Efficacy and safety of add-on sarcosine in patients with major depressive disorder: A randomized controlled trial.

The main hurdles with current therapies for major depressive disorder (MDD) include lack of efficacy, therapeutic latency, and adverse drug reactions. Add-on therapy to conventional antidepressants may result in better therapeutic outcomes to overcome these obstacles. Sarcosine (N-methyl glycine), an endogenous amino acid that acts by modulating the NMDA receptor, is available as a dietary supplement. So, the present study was planned to evaluate the efficacy and safety of add-on sarcosine to SSRIs in MDD. In the present randomized, double-blind clinical trial (NCT04975100), 60 eligible participants with MDD were randomly assigned to either the test group (SSRI + sarcosine) or the control group (SSRI + placebo). Clinical and biochemical parameters like MADRS, CGI, serum BDNF, and serum glycine were assessed at baseline and eight weeks. The mean reduction in MADRS score was significant in both the control (-8.7, 95% CI: -11.0 to -6.4, p < 0.001) and the test group (-13.3, 95% CI: -14.9 to -11.7, p < 0.001), but the change in the test group was significantly greater (-4.6, 95% CI: -7.5 to -1.7, p = 0.003). The test group had a significantly higher response rate (p = 0.007) and remission rate (p = 0.038) compared to the control group. There was a significant increase in serum BDNF in both groups; however, the change in the test group was significantly higher than in the control group (p = 0.041). Similarly, the test group had a significantly higher increase in serum glycine than the control group (p < 0.001). Sarcosine may be considered an efficacious and safe add-on therapy to standard SSRIs in the management of MDD. ClinicalTrial.gov IdentifierNCT04975100.

Dynamic role of GlyT1 as glycine sink or source: Pharmacological implications for the gain control of NMDA receptors.

Glycine transporter 1 (GlyT1) mediates the termination of inhibitory glycinergic receptor signaling in the spinal cord and brainstem, and is also present diffusely in the forebrain. Here, it regulates the ambient glycine concentration and influences the 'glycine' site occupancy of N-methyl-d-aspartate receptors (NMDARs). GlyT1 is a reversible transporter with a substantial, but not excessive, sodium-motive force for uphill transport. This study investigates its role as a potential source of glycine supply, either by reverse uptake or heteroexchange. Indeed, glutamate alone does not induce NMDAR current in "naive" oocytes co-expressing GluN1/GluN2A and GlyT1, a previously characterized cellular model. However, after substantial intracellular glycine accumulation, GlyT1 reverses its transport mode, and begins to release glycine into the external compartment, allowing NMDAR activation by glutamate alone. These uptake-dependent glutamate currents were blocked by ALX-5407 and potentiated by sarcosine, a specific inhibitor and substrate of GlyT1, respectively, suggesting a higher occupancy of the co-agonist site when GlyT1 functions as a glycine source either by reversed-uptake or by heteroexchange. These two glycine release mechanisms can be distinguished by their voltage dependence, as the reversed-uptake cycle decreases at hyperpolarized potentials, whereas heteroexchange electroneutrality preserves glycine efflux and NMDAR activation at these potentials. These results establish GlyT1-mediated efflux as a positive regulator of NMDAR coagonist site occupancy, and demonstrate the efficacy of sarcosine heteroexchange in enhancing coagonist site occupancy. Because NMDAR facilitation by GlyT1-inhibitors and sarcosine relies on different transport mechanisms, their actions may be a source of variability in reversing NMDAR hypofunction in schizophrenia.

A molecularly imprinting photoelectrochemical sensor based on Bi2O2S-sensitized perovskite Cs2AgBiBr6 for sarcosine determination.

An original molecular imprinting photoelectrochemical (PEC) sensor for sarcosine detection based on stable lead-free inorganic halide double perovskite Cs2AgBiBr6 is proposed. Cs2AgBiBr6 as a lead-free halide perovskite material possesses several positive optoelectronic properties for PEC analysis, such as long-lived component to the charge-carrier lifetime, and strong absorption of visible light. At the same time, two-dimensional materials also offer excellent electronic and mechanical properties; thus, Bi2O2S was used and combined with Cs2AgBiBr6 to provide a stable and large photocurrent, which also benefits from the  stability of perovskite Cs2AgBiBr6. Based on this novel PEC assay, the detection range for sarcosine was between 0.005 and 5000 ng/mL with a low detection limit of 0.002 ng/mL. This work also improved the adhibition of metal halide perovskite in analytical chemistry field, providing a novel way for other small molecule detection.

Enzymatic cascade reactors on carbon nanotube transistor detecting trace prostate cancer biomarker.

Biosensors based on carbon nanotube field-effect transistors (CNT-FETs) have shown great potential in biomarker detection due to their high sensitivity because of appreciable semiconducting electrical properties. However, background signal interferences in complex mediums may results in low signal-to-noise ratio, which may impose challenges for precise biomarker detection in physiological fluids. In this work, we develop an enzymatic CNT-FET, with scalable production at wafer scale, for detection of trace sarcosine that is a biopsy-correlated biomarker of prostate cancer. Enzymatic cascade rectors are constructed on the CNT to improve the reaction efficiency, thereby, enhancing the signal transduction. As such, a limit of detection as low as 105 zM is achieved in buffer solution. Owing to the enhanced reaction efficiency, the testing of clinical serum samples yields significant signal difference to discriminate the prostate cancer (PCa) samples from the benign prostatic hyperplasia (BPH) samples (P = 1.07 × 10-5), demonstrating immense potential in practical applications.

Dual-mode fluorescence and colorimetric smartphone-based sensing platform with oxidation-induced self-assembled nanoflowers for sarcosine detection.

BACKGROUND: Early prostatic cancer (PCa) diagnosis significantly improves the chances of successful treatment and enhances patient survival rates. Traditional enzyme cascade-based early cancer detection methods offer efficiency and signal amplification but are limited by cost, complexity, and enzyme dependency, affecting stability and practicality. Meanwhile, sarcosine (Sar) is commonly considered a biomarker for PCa development. It is essential to develop a Sar detection method based on cascade reactions, which should be efficient, low skill requirement, and suitable for on-site testing. RESULTS: To address this, our study introduces the synthesis of organic-inorganic self-assembled nanoflowers to optimize existing detection methods. The Sar oxidase (SOX)-inorganic hybrid nanoflowers (Cu3(PO4)2:Ce@SOX) possess inherent fluorescent properties and excellent peroxidase activity, coupled with efficient enzyme loading. Based on this, we have developed a dual-mode multi-enzyme cascade nanoplatform combining fluorescence and colorimetric methods for the detection of Sar. The encapsulation yield of Cu3(PO4)2:Ce@SOX reaches 84.5 %, exhibiting a remarkable enhancement in catalytic activity by 1.26-1.29 fold compared to free SOX. The present study employing a dual-signal mechanism encompasses 'turn-off' fluorescence signals ranging from 0.5 µM to 60 µM, with a detection limit of 0.226 µM, and 'turn-on' colorimetric signals ranging from 0.18 µM to 60 µM, with a detection limit of 0.120 µM. SIGNIFICANCE: Furthermore, our study developed an intelligent smartphone sensor system utilizing cotton swabs for real-time analysis of Sar without additional instruments. The nano-platform exhibits exceptional repeatability and stability, rendering it well-suited for detecting Sar in authentic human urine samples. This innovation allows for immediate analysis, offering valuable insights for portable and efficient biosensors applicable to Sar and other analytes.

Choline degradation in Paracoccus denitrificans: identification of sources of formaldehyde.

Paracoccus denitrificans is a facultative methylotroph that can grow on methanol and methylamine as sole sources of carbon and energy. Both are oxidized to formaldehyde and then to formate, so growth on C1 substrates induces the expression of genes encoding enzymes required for the oxidation of formaldehyde and formate. This induction involves a histidine kinase response regulator pair (FlhSR) that is likely triggered by formaldehyde. Catabolism of some complex organic substrates (e.g., choline and L-proline betaine) also generates formaldehyde. Thus, flhS and flhR mutants that fail to induce expression of the formaldehyde catabolic enzymes cannot grow on methanol, methylamine, and choline. Choline is oxidized to glycine via glycine betaine, dimethylglycine, and sarcosine. By exploring flhSR growth phenotypes and the activities of a promoter and enzyme known to be upregulated by formaldehyde, we identify the oxidative demethylations of glycine betaine, dimethylglycine, and sarcosine as sources of formaldehyde. Growth on glycine betaine, dimethylglycine, and sarcosine is accompanied by the production of up to three, two, and one equivalents of formaldehyde, respectively. Genetic evidence implicates two orthologous monooxygenases in the oxidation of glycine betaine. Interestingly, one of these appears to be a bifunctional enzyme that also oxidizes L-proline betaine (stachydrine). We present preliminary evidence to suggest that growth on L-proline betaine induces expression of a formaldehyde dehydrogenase distinct from the enzyme induced during growth on other formaldehyde-generating substrates.IMPORTANCEThe bacterial degradation of one-carbon compounds (methanol and methylamine) and some complex multi-carbon compounds (e.g., choline) generates formaldehyde. Formaldehyde is toxic and must be removed, which can be done by oxidation to formate and then to carbon dioxide. These oxidations provide a source of energy; in some species, the CO2 thus generated can be assimilated into biomass. Using the Gram-negative bacterium Paracoccus denitrificans as the experimental model, we infer that oxidation of choline to glycine generates up to three equivalents of formaldehyde, and we identify the three steps in the catabolic pathway that are responsible. Our work sheds further light on metabolic pathways that are likely important in a variety of environmental contexts.

Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome.

Introduction: A group of SARS-CoV-2 infected individuals present lingering symptoms, defined as long COVID (LC), that may last months or years post the onset of acute disease. A portion of LC patients have symptoms similar to myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), which results in a substantial reduction in their quality of life. A better understanding of the pathophysiology of LC, in particular, ME/CFS is urgently needed. Methods: We identified and studied metabolites and soluble biomarkers in plasma from LC individuals mainly exhibiting ME/CFS compared to age-sex-matched recovered individuals (R) without LC, acute COVID-19 patients (A), and to SARS-CoV-2 unexposed healthy individuals (HC). Results: Through these analyses, we identified alterations in several metabolomic pathways in LC vs other groups. Plasma metabolomics analysis showed that LC differed from the R and HC groups. Of note, the R group also exhibited a different metabolomic profile than HC. Moreover, we observed a significant elevation in the plasma pro-inflammatory biomarkers (e.g. IL-1α, IL-6, TNF-α, Flt-1, and sCD14) but the reduction in ATP in LC patients. Our results demonstrate that LC patients exhibit persistent metabolomic abnormalities 12 months after the acute COVID-19 disease. Of note, such metabolomic alterations can be observed in the R group 12 months after the acute disease. Hence, the metabolomic recovery period for infected individuals with SARS-CoV-2 might be long-lasting. In particular, we found a significant reduction in sarcosine and serine concentrations in LC patients, which was inversely correlated with depression, anxiety, and cognitive dysfunction scores. Conclusion: Our study findings provide a comprehensive metabolomic knowledge base and other soluble biomarkers for a better understanding of the pathophysiology of LC and suggests sarcosine and serine supplementations might have potential therapeutic implications in LC patients. Finally, our study reveals that LC disproportionally affects females more than males, as evidenced by nearly 70% of our LC patients being female.

Sarcosine dehydrogenase as an immune infiltration-associated biomarker for the prognosis of hepatocellular carcinoma.

This study was aimed to investigate the prognostic value and clinical significance of sarcosine dehydrogenase (SARDH) in hepatocellular carcinoma (HCC) and to explore the underlying mechanisms. The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), HPA and CPTAC databases were adopted to analyze the expression of SARDH mRNA and protein between normal liver tissue and HCC, and examine their relationship with clinicopathological features. Kaplan-Meier analysis, Cox regression, as well as nomogram were adopted to explore the prognostic value of SARDH in HCC. Gene Ontology (GO), Kyoto Gene and Genome Encyclopedia (KEGG) together with Gene Set Enrichment Analysis (GSEA) were adopted to analyze the molecular mechanisms and biological functions of SARDH in HCC; while MethSurv, STRING, GeneMANIA, TIMER database data and single-sample gene set enrichment analysis (ssGSEA) algorithm were used for other bioinformatic analysis. Furthermore, immunohistochemistry was used to verify the expression of SARDH. Compared to normal liver tissue, SARDH expression was markedly lower in HCC. A lower SARDH expression was linked with Pathologic T stage (T3&T4), pathologic stage (Stage III&IV), and histologic grade (G3&4), which further indicates worse prognosis. Besides, results of bioinformatic analysis proved that SARDH expression was correlated with immune infiltration. In addition, SARDH hypermethylation was related to a poorer prognosis. SARDH expression was related to several key genes in the Ferroptosis pathway.

Development of a highly sensitive fluorescent probe using Delonix regia (Gulmohar) tree pod shell for precise sarcosine detection in human urine samples: advancing prostate cancer diagnosis.

We designed a highly sensitive fluorescent sensor for the early detection of sarcosine, a potential biomarker for prostate cancer. This sensor was based on surface-cobalt-doped fluorescent carbon quantum dots (Co-CD) using a FRET-based photoluminescent sensing platform. Blue luminescent carbon quantum dots (CQD) were synthesised through a hydrothermal approach, utilizing Delonix regia tree pod shells. Cobalt was employed to functionalize the CQD, enhancing the quantum-entrapped effects and minimizing surface flaws. To optimize Co-CD preparation, we employed a Box-Behnken design (BBD), and response surface methodology (RSM) based on single-factor experiments. The Co-CD was then used as a fluorescent probe for selective Cu2+ detection, with Cu2+ quenching Co-CD fluorescence through an energy transfer process, referred to as 'turn-off'. When sarcosine was introduced, the fluorescence intensity of Co-CD was restored, creating a 'turn-on' response. The sensor exhibited a Cu2+ detection limit (LOD) of 2.4 µM with a linear range of 0 µM to 10 µM. The sarcosine detection in phosphate buffer saline (PBS, pH 7.4) resulted in an LOD of 1.54 µM and a linear range of 0 to 10 µM. Importantly, the sensor demonstrated its suitability for clinical analysis by detecting sarcosine in human urine. In summary, our rapid and highly sensitive sensor offers a novel approach for the detection of sarcosine in real samples, facilitating early prostate cancer diagnosis.Communicated by Ramaswamy H. Sarma.

Aptasensor based on high surface area covalent organic framework for simple and ultrasensitive detection of sarcosine in the diagnosis of prostate cancer.

In this study, an electrochemical aptasensor was developed for the specific detection of sarcosine using a covalent organic framework (COF). The imine-based two-dimensional COF was synthesized through a solvothermal process using terephthaldehyde and melamine. This resulted in the formation of a structure that is highly porous and has a unique surface area of 908 m2/g. The produced biosensor demonstrated a significant linear relationship between charge transfer resistance (Rct) and various concentrations of sarcosine in blood serum samples. The aptasensor had two linear ranges, spanning from 0.5 fM to 700 fM and 10 pM to 0.12 nM, respectively, with a detection limit of 0.15 fM. The incorporation of high surface area COFs in the aptasensor design offers a promising combination of sensitivity, stability, and specificity. This combination creates a valuable device for diagnosing and monitoring of prostate cancer and potentially other diseases.

SarCTAB: an efficient and cost-effective DNA isolation protocol from geophytes.

Geophytes are herbaceous plants that grow anew from underground buds and are excellent models to study storage organ formation. However, molecular studies involving geophytes are constrained due to the presence of a wide spectrum of polysaccharides and polyphenols that contaminate the genomic DNA. At present, several protocols exist for the extraction of genomic DNA from different plant species; however, isolating high-quality DNA from geophytes is challenging. Such challenges are further complexed by longer incubation time and multiple precipitation steps involved in existing DNA isolation methods. To overcome such problems, we aimed to establish a DNA extraction method (SarCTAB) which is an economical, quick, and sustainable way of DNA isolation from geophytes. We improved the traditional CTAB method by optimizing key ingredients such as sarcosine, ß-mercaptoethanol, and high molar concentration of sodium chloride (NaCl), which resulted in high concentration and good-quality DNA with lesser polysaccharides, proteins, and polyphenols. This method was evaluated to extract DNA from storage organs of six different geophytes. The SarCTAB method provides an average yield of 1755 ng/µl of high-quality DNA from 100 mg of underground storage tissues with an average standard purity of 1.86 (260/280) and 1.42 (260/230). The isolated genomic DNA performed well with Inter-simple sequence repeat (ISSR) amplification, restriction digestion with EcoRI, and PCR amplification of plant barcode genes viz. matK and rbcL. Also, the cost involved in DNA isolation was low when compared to that with commercially available kits. Overall, SarCTAB method works effectively to isolate high-quality genomic DNA in a cost-effective manner from the underground storage tissues of geophytes, and can be applied for next-generation sequencing, DNA barcoding, and whole genome bisulfite sequencing.

Biodegradation of selected aminophosphonates by the bacterial isolate Ochrobactrum sp. BTU1.

Aminophosphonates, like glyphosate (GS) or metal chelators such as ethylenediaminetetra(methylenephosphonic acid) (EDTMP), are released on a large scale worldwide. Here, we have characterized a bacterial strain capable of degrading synthetic aminophosphonates. The strain was isolated from LC/MS standard solution. Genome sequencing indicated that the strain belongs to the genus Ochrobactrum. Whole-genome classification using pyANI software to compute a pairwise ANI and other metrics between Brucella assemblies and Ochrobactrum contigs revealed that the bacterial strain is designated as Ochrobactrum sp. BTU1. Degradation batch tests with Ochrobactrum sp. BTU1 and the selected aminophosphonates GS, EDTMP, aminomethylphosphonic acid (AMPA), iminodi(methylene-phosphonic) (IDMP) and ethylaminobis(methylenephosphonic) acid (EABMP) showed that the strain can use all phosphonates as sole phosphorus source during phosphorus starvation. The highest growth rate was achieved with AMPA, while EDTMP and GS were least supportive for growth. Proteome analysis revealed that GS degradation is promoted by C-P lyase via the sarcosine pathway, i.e., initial cleavage at the C-P bond. We also identified C-P lyase to be responsible for degradation of EDTMP, EABMP, IDMP and AMPA. However, the identification of the metabolite ethylenediaminetri(methylenephosphonic acid) via LC/MS analysis in the test medium during EDTMP degradation indicates a different initial cleavage step as compared to GS. For EDTMP, it is evident that the initial cleavage occurs at the C-N bond. The detection of different key enzymes at regulated levels, form the bacterial proteoms during EDTMP exposure, further supports this finding. This study illustrates that widely used and structurally more complex aminophosphonates can be degraded by Ochrobactrum sp. BTU1 via the well-known degradation pathways but with different initial cleavage strategy compared to GS.

Photothermal biosensing integrated with microfluidic paper-based analytical device for sensitive quantification of sarcosine.

This article presents the development of a photothermal biosensing integrated with microfluidic paper-based analytical device (PT-µPAD) as a quantitative biosensor method for monitoring sarcosine in human control urine, plasma, and serum samples. The device utilizes gold nanoparticles (AuNPs) as both a peroxidase-like nanozyme and a photothermal substrate to enable sarcosine detection. In our PT-µPAD, hydrogen peroxide (H2O2) is generated through the oxidation of sarcosine by a sarcosine oxidase (SOx) enzyme. Subsequently, the H2O2 flows through the paper microchannels to the detection zone, where it etches the pre-deposited AuNPs, inducing a temperature change upon exposure by a 532 nm laser. The temperature variation is then measured using a portable and inexpensive infrared thermometer. Under optimized conditions, we obtained a linear range between 10.0 and 40.0 nmol L-1 (R2 = 0.9954) and a detection limit (LOD) of 32.0 pmol L-1. These values fall within the clinical range for sarcosine monitoring in prostate cancer diagnostics in humans. Moreover, our approach exhibits high selectivity without interfering effects. Recovery studies in various human control samples demonstrated a range of 99.05-102.11 % with the highest RSD of 2.25 %. The PT-µPAD was further validated for sarcosine determination in human control urine and compared with a commercial ELISA assay, revealing no significant difference between these two methods at a 95 % confidence level. Overall, our proposed sarcosine biosensor is well-suited for prostate cancer monitoring, given its affordability, sensitivity, and user-friendliness, even for unskilled individuals. Moreover, this strategy has promising prospects for broader applications, potentially detecting various biomarkers as a point-of-care (POC) diagnostic tool.

Oligosarcosine Conjugation of Arginine-Rich Peptides Improves the Intracellular Delivery of Peptide/pDNA Complexes.

Cell-penetrating peptides (CPPs), for example, arginine (Arg) rich peptides, are used for the intracellular delivery of nucleic acids. In this study, oligosarcosine-conjugated Arg-rich peptides were designed as plasmid DNA (pDNA) carriers, and the physicochemical parameters and transfection efficiency of the peptide/pDNA complexes were evaluated. Oligosarcosine with different lengths were conjugated to a base sequence composed of arginine and α-aminoisobutyric acid (Aib) [(Aib-Arg-Arg)3]. Oligosarcosine conjugation inhibited the aggregation of the complexes after mixing with pDNA, shielded the positive charge of the complexes, and provided efficient pDNA transfection in cultured cells. The efficiency of the pDNA transfection was improved by varying the length of the oligosarcosine moiety (10-15 units were optimal). The cellular uptake efficiency and intracellular distribution of pDNA were the same regardless of oligosarcosine conjugation. These results implied that intracellular processes, including the decondensation of pDNA, contributed to the efficiency of the protein expression from pDNA. This study demonstrated the advantages of oligosarcosine conjugation to Arg-rich CPPs and provided valuable insight into the future design of CPPs.

ERVK13-1/miR-873-5p/GNMT Axis Promotes Metastatic Potential in Human Bladder Cancer though Sarcosine Production.

N-methyl-glycine (sarcosine) is known to promote metastatic potential in some cancers; however, its effects on bladder cancer are unclear. T24 cells derived from invasive cancer highly expressed GNMT, and S-adenosyl methionine (SAM) treatment increased sarcosine production, promoting proliferation, invasion, anti-apoptotic survival, sphere formation, and drug resistance. In contrast, RT4 cells derived from non-invasive cancers expressed low GNMT, and SAM treatment did not produce sarcosine and did not promote malignant phenotypes. In T24 cells, the expression of miR-873-5p, which suppresses GNMT expression, was suppressed, and the expression of ERVK13-1, which sponges miR-873-5p, was increased. The growth of subcutaneous tumors, lung metastasis, and intratumoral GNMT expression in SAM-treated nude mice was suppressed in T24 cells with ERVK13-1 knockdown but promoted in RT4 cells treated with miR-873-5p inhibitor. An increase in mouse urinary sarcosine levels was observed to correlate with tumor weight. Immunostaining of 86 human bladder cancer cases showed that GNMT expression was higher in cases with muscle invasion and metastasis. Additionally, urinary sarcosine concentrations increased in cases of muscle invasion. Notably, urinary sarcosine concentration may serve as a marker for muscle invasion in bladder cancer; however, further investigation is necessitated.

Sarcosine May Induce EGF Production or Inhibit the Decline in EGF Concentrations in Patients with Chronic Schizophrenia (Results of the PULSAR Study).

Sarcosine (N-methylglycine), a glutamatergic modulator, reduces the primary negative symptoms of schizophrenia. These beneficial changes might be mediated by trophic factors such as epidermal growth factor (EGF). We assessed associations between initial serum EGF levels or changes in serum EGF levels and symptom severity during the addition of sarcosine to stable antipsychotic treatment and thereby evaluated the associations between glutamatergic modulation, clinical changes and peripheral EGF concentrations. Fifty-eight subjects with a diagnosis of chronic schizophrenia with dominant negative symptoms, stably treated with antipsychotics, completed a prospective 6-month, randomized, double-blind, placebo-controlled study. Subjects received orally 2 g of sarcosine (n = 28) or placebo (n = 30) daily. Serum EGF levels and symptom severity (using the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS)) were assessed at baseline, 6-week and 6-month follow-up. Augmentation antipsychotic treatment with sarcosine had no effect on EGF serum levels at any time points. Only the sarcosine group showed a significant improvement in negative symptoms, general psychopathology subscales and the overall PANSS score. We found a reduction in serum EGF levels in the placebo group, but levels in the sarcosine remained stable during the study. Our data indicate that improvement in negative symptoms due to sarcosine augmentation is not directly mediated by EGF, but effective treatment may induce the production or block the decrease in EGF concentrations, which indicates the neuroprotective effect of treatment and confirms the relationship between neuroprotection and EGF levels.

Salbutamol Attenuates Diabetic Skeletal Muscle Atrophy by Reducing Oxidative Stress, Myostatin/GDF-8, and Pro-Inflammatory Cytokines in Rats.

Type 2 diabetes is a metabolic disorder that leads to accelerated skeletal muscle atrophy. In this study, we aimed to evaluate the effect of salbutamol (SLB) on skeletal muscle atrophy in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic rats. Male Sprague Dawley rats were divided into four groups (n = 6): control, SLB, HFD/STZ, and HFD/STZ + SLB (6 mg/kg orally for four weeks). After the last dose of SLB, rats were assessed for muscle grip strength and muscle coordination (wire-hanging, rotarod, footprint, and actophotometer tests). Body composition was analyzed in live rats. After that, animals were sacrificed, and serum and gastrocnemius (GN) muscles were collected. Endpoints include myofibrillar protein content, muscle oxidative stress and antioxidants, serum pro-inflammatory cytokines (interleukin-1ß, interleukin-2, and interleukin-6), serum muscle markers (myostatin, creatine kinase, and testosterone), histopathology, and muscle 1H NMR metabolomics. Findings showed that SLB treatment significantly improved muscle strength and muscle coordination, as well as increased lean muscle mass in diabetic rats. Increased pro-inflammatory cytokines and muscle markers (myostatin, creatine kinase) indicate muscle deterioration in diabetic rats, while SLB intervention restored the same. Also, Feret's diameter and cross-sectional area of GN muscle were increased by SLB treatment, indicating the amelioration in diabetic rat muscle. Results of muscle metabolomics exhibit that SLB treatment resulted in the restoration of perturbed metabolites, including histidine-to-tyrosine, phenylalanine-to-tyrosine, and glutamate-to-glutamine ratios and succinate, sarcosine, and 3-hydroxybutyrate (3HB) in diabetic rats. These metabolites showed a pertinent role in muscle inflammation and oxidative stress in diabetic rats. In conclusion, findings showed that salbutamol could be explored as an intervention in diabetic-associated skeletal muscle atrophy.

Impact of sarcosine on diabetic retinopathy: Findings based on weighted gene co-expression network analysis and machine learning techniques.

AIM: To quantify the association between serum sarcosine and diabetic retinopathy (DR) using weighted gene co-expression network analysis (WGCNA). METHODS: We measured serum metabolites in 69 pairs of type 2 diabetes (T2D) patients with and without DR matched by age, gender, body mass index（BMI and HbA1c, using a propensity score matching-based approach. To identify modules and metabolites linked to DR, pathway analysis was performed using WGCNA, the Kyoto Encyclopedia of Genes and Genomes and Small-Molecule Pathway Database. The association of sarcosine with DR was estimated by restricted cubic spline and conditional logistic regression models. Its joint effects with covariates on DR were also extensively examined. RESULTS: With per interquartile range elevation of sarcosine, the adjusted odds ratio (AOR) of DR significantly decreased by 67% (AOR: 0.33, 95% confidence interval [CI]: 0.19-0.58). Similar results were also found in the tertile analysis. Compared with those in the first tertile of sarcosine, the AOR significantly decreased by 54% (AOR: 0.46, 95% CI: 0.18-1.17) and 78% (AOR: 0.22, 95% CI: 0.08-0.59) for subjects in the second and third tertiles, respectively. Compared with subjects with lower sarcosine and lower HDL-C levels, those with higher sarcosine and lower HDL-C levels had the lowest odds of DR (OR: 0.13, 95% CI: 0.04, 0.43). CONCLUSIONS: Serum sarcosine was inversely related to DR, especially in T2D patients with insufficient HDL-C. This study provides insights on a possible novel target for DR precision prevention and control, as well as a better understanding of the DR mechanism.

Point-of-care diagnostics for rapid determination of prostate cancer biomarker sarcosine: application of disposable potentiometric sensor based on oxide-conductive polymer nanocomposite.

One of the most important reasons for an increased mortality rate of cancer is late diagnosis. Point-of-care (POC) diagnostic sensors can provide rapid and cost-effective diagnosis and monitoring of cancer biomarkers. Portable, disposable, and sensitive sarcosine solid-contact ion-selective potentiometric sensors (SC-ISEs) were fabricated as POC analyzers for the rapid determination of the prostate cancer biomarker sarcosine. Tungsten trioxide nanoparticles (WO3 NPs), polyaniline nanoparticles (PANI NPs), and PANI-WO3 nanocomposite were used as ion-to-electron transducers on screen-printed sensors. WO3 NPs and PANI-WO3 nanocomposite have not been investigated before as ion-to-electron transducer layers in potentiometric SC sensors. The designated sensors were characterized using SEM, XRD, FTIR, UV-VIS spectroscopy, and EIS. The inclusion of WO3 and PANI in SC sensors enhanced the transduction at the interface between the screen-printed SC and the ion-selective membrane, offering lower potential drift, a longer lifetime, shorter response time, and better sensitivity. The proposed sarcosine sensors exhibited Nernstian slopes over linear response ranges 10-3-10-7 M, 10-3-10-8 M, 10-5-10-9 M, and 10-7-10-12 M for control, WO3 NPs, PANI NPs, and PANI-WO3 nanocomposite-based sensors, respectively. From a comparative point of view between the four sensors, PANI-WO3 nanocomposite inclusion offered the lowest potential drift (0.5 mV h-1), the longest lifetime (4 months), and the best LOD (9.95 × 10-13 M). The proposed sensors were successfully applied to determine sarcosine as a potential prostate cancer biomarker in urine without prior sample treatment steps. The WHO ASSURED criteria for point-of-care diagnostics are met by the proposed sensors.