potent source of antimicrobial compounds against Helicobacter pylori (H. pylori). The extract demonstrated significant bactericidal activity, synergizing effectively with clarithromycin and showing additive effects with metronidazole. Remarkably, combining the extract with clarithromycin and sub-inhibitory concentrations of pantoprazole reduced clarithromycin’s Minimum Bactericidal Concentration (MBC) to just 1.56% of its original value. Mechanistic studies suggest that the extract’s polyphenolic compounds compromise bacterial membrane integrity, enhancing antibiotic uptake, while pantoprazole disrupts bacterial ATPase activity. This research highlights the critical role of natural product extraction within the framework of green chemistry, offering a sustainable and environmentally friendly alternative to synthetic antimicrobials. By harnessing bioactive compounds from plant sources, this approach addresses the pressing issue of antibiotic resistance while promoting the responsible use of natural resources. The findings underscore the transformative potential of green chemistry in developing effective, eco-conscious antimicrobial therapies that align with global sustainability goals.

Deep eutectic solvent enhances antibacterial activity of a modular lytic enzyme against Acinetobacter baumannii

In this study, we evaluated the combined effect between MLE-15, a modular lytic enzyme composed of four building blocks, and reline, a natural deep eutectic solvent. The bioinformatic analysis allowed us to determine the spatial architecture of MLE-15, whose components were bactericidal peptide cecropin A connected via a flexible linker to the cell wall binding domain (CBD) of mesophilic 201ϕ2 − 1 endolysin and catalytic domain (EAD) of highly thermostable Ph2119 endolysin. The modular enzyme showed high thermostability with the melting temperature of 93.97 ± 0.38 °C, significantly higher than their natural counterparts derived from mesophilic sources. The minimum inhibitory concentration (MIC) of MLE-15 was 100 µg/mL for a panel of Gram-positive and Gram-negative bacteria, while the MIC of reline ranged from 6.25 to 25% v/v for the same strains. The addition of reline effectively reduced the MIC of MLE-15 from 100 µg/mL to 3.15–50 µg/mL. This combination displayed additive effects for most strains and synergism for extensively antibiotic-resistant Acinetobacter baumannii and Bacillus subtilis. The subsequent evaluation revealed that MLE-15 eliminated planktonic cells of A. baumannii RUH134, but was ineffective against matured biofilms. However, combined with reline, MLE-15 reduced the bacterial load in the matured biofilm by 1.39 log units. Confocal fluorescence microscopy indicated that reline damaged the structure of the biofilm, allowing MLE-15 to penetrate it. Additionally, MLE-15 and its combination with reline eradicated meropenem-persistent cells of A. baumannii RUH134. Effectiveness in lowering the MIC value of MLE-15 as well as protection against antibiotic-tolerant persister cells, indicate that MLE-15 and reline combination is a promising candidate for effective therapies in bacterial infections, which is especially important in the light of the global crisis of antimicrobial resistance.

Additive Effects of Natural Plant Extracts/Essential Oils and Probiotics as an Antipathogenic Topical Skin Patch Solution for Acne and Eczema

Additive Effects of Natural Plant Extracts/Essential Oils and Probiotics as an Antipathogenic Topical Skin Patch Solution for Acne and Eczema

Genotype by year interaction and additive and epistasis gene effects for Fusarium stalk rot resistance in doubled haploid lines of maize (Zea mays L.).

Fusarium stalk rot is the main factor reducing the quality of maize grain and leads to significant yield losses, which that ranges from 20 to 100%, depending on the degree of infection and weather conditions. Understanding its genetic mechanism is key to improving grain quality and ultimate yield. An experiment with 26 doubled haploid (DH) lines of maize was conducted in the northern part of the Lower Silesia Province in Poland over a ten-year period (2013-2022). The study assessed resistance to Fusarium stalk rot. The objectives were to evaluate genotype-year interactions for resistance to Fusarium stalk rot in maize DH lines using the additive main effects and multiplicative interaction (AMMI) model, to select DH lines that are stable across all years of testing and specific to particular environmental conditions, and to estimate additive and epistatic effects. AMMI results demonstrated a significant effect of genotype, year, and their interaction on Fusarium stalk rot resistance. The KN16 line is recommended for inclusion in further research within the breeding program due to its excellent stability and high average resistance to Fusarium stalk rot. Estimates of additive gene action effects were statistically significant in each year of the study. Estimates of epistasis (total additive by additive interaction) effects for Fusarium stalk rot resistance were also statistically significant in all ten years of the study. Only in 2013 was the epistasis effect positive (0.168). These results indicate that achieving biological advances in resistance to Fusarium stalk rot should be an important focus of ongoing maize breeding programs.

Terminal complement complex deposition on chondrocytes promotes premature senescence in age- and trauma-related osteoarthritis

BackgroundThe complement system is locally activated after joint injuries and leads to the deposition of the terminal complement complex (TCC). Sublytic TCC deposition is associated with phenotypical alterations of human articular chondrocytes (hAC) and enhanced release of inflammatory cytokines. Chronic inflammation is a known driver of chondrosenescence in osteoarthritis (OA). Therefore, we investigated whether TCC deposition contributes to stress-induced premature senescence (SIPS) during aging in vivo and after ex vivo cartilage injury.MethodsFemoral condyles of male 13-week-old and 72-week-old CD59-ko (higher TCC deposition), C6-deficient (insufficient TCC formation), and C57BL/6 (WT) mice were collected to assess age-related OA. Furthermore, macroscopically intact human and porcine cartilage explants were traumatized and cultured with/without 30% human serum (HS) to activate the complement system. Explants were additionally treated with clusterin (CLU, TCC inhibitor), N-acetylcysteine (NAC, antioxidant), Sarilumab (IL-6 receptor inhibitor), STAT3-IN-1 (STAT3 inhibitor), or IL-1 receptor antagonist (IL-1RA) in order to investigate the consequences of TCC deposition. Gene and protein expression of senescence-associated markers such as CDKN1A and CDKN2A was determined.ResultsIn the murine aging model, CD59-ko mice developed after 72 weeks more severe OA compared to C6-deficient and WT mice. mRNA analysis revealed that the expression of Cdkn1a, Cdkn2a, Tp53, Il1b, and Il6 was significantly increased in the cartilage of CD59-ko mice. In human cartilage, trauma and subsequent stimulation with HS increased mRNA levels of CDKN1A, CDKN2A, and IL6, while inhibition of TCC formation by CLU reduced the expression. Antioxidative therapy with NAC had no anti-senescent effect. In porcine tissue, HS exposure and trauma had additive effects on the number of CDKN2A-positive cells, while Sarilumab, STAT-IN-1, and IL-1RA reduced CDKN2A expression by trend.ConclusionOur results demonstrate that complement activation and consequent TCC deposition is associated with chondrosenescence in age-related and trauma-induced OA. We provided evidence that the SIPS-like phenotype is more likely induced by TCC-mediated cytokine release rather than oxidative stress. Overall, targeting TCC formation could be a future approach to attenuate OA progression.

LiOH Additive Triggering Beneficial Aging Effect of SnO2 Nanocrystal Colloids for Efficient Wide-Bandgap Perovskite Solar Cells.

Commercial SnO2 nanocrystals used for producing electron transporting layers (ETLs) of perovskite solar cells (PSC) are prone to aggregation at room temperature and contain many structural defects. Herein, we report that the LiOH additive can simultaneously delay the aggregation and donate the beneficial aging effect to SnO2 nanocrystals. The resulting SnO2 ETLs show the desired characteristics, including a broadened absorption range, reduced defects, improved transporting properties, and decreased work function. Meanwhile, perovskite Cs0.15FA0.65MA0.20Pb(I0.80Br0.20)3 films with a wide bandgap of 1.68 eV grown on them exhibit the pure phase, higher crystallinity, fewer defects, better buried-interface contact, and more aligned energy levels with each other than the ones based on SnO2 nanocrystals without the LiOH additive and aging treatment. Hence, the average efficiencies are boosted from (18.79 ± 0.40)% to (20.16 ± 0.36)% for the resulting wide-bandgap PSCs, wherein the champion efficiency of 21.12% is achieved. In addition, the as-obtained PSCs possess good thermal and humidity stability.

Bilayer TiO2/Mo-BiVO4 Photoelectrocatalysts for Ibuprofen Degradation

Heterojunction formation between BiVO4 nanomaterials and benchmark semiconductor photocatalysts has been keenly pursued as a promising approach to improve charge transport and charge separation via interfacial electron transfer for the photoelectrocatalytic degradation of recalcitrant pharmaceutical pollutants. In this work, a heterostructured TiO2/Mo-BiVO4 bilayer photoanode was fabricated by the deposition of a mesoporous TiO2 overlayer using the benchmark P25 titania catalyst on top of Mo-doped BiVO4 inverse opal films as the supporting layer, which intrinsically absorbs visible light below 490 nm, while offering improved charge transport. A porous P25/Mo-BiVO4 bilayer structure was produced from the densification of the inverse opal underlayer after post-thermal annealing, which was evaluated on photocurrent generation in aqueous electrolyte and the photoelectrocatalytic degradation of the refractory anti-inflammatory drug ibuprofen under back-side illumination by visible and UV–Vis light. Significantly enhanced photoelectrochemical performance on both photocurrent density and pharmaceutical degradation was achieved for the bilayer structure with respect to the additive effect of the constituent layers, which was related to the improved light harvesting arising from the backscattering by the mesoporous TiO2 layer in combination with the favorable charge transfer at the TiO2/Mo-BiVO4 interface.

Therapeutic Neuroscience Education In Fibromyalgia: A Randomized Controlled Trial

Abstract To investigate additive effect of Therapeutic Neuroscience Education (TNE) to pilates exercises in female patients with fibromyalgia (FM).25 female patients FM included in the study. They randomly separated into two groups. There were 11 patients in the intervention group and 14 patients in the control group. Pilates exercises and TNE were applied in the intervention group, and only pilates exercises were applied in the control group. Dynamic Loewenstein Occupational Therapy Cognitive Assessment (DLOTCA), Visual Analogue Scale (VAS), Brief Pain Inventory (BPI), Widespread Pain Index (WPI), Fibromyalgia Impact Questionnare (FIQ), Symptom Severity Scale (SSS), Pain Catastrophizing Scale (PCS), Tampa Scale for Kinesiophobia (TSK), Biopsychosocial Questionnaire (BETY-BQ) and pressure algometer was used for evaluation.After the treatment, control group improved in the “visuomotor construction” and “thinking operations"cognitive areas andtotal score of DLOTCA, BPI-pain severity score, VAS, FIQ, SSS, PCS-magnification, and only left medial knee mean score of pressure pain thresholds (p<0.05). Intervention group improved in the “thinking operations” cognitive area and total score of DLOTCA, BPI-pain severity score, BPI-pain interference score, VAS, WPI, FIQ, SSS, TSK, BETY-BQ and all pressure pain thresholds (excluding left trapezius) (p<0.05). In the comparison of delta values, the intervention group improved more in WPI, FIQ, right trapezius mean score and left trapezius, right quadriceps femoris, right-left medial knee maximum and mean scores of pressure pain thresholds (p<0.05). TNE increased the effectiveness of pilates exercises on pain, functional status and pressure pain thresholds in patients with FM.

Enhancing the Trapping of Melon Fruit Fly, Zeugodacus cucurbitae Coquilette through Synergizing the Odour and Visual Cues

The melon fruit fly (Zeugodacus cucurbitae Coquillett) poses a significant threat to cucurbit crops with substantial yield losses and challenging sustainable vegetable production. This study systematically investigated efficient color-based visual cues for attracting melon flies and explored the synergistic effects of these visual cues in conjunction with odour cues. This study was conducted in Agricultural College and Research Institute, TNAU, Madurai during 2024. Our studies included investigations on preferred colour by melon fly through olfactometer & insect cage bioassays in no choice & multiple choice conditions. The additive effect of the preferred colour when combined with the fruit fly attractive odour cue was investigated under field conditions. For both male and female melon fruit flies, yellow colour (RBG coordinates - 255:255:0) consistently emerged as the most efficient visual cue followed by white (255:255:255) and red (255:0:0). Field trials also confirmed the attractiveness of yellow colour as it outperformed other colours. The visual cue, yellow colour and odour cue (synthetic blend of four fruit fly EAG active synthetic compounds in a known ratio) were combined and found to be synergistic as this fusing captured significantly more flies than the either cues alone. These results highlighted the yellow colour as the most attractive visual cue for melon flies and combining effective of visual cues with established odour attractant to greatly enhance the trapping efficiency. This integrated approach offers a promising strategy for the management of melon fly and reduction of reliance on chemical pesticides contributing to more sustainable pest control in cucurbit production. The findings have significant implications for pest management strategies, especially in regions facing melon fly infestations that threaten crop yields and export potential.

The androgen clock is an epigenetic predictor of long-term male hormone exposure

Aging is a complex process characterized by biological decline and a wide range of molecular alterations to cells, including changes to DNA methylation. In this study, we used a male-specific epigenetic marker of aging to build an epigenetic predictor that measures long-term androgen exposure in sheep and mice (median absolute error of 4.3 and 1.4 mo, respectively). We term this predictor the androgen clock and show its "tick" is mediated by the androgen receptor and can be accelerated beyond that in normal male mice by supplementing females with dihydrotestosterone. Conversely, the removal of androgens by castration in sheep completely halted the androgen clock. In addition to potential applications in medicine and agriculture, we predict the androgen clock will prove a useful model to understand the mechanisms and processes of age-associated DNA methylation change because it can be precisely enhanced and halted using small molecule manipulation with few additional effects on the cell.

Myeloid Cells Induce Infiltration and Activation of B Cells and CD4+ T Follicular Helper Cells to Sensitize Brain Metastases to Combination Immunotherapy.

Brain metastasis (BM) is a poor prognostic factor in cancer patients. Despite showing efficacy in many extracranial tumors, immunotherapy with anti-PD-1 monoclonal antibody (mAb) or anti-CTLA-4 mAb appears to be less effective against intracranial tumors. Promisingly, recent clinical studies have reported that combination therapy with anti-PD-1 and anti-CTLA-4 mAbs has a potent antitumor effect on BM, highlighting the need to elucidate the detailed mechanisms controlling the intracranial tumor microenvironment (TME) to develop effective immunotherapeutic strategies. Here, we analyzed the tumor-infiltrating lymphocytes in murine models of BM that responded to anti-CTLA-4 mAb to anti-PD-1 mAb. Activated CD4+ T follicular helper (TFH) cells with high CTLA-4 expression characteristically infiltrated the intracranial TME, which were activated by the combination anti-CTLA-4 and anti-PD-1 treatment. Loss of TFH cells suppressed the additive effect of CTLA-4 blockade on anti-PD-1 mAb. B cell-activating factor belonging to the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) produced by abundant myeloid cells, particularly CD80hiCD206lo pro-inflammatory M1-like macrophages, in the intracranial TME, induced B cell and TFH cell infiltration and activation. Furthermore, the intracranial TME of patients with non-small cell lung cancer featured TFH and B cell infiltration as tertiary lymphoid structures. Together, these findings provide insights into the immune cell crosstalk in the intracranial TME that facilitates an additive anti-tumor effect of CTLA-4 blockade with anti-PD-1 treatment, supporting the potential of a combination immunotherapeutic strategy for BM.

Genetic inbreeding load and its individual prediction for milk yield in French dairy sheep

BackgroundThe magnitude of inbreeding depression depends on the recessive burden of the individual, which can be traced back to the hidden (recessive) inbreeding load among ancestors. However, these ancestors carry different alleles at potentially deleterious loci and therefore there is individual variability of this inbreeding load. Estimation of the additive genetic value for inbreeding load is possible using a decomposition of inbreeding in partial inbreeding components due to ancestors. Both the magnitude of variation in partial inbreeding components and the additive genetic variance of inbreeding loads are largely unknown. Our study had three objectives. First, based on substitution effect under non-random matings, we showed analytically that inbreeding load of an ancestor can be expressed as an additive genetic effect. Second, we analysed the structure of individual inbreeding by examining the contributions of specific ancestors/founders using the concept of partial inbreeding coefficients in three French dairy sheep populations (Basco-Béarnaise, Manech Tête Noire and Manech Tête Rousse). Third, we included these coefficients in a mixed model as random regression covariates, to predict genetic variance and breeding values of the inbreeding load for milk yield in the same breeds.ResultsPedigrees included 190,276, 166,028 and 633,655 animals of Basco-Béarnaise, Manech Tête Noire and Manech Tête Rousse, respectively, born between 1985 and 2021. A fraction of 99.1% of the partial inbreeding coefficients were lower than 0.01 in all breeds, meaning that in practice inbreeding occurs in pedigree loops that span several generations backwards. Less than 5% ancestors generate inbreeding, because mating is essentially between unrelated individuals. Inbreeding load estimations involved 658,731, 541,180 and 2,168,454 records of yearly milk yield from 178,123, 151,863 and 596,586 females in Basco-Béarnaise, Manech Tête Noire and Manech Tête Rousse, respectively. Adding the inbreeding load effect to the model improved the fitting (values of the statistic Likelihood Ratio Test between 132 and 383) for milk yield in the three breeds. The inbreeding load variances were equal to 11,804 and 9435 L squared of milk yield for a fully inbred (100%) descendant in Manech Tête Noire and Manech Tête Rousse. In Basco-Béarnaise, the estimate of the inbreeding load variance (11,804) was not significantly different from zero. The correlations between (direct effect) additive genetic and inbreeding load effects were − 0.09, − 0.08 and − 0.12 in Basco-Béarnaise, Manech Tête Noire and Manech Tête Rousse.ConclusionsThe decomposition of inbreeding in partial coefficients in these populations shows that inbreeding is mostly due to several small contributions of ancestors (lower than 0.001) going back several generations (5 to 7 generations), which is according to the policy of avoiding close matings. There is variation of inbreeding load among animals, although its magnitude does not seem enough to warrant selection based on this criterion.

Anti-inflammatory and analgesic effects of Filipendula ulmaria extract

The present study investigated the chemical content, analgesic, and anti-inflammatory properties of Filipendula ulmaria (L.) Maxim. (meadowsweet) aerial part extract. F. ulmaria is native to Bulgaria. Based on its phytochemicals, meadowsweet has a vast range of pharmacological activities, like antipyretic, analgesic, anti-inflammatory, antirheumatic, immunostimulating, anti-microbial, anti-allergic, and gastroprotective activity. In our experiment, F. ulmaria aerial part extract was practically non-toxic (oral LD50 > 2000 mg/kg). The performed experiments revealed that diclofenac possesses better anti-inflammatory and antinociceptive activity than F. ulmaria extracts (100 and 200 mg/kg). The results revealed a dose-dependent moderate inhibition of the inflammation and pain induced by 3 days of oral pretreatment with methanolic extract of F. ulmaria extracts. No additive effect of FUA extracts on the effects of diclofenac was noted. F. ulmaria extracts did not induce any alterations in blood biochemical analysis.

Muscle Contraction Is Essential for Tendon Healing and Muscle Function Recovery After Achilles Tendon Rupture and Surgical Repair.

Incomplete tendon healing and postponed muscle weakness after Achilles tendon rupture and surgical repair lead to poor performance in patient activities. Although the effectiveness of postoperative early functional rehabilitation has been proven, the priority and each effect of specific methods in early rehabilitation remain unclear. We hypothesized early muscle contraction exercises without joint motion would promote tendon healing and prevent calf muscle atrophy; in contrast, early static stretching after surgical repair would not contribute to tendon healing and induce calf muscle atrophy. C57Bl/6 mice underwent Achilles tendon rupture and suture repair, followed by different methods of post-surgery interventions: a non-exercise group, a Static stretching group, and an Electrical muscle stimulation group. 3 and 5 weeks after surgery, we assessed ex vivo tendon mechanical properties, collagen fiber alignment, and histological muscle properties. Electrical Muscle Stimulation restored the recovery of tendon mechanical properties and muscle strength more quickly than Static stretching. Static stretching had no additional effect on them compared to the non-exercise. Our results suggested that calf muscle contraction was essential as a post-surgery early functional rehabilitation to load tensile forces on tendons and improve Achilles tendon healing. Additionally, early muscle contractions naturally promote restoring muscle function after the rupture, but further research is needed to optimize muscle contraction protocols.

Refining PREVENT prediction models for 10-year risk of cardiovascular disease using measures of anxiety and depression

Refining PREVENT prediction models for 10-year risk of cardiovascular disease using measures of anxiety and depression

Effects of different approaches of infraclavicular brachial plexus block on perfusion index and tissue perfusion.

Although both the lateral sagittal and costoclavicular approaches are applied at the cord level in the infraclavicular region, there is a major difference between the distributions of the two approaches. We aimed to investigate the effects of this different distribution on tissue perfusion and oxygenation. Sixty patients undergoing elective elbow, forearm, wrist and hand surgery under infraclavicular brachial plexus block were included in the study. Patients were divided into two groups: group CC (costoclavicular approach, n = 30) and group LS (lateral sagittal approach, n = 30). The primary outcomes of this study were increased perfusion index (PI) and tissue oxygen saturation (StO2) rate. Secondary outcomes were the duration of block application, sensory and motor block onset time, time to first analgesic need and duration of motor block. The PI and StO2 increased significantly from baseline to each time point in both groups; however, there were no significant differences between the groups. The time to reach the sensory block stage was shorter with the costoclavicular approach. The duration of block application was shorter when using the costoclavicular approach. There were no differences between the approaches in terms of the time to the first analgesic requirement or need for additional analgesics. The different distributions of the two different approaches to infraclavicular brachial plexus block, costoclavicular and lateral sagittal, did not have an additional effect on tissue perfusion and oxygenation. Both approaches can be preferred especially in surgeries in which an increase in tissue perfusion is desired owing to perfusion-enhancing properties. NCT04764591.

Inhibitory effects of the combination of rapamycin with gemcitabine plus paclitaxel on the growth of pancreatic cancer tumors

We previously examined the antitumor effects of short interfering RNA nanoparticles targeting mammalian target of rapamycin (mTOR) in an orthotopic pancreatic cancer mouse model. We herein report the inhibitory effects of the mTOR inhibitor rapamycin on tumor growth in a novel established mouse model of pancreatic cancer using human pancreatic cancer cell line-derived organoids. Gemcitabine, 5-fluorouracil, and gemcitabine plus nab-paclitaxel are clinically used to treat advanced pancreatic cancer. In vitro assays showed that rapamycin strongly inhibited cell invasion, while gemcitabine, 5-fluorouracil, and gemcitabine plus paclitaxel primarily inhibited cell proliferation with minimal effects on invasion. In vivo mouse experiments demonstrated that rapamycin exhibited superior antitumor activity to S-1 (a metabolically activated prodrug of 5-fluorouracil) and another mTOR inhibitor, everolimus, while its efficacy was similar to that of gemcitabine plus paclitaxel (which was used instead of nab-paclitaxel due to concerns about allergic reactions in mice to human albumin) in a mouse model of pancreatic cancer using human pancreatic cancer cell line-derived organoids. Furthermore, the combination of rapamycin with gemcitabine plus paclitaxel exerted synergistic inhibitory effects on the growth of pancreatic cancer tumors. Although the inhibition of tumor growth was significantly stronger in everolimus-treated mice than in control mice, there were no additive anti-growth effects when combined with gemcitabine plus paclitaxel. The present results suggest that the combination of rapamycin with gemcitabine plus paclitaxel achieved the greatest reduction in tumor volumes in the mouse xenograft model and, thus, has significant clinical promise.

Synergistic Anti-tumorigenic Effects of Cabazitaxel and Usnic Acid Combination on Metastatic Castration-Resistant Prostate Cancer Cells.

Prostate cancer (PC) affects millions of men, causing high mortality rates. Despite the treatment approaches, the options for metastatic castration-resistant prostate cancer (mCRPC), a lethal form of advanced PC, are still limited. Cabazitaxel (Cbx) is the last taxane-derived chemotherapeutic approved for Docetaxel- resistant mCRPC patients. However, its effects are limited due to the activation of several pathways. Therefore, new approaches are needed to increase the efficacy of Cbx. Usnic acid (UA) is a natural product with wellknown anti-tumorigenic and synergistic effects with various chemotherapeutics. Although the cytotoxicity of UA and Cbx has been evaluated on mCRPC cells, the anti-tumorigenic effect of UA combination with any taxane has not been investigated yet. Thus, we aimed to evaluate the possible synergistic effect of Cbx+UA in mCRPC cells. Cell viability and apoptosis were analyzed using WST-1 and Annexin-V. Morphological changes were visualized by fluorescent staining. Finally, cell cycle, mitochondrial health, and ROS levels were determined. Based on WST-1 results, 25 μM UA exhibited significant additive and synergistic effects with the use of Cbx. Annexin V and cell cycle results showed that UA significantly enhanced the Cbx efficacy at increasing doses compared to using only Cbx (**p<0.01). Moreover, combined treatment significantly increased ROS levels and mitochondrial membrane depolarization compared with Cbx alone (**p<0.01). Thus, the results suggest that UA increased the anti-tumorigenic effects of Cbx on mCRPC cells by increasing apoptosis, causing an increase in intracellular ROS and disrupting mitochondrial health. Consequently, combining UA and Cbx offers a new combined therapeutic strategy for mCRPC treatment.