SODIUM LACTATE

This study aimed to elucidate the mechanism of Lactate Dehydrogenase A (LDHA) in senescent fibroblast-derived exosomes during skin photoaging, focusing on the molecular pathway by which it regulates Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) expression through histone lactylation, thereby inducing ferroptosis and accelerating skin photoaging. An ultraviolet B (UVB)-induced senescence model was established using human foreskin fibroblasts. Exosomes were isolated from senescent fibroblasts and characterized. Their features and uptake were assessed using Western blot, transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and immunofluorescence. Small interfering RNA was employed to knock down LDHA and ACSL4 gene. Pharmacological inhibitors (FX11, Ferrostatin-1) and sodium lactate rescue experiments were utilized. Lactate levels, histone H3K18 lactylation modification, ACSL4 transcriptional activity, and ferroptosis markers were detected to assess the effects of ACSL4 gene lactylation on ferroptosis. The biological effects of exosomal LDHA in photoaged tissue were validated using an in vivo UVB-irradiated mouse model. UVB irradiation induced fibroblast senescence and significantly upregulated LDHA expression. Exosomes from senescent fibroblasts were effectively taken up by HaCaT cells, leading to increased lactate levels and enhanced histone H3K18 lactylation in recipient cells. LDHA knockdown or inhibition downregulated ACSL4 expression and suppressed ferroptosis, whereas exogenous lactate partially restored these effects. RNA sequencing and ChIP-qPCR results indicated that LDHA-mediated lactylation modification was enriched at the ACSL4 promoter region, enhancing its transcriptional activity. In vivo experiments further confirmed that senescent exosomes accelerated UVB-induced skin collagen degradation and ferroptosis, while LDHA intervention significantly alleviated photoaging damage. Senescent fibroblast-derived exosomes deliver LDHA, promoting histone lactylation modification, which upregulates ACSL4 expression and activates the ferroptosis pathway, ultimately accelerating skin photoaging. This study reveals the coupling mechanism between metabolic signaling and epigenetic regulation in skin aging, providing new molecular targets and a theoretical basis for anti-photoaging therapy.

The human fingertip skin, with its interlocked epidermal-dermal architecture and dense tactile receptors, enables unique perception and inspires the design of innovative electronic skin (e-skin). However, most e-skin materials fail to replicate the hierarchical integration of composition, structure, and function found in natural skin. Drawing direct inspiration from the dermal extracellular matrix-a composite hydrogel reinforced by a collagen-hyaluronic acid, here we report an e-skin that mimics key composition and architectural features of human skin. By incorporating sodium lactate and montmorillonite nanosheets into a gelatin matrix, we engineer a biomimic gel with mechanical and hydration properties similar to those of natural skin through dynamic ionic crosslinking and hydrogen bond networks. The microstructure resembling the dermal papillae is designed using a sandpaper-templating strategy. The resulting iontronic sensor achieves high sensitivity (466.3 kPa -1 ), rapid response (47 ms), and a wide pressure detection range (20 Pa-2000 kPa). We further develop a stretchable, ultrathin, hand-shaped iontronic sensor array that integrates seamlessly with a dexterous robotic hand, achieving precise, nondestructive grasping and high-fidelity, multichannel pressure mapping.

Adequate brain relaxation is a key aspect of anaesthetic management in brain surgery. The aim of this study was to assess the clinical effectiveness of intravenous hypertonic sodium lactate (HSL) for intra-operative brain relaxation in supratentorial brain tumour surgery. Double-blind, phase II randomised pilot trial. Tertiary care centre for neurosurgery. Adult patients admitted for planned supratentorial brain tumour surgery. The primary outcome was the proportion of patients presenting satisfactory brain relaxation, assessed by the surgeon after opening the dura using a validated 4-point scale. Secondary outcomes were blood lactate level at T 0 +30 min, T 0 +60 min and T 0 +180 min, and the rate of adverse events. Patients received either HSL 2.5 ml kg -1 (interventional group) or 20% mannitol 5 ml kg -1 (conventional group) infusion started at skin incision (T 0 ). Twenty-four and 22 patients were analysed in the interventional and conventional groups, respectively [age: 60 ± 12 vs. 57 ± 12 years; females: 7 (29%) vs. 11 (50%); ASA physical status >II: 2 (8%) vs. 4 (18%)]. The primary outcome was observed in 23 {96% [95% confidence interval (CI), 77 to 100]} patients in the interventional group and in 20 [91% (95% CI, 69 to 98)] patients in the conventional group ( P  = 0.60). Median [IQR] lactate levels peaked at T 0 +30 min, 8.20 [6.98 to 8.73] mmol l -1 , in the interventional group and were higher than in the conventional group at each time point. Six and one patients experienced hypokalaemia in the interventional and conventional groups, respectively. No adverse events related to HSL infusion were observed. Pilot data suggests that HSL could provide efficient brain relaxation in patients undergoing supratentorial brain tumour resection via craniotomy, but further adequately powered studies are needed to confirm its comparative efficacy with mannitol. ClinicalTrials.gov NCT04488874.

Mucosal-associated invariant T (MAIT) cells are unconventional T cells, which upon activation can display potent cytotoxic and cytokine-producing capabilities. Together, these features make MAIT cells promising candidates for cancer immunotherapy. In this study, we show that MAIT cells can be efficiently amplified in vitro, and these amplified MAIT cells are armed with potent anticancer functions, including the ability to produce significant amounts of effector molecules such as IFNγ and granzyme B. Excitingly, we demonstrate that MAIT cells can be redirected to potently kill cancerous cells using a clinically relevant bispecific monoclonal antibody. Furthermore, in an attempt to metabolically condition MAIT cells to improve function, we demonstrate that MAIT cells possess the molecular machinery to transport and metabolize lactate, an abundant metabolite within the solid tumor microenvironment. Activating MAIT cells in the presence of exogenous sodium lactate remodels their cellular metabolism, with a significant increase in mitochondrial metabolism. Functionally, this supports elevated production of effector molecules (IFNγ, granzymes A and B), leading to boosted engager mediated MAIT cell cytotoxicity. These data collectively show that MAIT cells can be pharmacologically directed to target cancer cells and in vitro conditioning using sodium lactate can enhance their anticancer capabilities through reprogrammed cellular metabolism. Our findings represent a novel strategy for a potential new adoptive cancer immunotherapy.

Cutaneous wounds are susceptible to metabolic imbalances, via hypoxia and the "Warburg effect," which can lead to excessive lactate accumulation, potentially delaying healing. It is also accepted that lactylation of histones and other proteins is important in the epigenetic regulation of cells. Thus, a greater understanding of how lactate affects fibroblasts could lead to new therapeutic approaches. This study aimed to investigate how lactate impacts transforming growth factor β1 (TGF-β1)- and interleukin (IL)-1β-induced transcriptional programs in normal human dermal fibroblasts (NHDFs). Quantitative real-time PCR was used to evaluate transcriptional changes in key remodeling markers in NHDFs treated with 40 to 100 mM of sodium lactate, 0.1 μM of dexamethasone-21-phosphate, 10 mM of 2-deoxy- d -glucose, 2.5 μM of oligomycin, 10 μM of lactoyl-coenzyme A (lactyl-COA), or 10 mM of sodium acetate and then activated with 10 ng/mL of TGF-β1 or 0.1 ng/mL of IL-1β for 24 hours. Total messenger RNA was then isolated, and ΔΔCp relative expression was calculated versus appropriate controls, normalized to the housekeeping gene, GAPDH . Fluorescent membrane integrity and (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays were also conducted to assess toxicity and metabolic changes, respectively. We observed that lactate dose-dependently inhibited TGF-β1-induced collagen type 1α1 ( COL1a1 ) and elastin ( ELN-1 ), as well as IL-1β-induced matrix metalloproteinase 3 ( MMP3 ) and matrix metalloproteinase 12 ( MMP12 ). The anti-inflammatory glucocorticoid, dexamethasone-21-phosphate, also inhibited cytokine-induced ELN , MMP3 , and MMP12 . Parallel analysis with 2-deoxy- d -glucose, oligomycin, lactyl-COA, and sodium acetate inferred that chromatin modifications and metabolic reprogramming may contribute to the observed lactate response in our model. In addition, metabolic reprogramming was confirmed via detection of elevated NAD(P)H-dehydrogenase activity. These findings suggest that, because of a potential biphasic response, high lactate treatment of NHDFs exhibits immunosuppressive effects, indicating that metabolic regulation may help mitigate tissue damage. Additionally, pharmacological manipulation of histone modifications or metabolic rebalancing may serve as intriguing therapeutic interventions.

Sweat carries a wealth of physiological information and is ideal for noninvasive health monitoring. Surface-enhanced Raman scattering (SERS) enables highly sensitive, multiplexed detection of sweat biomarkers, but its integration into wearable systems remains impractical due to the bulky nature of Raman spectrometers and laser sources. To address this limitation, we developed a wearable platform that focuses on in situ sweat collection and time-sequenced storage, enabling delayed, off-body high-sensitivity SERS detection. The system integrates a Janus microporous membrane with a wettability gradient, fabricated via femtosecond laser ablation and oxygen plasma etching, to achieve directional and continuous sweat collection from the skin. This is combined with a microfluidic chip containing burst valves that enable passive, time-sequenced sampling and storage of sweat over the course of exercise. For detection, a capillary-based SERS substrate was fabricated using a silver mirror reaction, achieving detection limits down to 1 mM for sodium lactate and urea. Characteristic peaks were clearly identified from human sweat samples. This work presents a feasible path for combining wearable sweat sensing with high-performance spectroscopic analysis, offering promising applications in personalized health monitoring and dynamic physiological assessment.

Food packaging is a major contributor to environmental pollution and is a concern among customers who are pushing the food industry towards innovative, sustainable, and biodegradable plastic-alternative packaging materials. The integration of biomolecules derived from agricultural waste has the potential to enhance the mechanical properties of these novel packaging materials. Additionally, incorporating antimicrobial agents can improve food safety and extend shelf life, thereby increasing the market acceptance of these environmentally friendly packaging solutions. Research was conducted to (1) develop and evaluate mechanical properties of plastic-alternative films with chicken skin gelatin and antimicrobials (a mixture of sodium lactate and sodium diacetate (LD)); and (2) evaluate the efficacy of the antimicrobial films against Listeria monocytogenes and microbiological spoilage of fully cooked, beef bologna. Through the 12-week storage, the LD biopolymer film initially exhibited bacteriostatic effects, followed by bactericidal (decrease of ∼2 log CFU/g), and again bacteriostatic effect on the pathogen during weeks 0-4, 5-6, and 7-12, respectively. The biopolymer film with antimicrobial reduced the spoilage microorganism's growth by 0.6 log CFU/g over the 12-weeks of storage. Our research demonstrates that biopolymer films can be incorporated with antimicrobials and can be highly effective in controlling Listeria monocytogenes in ready-to-eat (RTE) meat products during storage.

Hyperosmolar solutions are prescribed in neurosurgery patients to provide satisfactory intraoperative brain relaxation and to lower cerebral injuries related to surgical retractors. Mannitol is traditionally considered as the first-choice solution for brain relaxation in neurosurgery patients. Hypertonic sodium lactate infusion was reported to provide a higher and longer osmotic effect compared to mannitol in severely brain-injured patients and to prevent impaired cerebral energetics related to brain injuries. To date, the clinical effectiveness of hypertonic sodium lactate infusion has never been studied in neurosurgery patients. The hypothesis of the study is that hyperosmolar sodium lactate infusion may provide satisfactory intraoperative brain relaxation in patients undergoing scheduled craniotomy for supratentorial brain tumor resection. We designed a phase II randomized, controlled, double-blind, single-center pilot trial, and aim to include 50 adult patients scheduled for craniotomy for supratentorial brain tumor resection under general anesthesia. Patients will be randomized to receive either mannitol (conventional group) or hypertonic sodium lactate (intervention group) infusion at the time of skin incision. Brain relaxation (primary outcome) will be assessed immediately after opening the dura by the neurosurgeon blinded to the treatment allocated using a validated 4-point scale. The primary outcome is the proportion of satisfactory brain relaxation, defined as brain relaxation score of 3 or 4. This study was approved by the Ethics Committee (Comité de Protection des Personnes Est III) and authorized by the French Health Authority (Agence Nationale de Sécurité des Médicaments, Saint-Denis, France). The University Hospital of Besancon is the trial sponsor and the holder of all data and publication rights. Results of the study will be submitted for publication in a peer-review international medical journal and for presentation in abstract (oral or poster) in international peer-reviewed congresses. The trial is registered with ClinicalTrials.gov (Identifier: NCT04488874, principal investigator: Prof Guillaume Besch, date of registration: July 28, 2020).

Wearable sweat sensors provide real-time monitoring of biomarkers, enabling individuals to gain real-time insight into their health status. Current sensors primarily rely on electrochemical mechanisms, limiting their capacity for the concurrent detection of multiple analytes. Surface-enhanced Raman scattering spectroscopy offers an alternative approach by providing molecular fingerprint information to facilitate the identification of intricate analytes. In this study, we combine a wearable Janus fabric for efficient sweat collection and a grapefruit optical fiber embedded with Ag nanoparticles as a sensitive SERS probe. The Janus fabric features a superhydrophobic side in contact with the skin and patterned superhydrophilic regions on the opposite surface, facilitating the unidirectional flow of sweat toward these hydrophilic zones. Grapefruit optical fibers feature sharp tips with the ability to penetrate transparent dressings. Its microchannels extract sweat through capillary force, and nanoliter-scale volumes of sweat are sufficient to completely fill them. The Raman signal of sweat components is greatly enhanced by the plasmonic hot spots and accumulates along the fiber length. We demonstrate sensitive detection of sodium lactate and urea in sweat with a detection limit much lower than the physiological concentration levels. Moreover, the platform shows its capability for multicomponent detection and extends to the analysis of real human sweat.

Chitosan and composite fibers containing chitin nanofibrils have been developed for use in cosmetology. The tensile strength of the chitosan multifilaments is 160.6 ± 19.0 MPa, and of the composite multifilaments containing chitin, nanofibrils are 198.0 ± 18.4 MPa. Chitin nanofibrils introduced into the chitosan solution contribute to the creation of a new spatial arrangement of chitosan chains and their denser packing. The studies carried out by optical, scanning electron, and atomic force microscopy has shown that the serum, consisting of a mixture of lactic acid and sodium lactate, contains extended oriented structures-"liquid filaments". It has been also shown that a mixture of serum and composite fibers based on chitosan and chitin nanofibrils has mucoadhesive, film-forming properties. The introduction of composite fibers containing chitin nanofibrils into the serum promotes the reinforcing effect of liquid filaments, the lifting effect of the film. The obtained composition can be used in cosmetology as a skin care product.

Several UK military expeditions have successfully used physiological sensors to monitor participant's physiological responses to challenging environmental conditions. This article describes the development and trial of a multimodal wearable biosensor that was used during the first all-female unassisted ski crossing of the Antarctic land mass. The project successfully transmitted remote real-time physiological data back to the UK. The ergonomic and technical lessons identified have informed recommendations for future wearable devices. The biosensor devices were designed to be continuously worn against the skin and capture: HR, ECG, body surface temperature, bioimpedance, perspiration pH, sodium, lactate and glucose. The data were transmitted from the devices to an android smartphone using near-field technology. A custom-built App running on an android smartphone managed the secure transmission of the data to a UK research centre, using a commercially available satellite transceiver. Real-time physiological data, captured by the multimodal device, was successfully transmitted back to a UK research control centre on 6 occasions. Postexpedition feedback from the participants has contributed to the ergonomic and technical refinement of the next generation of devices. The future success of wearable technologies lies in establishing clinical confidence in the quality of the measured data and the accurate interpretation of those data in the context of the individual, the environment and activity being undertaken. In the near future, wearable physiological monitoring could improve point-of-care diagnostic accuracy and inform critical medical and command decisions.

Silanol (organic silicon) has been used for decades in the treatment of skin photoaging as it stabilizes and maintains skin structures through hydrogen bonding electrostatic interaction with extracellular matrix (ECM) proteins or glycosaminoglycans. Organic silicon-based products are often presented as silanol derivatives which are currently associated to other structural molecules such as orthohydroxybenzoate, carboxymethyl theophylline alginate, ascorbate, acetyltyrosine, sodium lactate or mannuronate. Consequently, organic silicon formulations may differ substantially between the medical devices available on the market, which may result in additional effect on the skin. Therefore, there is a real need for a better characterization of the products in terms of their action on human skin and in vitro skin model. In this in vitro study, the effect of RRS® Silisorg was analyzed. RRS® Silisorg is a dermal implant (CE Class III medical device) containing monomethylsilanol mannuronate associated to an antioxidant resveratrol. Skin fibroblast viability and capacity to induce the production of key ECM genes were evaluated in the presence of different concentrations of RRS® Silisorg. The key ECM genes selected were collagen type I, elastin and hyaluronan synthase type 2 (HAS2), which is the cellular enzyme responsible for high-molecular weight hyaluronic acid (HA) production. Viability was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and expression was quantified by quantitative polymerase chain reaction. RRS® Silisorg increased fibroblast gene expression of HAS2 in the first 24 hours, 25 times in the presence of 1 mg/mL of solution, followed by a collagen type I gene expression (4.7 times) and elastin expression (2.5 times) increase after 48 hours. These results demonstrate that the silanol-based medical device RRS® Silisorg sustains HA, collagen and elastin production in human skin fibroblasts in vitro.