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Objective: Cysteamine, a drug approved to treat cystinosis, has been proposed as a host-directed therapy for M. tuberculosis (Mtb) and SARS-CoV-2. The impact of cysteamine on the immune responses has not been fully investigated. We aimed to in vitro evaluate the immunomodulatory effects of cysteamine on peripheral blood mononuclear cells (PBMCs) using the purified protein derivative (PPD) as a recall antigen, and an unspecific stimulus as staphylococcal enterotoxin B (SEB). Methods: PBMCs isolated from subjects with tuberculosis infection (TBI), those with tuberculosis disease (TB), and healthy controls (HC) were in vitro stimulated with PPD or SEB and treated or not with cysteamine at different concentrations (50 µM–400 µM) for 6 hours (h) and 24 h. We evaluated the T helper1 (Th1) and T cytotoxic1 (Tc1) cell cytokine production by flow cytometry and immune-enzymatic assays. In HC, we also evaluated apoptosis and/or necrosis by flow cytometry. Results: We observed an immunomodulatory effect of cysteamine at 400 µM in PBMCs from TB and TBI subjects. It significantly reduced PPD-specific Th1 responses at 24 h and at 6 h (p=0.0004 and p=0.0009, respectively), and a similar non-significant trend was observed with cysteamine at 200 µM (p=0.06 at 24 h and p=0.14 at 6 h). Moreover, cysteamine at both 400 µM (p<0.0001 and p=0.0187 at 24 h, respectively, and p<0.0001 at 6 h for both) and 200 µM (p=0.0119 and p=0.0028 at 24 h and p=0.0028 and p=0.0003 at 6 h, respectively) significantly reduced SEB-induced Th1 and Tc1 responses. Furthermore, we found that cysteamine induced morphological lymphocyte changes and significantly reduced the lymphocyte percentage in a dose- and time-dependent manner. Cysteamine at 400 µM induced 8% late apoptosis and 1.6% necrosis (p<0.05) at 24 h. In contrast, despite significant differences from untreated conditions (p<0.05), cysteamine at 400 µM for 6 h induced approximately 1% late apoptosis and 0.1% necrosis in the cells. Conclusions: High doses of cysteamine in vitro reduce the percentages of PPD- and SEB-induced Th1 and Tc1 cells and induce late apoptosis and necrosis. Differently, cysteamine at lower doses retains the immunomodulatory effect without affecting cell viability. These findings suggest cysteamine as a potential adjunct to antimicrobial regimens as in the TB or COVID-19 field, for its ability to reduce the inflammatory status. [ABSTRACT FROM AUTHOR]

The current work reports a novel approach for the development of an electrochemical sensor based on Ni and Mg-co-doped ZnO nanoparticles (ZNMO) to detect and quantify cysteamine (CA). The chemical co-precipitation strategy was used to synthesize zinc oxide co-doped with magnesium and nickel which can be used as a catalyst material. FTIR, XRD, XPS, BET and SEM-EDX examinations were used to confirm the produced material. The surface of the glassy carbon electrode (GCE) was modified with ZNMO nanoparticles, resulting in a remarkable improvement in the surface area of the electrodes which in turn improved the response for CA compared to previously reported studies. This enhancement can be attributed to the superior catalytic activity of the material in electro-oxidizing CA. The electrochemical studies were carried out using the analytical techniques like cyclic voltammetry and differential pulse voltammetry using 0.1 M phosphate buffer saline as a supporting medium. This fabricated sensor, ZNMO nanoparticles modified GCE (ZNMO/GCE) has shown superior sensing characteristics, including high selectivity, sensitivity, stability, and repeatability, for the identification and quantification of CA. The sensor successfully confirmed the diffusion-controlled electrode technique. It exhibited the widest linear range, spanning from 1 nM to 2500 μM, which is the most impressive result ever reported. The limit of detection (LOD) was determined to be 0.75 nM. Additionally, at the developed sensor, a real-sample analysis was conducted using biological fluids. Hence, the fabricated ZNMO/GCE showed excellent electrocatalytic performance for CA sensing, making it suitable for real-time monitoring. [Display omitted] [ABSTRACT FROM AUTHOR]

Ensuring clean water sources is pivotal for sustainable development and the well-being of communities worldwide. This study represents a pioneering effort in water purification, exploring an innovative approach utilizing modified reduced graphene oxide (rGO) aerogels. These advanced materials promise to revolutionize environmental remediation efforts, specifically removing organic contaminants from aqueous solutions. The study investigates the exceptional adsorption properties of rGO-aerogel, enhanced with cysteamine, to understand its efficacy in addressing water pollution challenges. The characterization methods utilized encompass various analytical techniques, including FE-SEM, BET, FTIR, TGA, DSC, XPS, NMR, and elemental analysis. These analyses provide valuable insights into the material's structural modifications and surface chemistry. The research comprehensively explores the intricacies of adsorption kinetics, equilibrium, and isothermal study to unravel the underlying mechanisms governing contaminant removal. MO and Ni2+ exhibited adsorption of 542.6 and 150.6 mg g−1, respectively, at 25 °C. Ni2+ has unveiled the highest removal at pH 5, and MO has shown high removal in a wide pH range (pH 4–7). Both contaminants have shown fast adsorption kinetic performance on an rGO-aerogel surface. This study aims to identify the synergistic effect of cysteamine and rGO in aerogel formation to remove heavy metals and organic contaminants. These findings mark a significant stride in advancing sustainable water-treatment methods and pioneering in synthesizing innovative materials with versatile applications in environmental contexts, offering a potential solution to the global water pollution crisis. [ABSTRACT FROM AUTHOR]

Background: Salmonella, is one of the most important pathogens causing foodborne illnesses worldwide. The early detection of Salmonella is essential to minimize the risk. Herein, the nanoprobe (CS-AuNPs@phage-T156) for Salmonella was obtained by functionalizing cysteamine (CS) stabilized gold nanoparticles (CS-AuNPs) with phage T156. Results: In the presence of target Salmonella, the CS-AuNPs@phage-T156 specifically recognized and adsorbed on the surface of Salmonella, then induced the aggregation of gold nanoparticles and the color changes from red to purple, which enabled visual detection. The concentration of Salmonella was quantified by the absorption ratio (A680/A526), with a wide linear range from 1.2 × 101 CFU/mL to 1.2 × 106 CFU/mL. Under the optimal experimental conditions, this assay possessed a potent selectivity characteristic quickly toward Salmonella, with a detection limit of 12 CFU/mL. Conclusion: This simple and rapid detection method is expected to provides a novel identification element for the detection of Salmonella by intuitive visualization judgment and quantitative analysis. [ABSTRACT FROM AUTHOR]

There are significant psychosocial burdens in patients with hyperpigmentation, which emphasizes the importance of treatment. Current gold standard for treatment is hydroquinone; however, alternatives have been developed given the concern for side effects of hydroquinone. Melanogenesis is responsible for the production of eumelanin and pheomelanin; there are many factors that will determine whether eumelanin or pheomelanin will be produced. Eumelanin is known for its photoprotective qualities, while pheomelanin is implicated in photocarcinogenesis and photoaging. Multiple treatment modalities for hyperpigmentation that shift eumelanin to pheomelanin synthesis exist. Cysteamine, glutathione, kojic acid, and methyl sulfonyl methane are four agents used to treat hyperpigmentation by shifting the production of eumelanin to pheomelanin. It is critical to discuss photoprotection with patients to help reduce the potential impact of increased pheomelanin production and to expand research in this area. [ABSTRACT FROM AUTHOR]

The work presented here investigates whether the TpMesFe+ moiety, which had been previously found to mediate the dioxygenation of cysteine and cysteamine, can do the same with simple thiols, which are not functionalized by an amine group. Accordingly, the complexes TpMesFeSR (R=Ph, iPr) were synthesized and after full characterization exposed to O2. They were found to react unselectively to yield sulfinates, disulfides, and thiosulfones as products. The sulfinate complex TpMesFeO2S‐p‐Tol was prepared independently and found to be air‐stable, suggesting that the additional products are not formed via overoxidation or subsequent reactions of coordinated sulfinate product. To investigate whether the larger reaction space, opened up due to the missing amine donor is responsible, a Tp‐ligand functionalized by a pyridyl donor was employed. A corresponding Tp‐iron(II) chlorido complex was prepared and converted through salt metathesis reactions into the respective thiolate analogues, which were fully characterized and structurally authenticated. However, subsequent O2 reactivity studies did not show an improved selectivity. The reason may lie in a more open reaction pocket in combination with an electronic situation which is less ideal than in case of TpMesFe(cysteamine). [ABSTRACT FROM AUTHOR]

Sperm cryopreservation in small ruminant is an efficient strategy to distribute spermatozoa for reproductive programmes, but this process reduces the fertility potential of frozen–thawed spermatozoa. The aim of the current research was to evaluate the impact of different concentrations of cysteamine (CYS) in soybean lecithin (SL)‐based medium on postthawed buck semen quality and fertility potential. Semen samples were collected from five bucks, twice a week, then diluted in the SL‐based extender containing different concentrations of CYS as follows: extender containing 0 mM (control, C0), 1 mM (C1), 2 mM (C2), 4 mM (C4) and 8 mM (C8) CYS. Motility characteristics, membrane integrity, abnormal morphology, mitochondrial activity, acrosome integrity, viability, apoptotic‐like changes, lipid peroxidation, DNA fragmentation, ROS concentration, pregnancy rate and kidding rate were evaluated after freeze–thaw process. In results, C1 resulted in greater (p ≤ 0.05) total motility, progressive motility, average path velocity, membrane integrity, mitochondrial activity, acrosome integrity, viability, pregnancy rate and kidding rate compared to the other groups. Furthermore, supplementation of freezing medium with 1 mM of CYS presented lower (p ≤ 0.05) apoptotic‐like changes, lipid peroxidation, DNA fragmentation and ROS concentration compared to the other groups. On the other hand, C8 presented the least (p ≤ 0.05) total motility, progressive motility, average path velocity, membrane integrity, mitochondrial activity, acrosome integrity and viability as well as the highest (p ≤ 0.05) apoptotic‐like changes, lipid peroxidation, DNA fragmentation and ROS concentration compared to the other groups. Therefore, supplementation of freezing medium with 1 mM CYS could be a helpful strategy to protect buck's spermatozoa quality and fertility potential during cryopreservation process. [ABSTRACT FROM AUTHOR]

Cystinosis is a rare autosomal-recessive lysosomal storage disease that progressively affects multiple organs beginning with the kidneys. Patients require lifelong multidisciplinary care for the management of kidney disease and progressive extra-renal manifestations, and thus, they are especially fragile and vulnerable during transition from pediatric to adult care. Previous documents have provided guidance to help the medical transition of these highly burdened patients. Patients and their families often experience great psychological distress and face significant social challenges; for these reasons, they often need help from psychologists, social workers, and other psychosocial professionals. Due to the rarity of the disease, most psychosocial professionals have no expertise in this disorder and require advice. To this end, a steering committee (SC) composed of six experts, including pediatric nephrologists, psychologists, and social workers with experience in the care for patients with cystinosis, have identified and addressed seven key questions related to psychosocial challenges of the disease and the burden of treatment. Ten additional international experts (the extended faculty, EF) were invited to answer these questions. Since robust evidence is lacking, as in many rare diseases, conclusions were based on collective agreement between members of the SC and the EF, and the consolidated answers were summarized into expert opinion statements. The present document contains information on the concerns and psychosocial burden of patients with cystinosis and of their caregivers, and provides practical advice for timely and appropriate support to facilitate the transition to adult care. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) sequelae, such as vomiting, hyperacidity, dysphagia, dysmotility, and diarrhea, are nearly universal among patients with nephropathic cystinosis. These complications result from disease processes (e.g., kidney disease, cystine crystal accumulation in the GI tract) and side effects of treatments (e.g., cysteamine, immunosuppressive therapy). GI involvement can negatively impact patient well-being and jeopardize disease outcomes by compromising drug absorption and patient adherence to the strict treatment regimen required to manage cystinosis. Given improved life expectancy due to advances in kidney transplantation and the transformative impact of cystine-depleting therapy, nephrologists are increasingly focused on addressing extra-renal complications and quality of life in patients with cystinosis. However, there is a lack of clinical data and guidance to inform GI-related monitoring, interventions, and referrals by nephrologists. Various publications have examined the prevalence and pathophysiology of selected GI complications in cystinosis, but none have summarized the full picture or provided guidance based on the literature and expert experience. We aim to comprehensively review GI sequelae associated with cystinosis and its treatments and to discuss approaches for monitoring and managing these complications, including the involvement of gastroenterology and other disciplines. [ABSTRACT FROM AUTHOR]

Despite the direct, redox-free and simple detection non-faradaic impedimetric biosensors offer, considerable optimizations are required to enhance their performance for the detection of various biomarkers. Non-faradaic EIS sensors' performance depends on the interfacial capacitance between a polarized biosensor surface and the tested sample solution. Careful engineering and design of the interfacial capacitance is encouraged to magnify the redout signal upon bioreceptor–antigen interactions. One of the methods to achieve this goal is by optimizing the self-assembled monolayer concentration, which has not been reported for non-faradaic impedimetric sensors. Here, the impact of alkanethiolate (cysteamine) concentration on the performance of gold (Au) interdigitated electrode (Au-IDE) biosensors is reported. Six sets of biosensors were prepared, each with a different cysteamine concentration: 100 nM, 1 μM, 10 μM, 100 μM, 1 mM, and 10 mM. The biosensors were prepared for the direct detection of LDL cholesterol by attaching LDL antibodies on top of the cysteamine via a glutaraldehyde cross-linker. As the concentration of cysteamine increased from 100 nM to 100 μM, the sensitivity of the biosensor increased from 6.7 to 16.2 nF/ln (ng/mL). As the cysteamine concentration increased from 100 μM to 10 mM, the sensitivity deteriorated. The limit of detection (LoD) of the biosensor improved as the cysteamine increased from 100 nM to 100 μM (i.e., 400 ng/mL to 59 pg/mL). However, the LoD started to increase to 67 pg/mL and 16 ng/mL for 1 mM and 10 mM cysteamine concentrations, respectively. This shows that the cysteamine concentration has a detrimental effect on redox-free biosensors. The cysteamine layer has to be as thin as possible and uniformly cover the electrode surfaces to maximize positive readout signals and reduce negative signals, significantly improving both sensitivity and LoD. [ABSTRACT FROM AUTHOR]

Background: Cystinosis is an autosomal recessive lysosomal storage disorder caused by cystine crystals accumulation within lysosomes resulting in multi-organ dysfunction. Infantile nephropathic cystinosis is the most common phenotype of the disease. Cystinosis distal myopathy was first described in 1994 with a 24% prevalence in cystinosis adult patients. Methods: We prospectively evaluated the clinical, biochemical, and radiological data of 22 nephropathic cystinosis pediatric patients from 19 unrelated families (17 males and 5 females, their ages 105.7 ± 41.5 months) recruited at the cystinosis clinic at Cairo University Children's Hospital. Biochemical assessment included several inflammatory biomarkers, such as CRP, ESR, chitotriosidase, and galectin-3. We further performed conventional MRI for the muscles of both upper and lower limbs for potential detection of early myopathic involvement. We compared these findings with 44 CKD children as pathological controls and 22 healthy pediatric controls. Results: Clinically, no evidence of neuromuscular involvement was detected in our cystinosis pediatric cohort. Chitotriosidase was elevated significantly in cystinosis patients compared to CKD controls. Regarding MRI, morphologically, there were no significant differences between the muscles of cystinosis patients and healthy controls. Conclusion: A significantly higher chitotriosidase activity in cystinosis patients seems to better represent the overall disease burden and cannot be linked to neuromuscular involvement. MRI findings in muscles of the cystinosis cohort are not striking and indicate no early changes at a younger age. Follow-up and further studies for higher age groups are required to accurately elucidate the MRI's role in assessing cystinosis myopathy. [ABSTRACT FROM AUTHOR]

Formaldehyde (HCHO) is a human toxin that is both a pollutant and endogenous metabolite. HCHO concentrations in human biological samples are reported in the micromolar range; however, accurate quantification is compromised by a paucity of sensitive analysis methods. To address this issue, we previously reported a novel SPME–GC–MS-based HCHO detection method using cysteamine as an HCHO scavenger. This method showed cysteamine to be a more efficient scavenger than the widely used O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine, and enabled detection of aqueous HCHO in the nanomolar range and quantification in the micromolar range. However, quantification in this range required immersive extraction of the HCHO-derived thiazolidine, while a high background signal was also observed. Following on from these studies, we now report an optimised head-space extraction SPME–GC–MS method using cysteamine, which provides similarly sensitive HCHO quantification to the immersive method but avoids extensive wash steps and is therefore more amenable to screening applications. However, high background HCHO levels were still observed A Complementary GC–MS analyses using a 2-aza-Cope-based HCHO scavenger also revealed high background HCHO levels; therefore, the combined results suggest that HCHO exists in high (i.e. micromolar) concentration in aqueous samples that precludes accurate quantification below the micromolar range. This observation has important implications for ongoing HCHO quantification studies in water, including in biological samples. [ABSTRACT FROM AUTHOR]

Background: Few studies have assessed patient-reported experience measures in nephropathic cystinosis. This study uses patient reports focused on the impact of cystinosis, cysteamine treatment-associated problems, and therapeutic adherence and suggests potential actions for improvement. Methods: In March 2022, six patients with nephropathic cystinosis treated with cysteamine, aged between 12 and 40 years as well as two caregivers, underwent standardized online interviews. Further, in April 2022, two online workshops were organized, each one with the participation of an advisory board consisting of up to four patients and six caregivers. As a result, the first patient journey mapping was developed considering pre-diagnosis, diagnosis and post-diagnosis steps, prescription of treatment, laboratory tests and daily life for patients, categorized by age (children, teenagers, adults). A patient support programme was also considered. Results: Patients were not completely aware of the risks associated with non-adherence. The main factors explaining poor adherence were impaired sleep and chronic fatigue, both related to cysteamine night dosing and prominent gastrointestinal symptoms. These factors have a negative impact on the daily lives of patients. Opportunities for improvement in disease management and therapeutic adherence in nephropathic cystinosis were highlighted. Consequently, a series of lines of action and suggestions were made. Conclusion: This qualitative study offers insights on nephropathic cystinosis from the point of view of patients and parents/caregivers. The critical steps during patient journey and the pitfalls for therapeutic adherence have been highlighted, opening ways to improve not only disease management but also the quality of life of patients with cystinosis. A lay summary is provided as supplementary material; available at: https://www.drugsincontext.com/wp-content/uploads/2024/10/dic.2024-7-1-Suppl-Lay-Summary.pdf

Background: The mainstay of treatment for melasma is topical hydroquinone or preparations containing hydroquinone. In recent years, cysteamine cream has gained popularity in the treatment of hyperpigmentation disorders. Objectives: This study aimed to compare the efficacy of combined hydroquinone/betamethasone to cysteamine in the treatment of melasma. Methods: Eighteen patients had completed this open-label controlled trial. Subjects received either 5% cysteamine cream or a combination of 4% hydroquinone cream and 0.06% betamethasone valerate for 12 weeks according to standardized protocols. Patients were assessed at recruitment, 4 weeks, and 12 weeks after treatment for Melasma Area and Severity Index (MASI) scores. Other parameters relating to skin complexions and patient satisfaction were also assessed. Results: Patients treated with hydroquinone (n = 7) and cysteamine (n = 11) both showed significant decreases in MASI score at week 12: 33.1% (P = 0.009) and 37.9% (P = 0.009), respectively. There was no statistically significant difference between the two treatment groups (P = 0.236). Melanin content at week 12 decreased by 8.8% (P = 0.016) in the hydroquinone group and 11.5% (P = 0.046) in the cysteamine group, with no significant difference between the groups (P = 0.253). No significant differences were observed between the groups for other parameters or patient satisfaction. Conclusion: Cysteamine cream may provide an alternative treatment option for individuals with melasma, offering fewer side effects while delivering comparable results.

Abstract Background Cystinosis is an autosomal recessive lysosomal storage disorder caused by cystine crystals accumulation within lysosomes resulting in multi-organ dysfunction. Infantile nephropathic cystinosis is the most common phenotype of the disease. Cystinosis distal myopathy was first described in 1994 with a 24% prevalence in cystinosis adult patients. Methods We prospectively evaluated the clinical, biochemical, and radiological data of 22 nephropathic cystinosis pediatric patients from 19 unrelated families (17 males and 5 females, their ages 105.7 ± 41.5 months) recruited at the cystinosis clinic at Cairo University Children’s Hospital. Biochemical assessment included several inflammatory biomarkers, such as CRP, ESR, chitotriosidase, and galectin-3. We further performed conventional MRI for the muscles of both upper and lower limbs for potential detection of early myopathic involvement. We compared these findings with 44 CKD children as pathological controls and 22 healthy pediatric controls. Results Clinically, no evidence of neuromuscular involvement was detected in our cystinosis pediatric cohort. Chitotriosidase was elevated significantly in cystinosis patients compared to CKD controls. Regarding MRI, morphologically, there were no significant differences between the muscles of cystinosis patients and healthy controls. Conclusion A significantly higher chitotriosidase activity in cystinosis patients seems to better represent the overall disease burden and cannot be linked to neuromuscular involvement. MRI findings in muscles of the cystinosis cohort are not striking and indicate no early changes at a younger age. Follow-up and further studies for higher age groups are required to accurately elucidate the MRI’s role in assessing cystinosis myopathy.

Cysteamine (CA) induces duodenal ulcers in rodents (Selye and Szabo, Nature 244:458–459, 1973). Cysteine (Cys), a precursor for the formation of CA (via catabolism of coenzyme A), does not cause lesions in the duodenum (Szabo et al., J Pharmacol Exp Ther 223:68–76, 1982). CA also has antimutagenic and anticancer pharmacology (Fujisawa et al., PLoS ONE 7, 2012; Lee, Adv Pharmacol Pharm Sci 2023:2419444, 2023). We propose a mechanism of CA-induced cell death dependent on oxygen and CA dioxygenase (ADO) that can explain the 50-year-old mystery as to why CA is, but Cys is not, ulcerogenic. Those cells expressing coenzyme A-catabolizing enzymes are subject to a unique type of oxygen- and enzyme-bound-Fe2+-dependent death, type II ferroptosis. [ABSTRACT FROM AUTHOR]

Abstract Background Cystinosis is a lysosomal storage disorder characterized by an autosomal recessive phenotype. Intermediate cystinosis, which progresses slowly and causes renal failure, accounts for approximately 5% of all cystinosis cases. Patients with intermediate cystinosis may not exhibit the typical symptoms of cystinosis, such as Fanconi syndrome and ocular symptoms. Because of its diverse clinical presentation and rarity, intermediate cystinosis can be difficult to diagnose. Additionally, few patients can tolerate cystine-depleting drugs, such as cysteamine, because of their complicated administration schedules and side effects. We report a case of intermediate cystinosis that was treated with cysteamine for 10 years. Case presentation Urinary abnormalities were first diagnosed when the patient was 3 years of age during a health examination specifically for 3-year-old children, which is unique to Japan. Cystinosis was diagnosed when the patient was 12 years of age. Cysteamine therapy was initiated and regular cystine concentration measurements were performed. Although proteinuria persisted, the patient’s renal function progressed slowly. Two renal biopsies were performed, and multinucleated podocytes and cystine crystals without focal segmental glomerulosclerosis lesions were observed in the biopsy specimens. The patient’s renal function remained stable. Conclusions This case of intermediate cystinosis was treated with cysteamine over the course of 10 years. Intermediate cystinosis requires an appropriate diagnosis and long-term treatment.

Background: Cystinosis is a lysosomal storage disorder characterized by an autosomal recessive phenotype. Intermediate cystinosis, which progresses slowly and causes renal failure, accounts for approximately 5% of all cystinosis cases. Patients with intermediate cystinosis may not exhibit the typical symptoms of cystinosis, such as Fanconi syndrome and ocular symptoms. Because of its diverse clinical presentation and rarity, intermediate cystinosis can be difficult to diagnose. Additionally, few patients can tolerate cystine-depleting drugs, such as cysteamine, because of their complicated administration schedules and side effects. We report a case of intermediate cystinosis that was treated with cysteamine for 10 years. Case presentation: Urinary abnormalities were first diagnosed when the patient was 3 years of age during a health examination specifically for 3-year-old children, which is unique to Japan. Cystinosis was diagnosed when the patient was 12 years of age. Cysteamine therapy was initiated and regular cystine concentration measurements were performed. Although proteinuria persisted, the patient's renal function progressed slowly. Two renal biopsies were performed, and multinucleated podocytes and cystine crystals without focal segmental glomerulosclerosis lesions were observed in the biopsy specimens. The patient's renal function remained stable. Conclusions: This case of intermediate cystinosis was treated with cysteamine over the course of 10 years. Intermediate cystinosis requires an appropriate diagnosis and long-term treatment. [ABSTRACT FROM AUTHOR]

Cystinosis is a rare autosomal recessive disorder in which cystine crystals accumulate within the cellular lysosomes, causing damage to multiple organs. Due to challenges with the stringent cysteamine treatment regimen and side effects, adherence is often sub-optimal. This study aimed to assess the level of adherence to cysteamine therapy among cystinosis patients in Saudi Arabia and its impact on their quality of life. Electronic medical record data of 39 cystinosis patients from the Department of Nephrology at King Faisal Specialist Hospital and Research Center in Saudi Arabia were reviewed, and 25 patients were included in this study. Out of the 25 patients included in the final analysis, 64% (n = 16) were female. The mean age was 19.04 years. Almost all patients (23/25, 92%) were on oral IR cysteamine therapy, and 52% (13/25) were on topical cysteamine eye drop treatment. Of the 15 patients who responded to the Morisky Medication Adherence Scale-8 (MMAS-8) questionnaire, only 4 (26.7%) were highly adherent to cysteamine therapy. Most of the respondents (7/15, 46.7%) showed a medium level of treatment adherence. Based on the medication possession ratio for oral cysteamine, only 6 out of 23 patients (26.1%) were found to be 96–100% adherent. For the cysteamine eye drops, only 5/13 patients (38.4%) were 76–95% adherent. The 36-Item Short Form Health Survey (SF-36) used to assess patients' health-related outcomes showed that their quality of life was affected in the domains of 'social functioning' and 'energy/fatigue.' Despite a small sample size, this study shows sub-optimal adherence to cysteamine treatment in patients from Saudi Arabia. The possible reasons for low treatment adherence could be a high frequency of administration and treatment-related side effects. [ABSTRACT FROM AUTHOR]

Onopordopicrin (OPP), found in burdock leaves and stems, exerts antiallergic properties whose mechanism remains elusive. We aimed to elucidate its mechanism using rat basophilic leukemia cells in vitro. Purified OPP demonstrated concentration‐dependent inhibition of degranulation after allergen or PMA/A23187 stimulation. OPP effectively suppressed TNF‐α and PGD2 releases. However, OPP did not suppress the increase in intracellular Ca2+ concentration after allergen stimulation. The α, β‐unsaturated carbonyl structure of OPP suggests potential electrophilic reactivity with polyfunctional thiol‐trapping agents, such as cysteine residues. Indeed, the degranulation‐inhibiting effect of OPP disappeared with the addition of cysteamine, which possesses a thiol group. I kappa B kinase β (IKKβ), which regulates degranulation in an NF‐κB‐independent manner, possesses a cysteine residue between the activation loop. Moreover, IKKβ plays an important role in TNF‐α and PGD2 production. OPP was found to reduce IKKβ activity in a concentration‐dependent manner. Together, our findings suggest that OPP exerts its antiallergic action via binding to cysteine residues in signal proteins such as IKKβ, thereby inhibiting their activation. [ABSTRACT FROM AUTHOR]

Cystinosis is a rare autosomal recessive disease characterised by an accumulation of cystine in the lysosomes. It is caused by pathogenic variants of the cystinosin gene (CTNS), which interrupts the transport of cystine from the lysosomes into the cytosol. Intra-lysosomal cystine accumulation leads to subsequent cellular dysfunction. Cystinosis has an incidence of 0.5–1/100,000 live births. There are three forms of cystinosis: nephropathic cystinosis, juvenile cystinosis, and ocular cystinosis, with nephropathic cystinosis being the most prevalent disease subtype. Renal impairment is the most common manifestation of disease. Extrarenal manifestations of cystinosis include hypothyroidism, diabetes, and hypogonadism. The current treatment for cystinosis is cysteamine, a cystine-depleting agent. This is not a curative treatment and only aims to slow the progression of disease. A total of 90% of cystinosis patients progress to kidney failure within the first 20 years of life. Kidney transplantation is the only option available to patients once the disease has progressed to this stage. This review highlights the pathogenesis and clinical manifestations of cystinosis, as well as potential future treatment options. [ABSTRACT FROM AUTHOR]

Simple Summary: Cysteamine, an endogenously synthesized agent in mammalian cells and FDA-approved for cystinosis, shows promise as a safe anti-cancer agent by inhibiting tumor cell invasion and metastasis. Using computational analyses and multiple glioblastoma cell lines, we demonstrate the in vitro drug efficacy and molecular mechanism by which cysteamine inhibits tumor invasion and migration through targeting matrix metalloproteinase activity at micromolar concentrations. Our findings suggest that cysteamine could represent a novel therapeutic option for the treatment of glioblastoma patients. Glioblastoma (GBM) cells are highly invasive, infiltrating the surrounding normal brain tissue, thereby limiting the efficacy of surgical resection and focal radiotherapy. Cysteamine, a small aminothiol molecule that is orally bioavailable and approved for cystinosis, has potential as a cancer treatment by inhibiting tumor cell invasion and metastasis. Here we demonstrate that these potential therapeutic effects of cysteamine are likely due to the inhibition of matrix metalloproteinases (MMPs) in GBM. In vitro assays confirmed that micromolar concentrations of cysteamine were not cytotoxic, enabling the interrogation of the cellular effects without confounding tumor cell loss. Cysteamine's inhibition of MMP activity, especially the targeting of MMP2, MMP9, and MMP14, was observed at micromolar concentrations, suggesting the mechanism of action in suppressing invasion and cell migration is by inhibition of these MMPs. These findings suggest that achievable micromolar concentrations of cysteamine effectively inhibit cancer cell invasion and migration in GBM, supporting the potential for use as an adjunct cancer treatment. [ABSTRACT FROM AUTHOR]

ObjectiveCysteamine, a drug approved to treat cystinosis, has been proposed as a host-directed therapy for M. tuberculosis (Mtb) and SARS-CoV-2. The impact of cysteamine on the immune responses has not been fully investigated. We aimed to in vitro evaluate the immunomodulatory effects of cysteamine on peripheral blood mononuclear cells (PBMCs) using the purified protein derivative (PPD) as a recall antigen, and an unspecific stimulus as staphylococcal enterotoxin B (SEB).MethodsPBMCs isolated from subjects with tuberculosis infection (TBI), those with tuberculosis disease (TB), and healthy controls (HC) were in vitro stimulated with PPD or SEB and treated or not with cysteamine at different concentrations (50 µM–400 µM) for 6 hours (h) and 24 h. We evaluated the T helper1 (Th1) and T cytotoxic1 (Tc1) cell cytokine production by flow cytometry and immune-enzymatic assays. In HC, we also evaluated apoptosis and/or necrosis by flow cytometry.ResultsWe observed an immunomodulatory effect of cysteamine at 400 µM in PBMCs from TB and TBI subjects. It significantly reduced PPD-specific Th1 responses at 24 h and at 6 h (p=0.0004 and p=0.0009, respectively), and a similar non-significant trend was observed with cysteamine at 200 µM (p=0.06 at 24 h and p=0.14 at 6 h). Moreover, cysteamine at both 400 µM (p

Cystinosis is an autosomal recessive metabolic disease characterized by lysosomal accumulation of cystine in all the cells of the body. Infantile cystinosis begins in infancy by a renal Fanconi syndrome and eventually leads to multi-organ failure, including the kidney, eye, thyroid, muscle, and pancreas, eventually causing premature death in early adulthood. The current treatment is the drug cysteamine that only delays the progression of the disease. We identified the gene involved, CTNS, and showed that the encoded protein, cystinosin, is a proton-driven cystine transporter. We generated a mouse model of cystinosis, the Ctns-/- mice, that recapitulates the main disease complications. The goal was next to develop a gene therapy approach for cystinosis. We used bone marrow stem cells as a vehicle to bring the healthy CTNS gene to tissues, and we showed that wild-type hematopoietic stem and progenitor cell (HSPC) transplantation led to abundant tissue integration of bone marrow-derived cells, significant decrease of tissue cystine accumulation and long-term kidney, eye and thyroid preservation. We then developed an autologous transplantation approach of HSPCs modified ex vivo using a lentiviral vector to introduce a functional CTNS cDNA, and showed its efficacy in Ctns-/- mice. We conducted the pharmacology/toxicology studies, developed the manufacturing process using human CD34+ cells, and design the clinical trial. We received Food and Drug Administration (FDA)-clearance to start a phase 1/2 clinical trial for cystinosis in December 2018. Six patients have been treated so far. In this review, we describe the path to go from the gene to a gene therapy approach for cystinosis.

Cystinosis is a rare lysosomal storage disorder caused by autosomal recessive mutations in the CTNS gene that encodes for the cystine transporter cystinosin, which is expressed on the lysosomal membrane mediating the efflux of cystine. Cysteamine bitartrate is a cystine-depleting aminothiol agent approved for the treatment of cystinosis in children and adults. In this study, we developed and validated a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for the determination of cysteamine levels in plasma samples. This LC-MS/MS method was validated according to the European Medicines Agency (EMA)'s guidelines for bioanalytical method validation. An ultra-performance liquid chromatograph (UPLC) coupled with a 6470 mass spectrometry system was used for cysteamine determination. Our validated method was applied to plasma samples from n = 8 cystinosis patients (median, interquartile range (IQR) = 20.5, 8.5–26.0 years). The samples were collected before cysteamine oral administration (pre-dose) and 1 h after (post-dose). Our bioanalytical method fulfilled the regulatory guidelines for method validation. The cysteamine plasma levels in pre-dose samples were 2.57 and 1.50–3.31 μM (median and IQR, respectively), whereas the post-dose samples reported a cysteamine median concentration of 28.00 μM (IQR: 17.60–36.61). Our method allows the rapid determination of cysteamine plasma levels. This method was successfully used in cystinosis patients and, therefore, could be a useful tool for the evaluation of therapy adherence and for future pharmacokinetic (PK) studies involving a higher number of subjects. [ABSTRACT FROM AUTHOR]

Background: Melasma is a chronic dermatosis that impacts the patient's quality of life and can present considerable challenges in terms of effective treatment. Objective: To evaluate the effectiveness, tolerability, and safety of 5% cysteamine combined with 4% nicotinamide in female subjects with melasma. Methods: This single‐center, single‐arm, prospective, open‐label study evaluated patients with melasma using a combination cream of 5% cysteamine and 4% nicotinamide in a progressive regimen (60 min in the first month, 120 min in the second month, and 180 min in the third month). Results: Overall, 35 treated subjects exhibited reduced modified Melasma Area and Severity Index (mMASI) (p < 0.001) and decreased MelasQoL scores (p < 0.001), accompanied by improved brightness, luminosity, homogeneity, and spot intensity (p < 0.001). Photographic and colorimetric analysis revealed smaller spots and improved homogeneity. Limitations: Adherence to progressive daily treatment could not be evaluated long‐term. Conclusion: A combination cream comprising 5% cysteamine and 4% nicotinamide was effective, tolerable, and safe for treating melasma. [ABSTRACT FROM AUTHOR]

Riboflavin (RF) and cysteamine (Cys) are vital in clinical and other fields, but their detection is often intricate and reliant on costly equipment and materials. Plasmon-enhanced fluorescence (PEF) using plasmonic nanoparticles offers a solution to enhance the optical properties of fluorophores. Additionally, fluorescence quenching becomes apparent when the distance between the fluorophores and nanostructures shrinks to a few nanometers. Harnessing these effects holds tremendous promise for improved detection performance. In this study, the PEF of RF by Ag@SiO2 nanoparticles was presented and used to improve RF detection. The fluorescence enhancement of RF was "turned off" in the presence of Cys because of the aggregation of Ag@SiO2 nanoparticles caused by Cys, which can be used for the detection of Cys. On the other hand, the quenched fluorescence of RF caused by small Ag nanoparticles was "turned on" in the presence of Cys, which can further realize the detection of Cys with lower concentrations. Additionally, the color of the Ag NPs-RF composites changed in the presence of Cys, which can also be used for the colorimetric detection of Cys. A minimum detected concentration as low as 16.6 nM was realized by fluorescence and colorimetric dual-mode detection. Depending on the interactions between the plasmonic nanoparticles and Cys, the plasmonic nanoparticles show great potential for the dual-mode detection strategy in the sensitive evaluation of analytes. The dual-mode detection based on the Ag nanoparticles provides the feasibility of the nanoprobe in potential applications, which opens a promising avenue for simple, sensitive, and selective detection. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Postinffammatory hyperpigmentation (PIH) is a common sequela of acne vulgaris. Topical treatment with hydroquinone is the standard treatment, but may be associated with complications. Cysteamine is a relatively safe depigmenting agent with an observed depigmenting effect. We designed this study to assess the efficacy of a cysteamine 5% cream in treating acne-induced PIH. METHODS: Twenty-eight out of 32 participants finalized this investigator-blind, randomized, and controlled trial (registered in Iranian Registry of Clinical Trials [IRCTID: IRCT20140212016557N5]). We randomized the patients to apply either cysteamine 5% or hydroquinone 4%/ascorbic acid 3% (HC) cream. Postacne hyperpigmentation index (PAHPI) and melanin index were the assessment measures after four months of treatment. We evaluated the quality of life by the Dermatology Life Quality Index (DLQI) questionnaire. RESULTS: Both cysteamine and HC cream significantly decreased the PAHPI score and melanin index of acne-induced PIH patients (p<0.05). The decrease in PAHPI score and melanin index were not significantly different in treatment groups after four months (p>0.05). Quality of life ameliorated significantly only with cysteamine treatment. However, no significant change in quality of life was observed between groups. LIMITATIONS: Limitations of our study include the relatively small sample size and absence of follow-up. CONCLUSION: Cysteamine cream is an effective treatment of post-acne PIH, with similar efficacy to the accepted treatment of PIH, i.e., hydroquinone cream. [ABSTRACT FROM AUTHOR]

Background The purpose of this study is to evaluate the effectiveness and safety of switching from immediate-release (IR) to extended-release (ER) cysteamine in patients with nephropathic cystinosis (NC) in Spain. Methods We conducted an observational, retrospective, multicentre study in NC patients who received IR cysteamine for at least 12 months, switched to ER cysteamine, and received it for at least 6 months before inclusion. Results Data were collected from nine patients (four children, five adults) 36 months before and after the switch. Despite the highly selected population, an improvement in growth, particularly in children and a significant reduction in hospitalization days was observed. A decrease in halitosis, body odour and gastrointestinal effects was reported in most of the patients who suffered before the switch, and the use of proton pump inhibitors (PPIs) decreased in some patients. The estimated glomerular filtration rate (eGFR) remained stable in patients with preserved kidney function. No significant changes in white blood cell (WBC) cystine levels were observed after the switch. There was no significant difference in the cysteamine dose received. However, some patients were receiving <50% of the recommended dose of cysteamine before and after the switch and showed elevated levels of WBC cystine. Conclusions Switching from IR to ER cysteamine in clinical practice reduces hospital stays, improves nutritional status and growth in paediatric patients and could help to enhance treatment tolerability by reducing side effects. Furthermore, the dosing of ER cysteamine could promote therapeutic compliance and positively affect the quality of life of the NC population. [ABSTRACT FROM AUTHOR]

Glutathione (GSH) is a major endogenous antioxidant, and its depletion has been observed in several brain diseases including epilepsy. Previous studies in our laboratory have shown that dimercaprol (DMP) can elevate GSH via post-translational activation of glutamate cysteine ligase (GCL), the rate limiting GSH biosynthetic enzyme and inhibit neuroinflammation in vitro. Here we determined 1) the role of cysteamine as a new mechanism by which DMP increases GSH biosynthesis and 2) its ability to inhibit neuroinflammation and neuronal injury in the rat kainate model of epilepsy. DMP depleted cysteamine in a time- and concentration-dependent manner in a cell free system. To guide the in vivo administration of DMP, its pharmacokinetic profile was determined in the plasma, liver, and brain. The results confirmed DMP's ability to cross the blood-brain-barrier. Treatment of rats with DMP (30 mg/kg) depleted cysteamine in the liver and hippocampus that was associated with increased GCL activity in these tissues. GSH levels were significantly increased (20 %) in the hippocampus 1 h after 30 mg/kg DMP administration. Following DMP (30 mg/kg) administration once daily, a marked attenuation of GSH depletion was seen in the SE model. SE-induced inflammatory markers including cytokine release, microglial activation, and neuronal death were significantly attenuated in the hippocampus with DMP treatment. Taken together, these results highlight the importance of restoring redox status with rescue of GSH depletion by DMP in post epileptogenic insults.

For sustainable development, better performance, and less gas pollution during rumen fermentation, there is a need to find a green and safe feed additive for ruminants. Cysteamine (CS) is a biological compound naturally produced in mammalian cells. It is widely used as a growth promoter in ruminants because of its ability to control hormone secretions. It mainly controls the circulating concentration of somatostatin and enhances growth hormone production, leading to improved growth performance. CS modulates the rumen fermentation process in a way beneficial for the animals and environment, leading to less methane production and nutrients loss. Another beneficial effect of using CS is that it improves the availability of nutrients to the animals and enhances their absorption. CS also works as an antioxidant and protects the cells from oxidative damage. In addition, CS has no adverse effects on bacterial and fungal alpha diversity in ruminants. Dietary supplementation of CS enhances the population of beneficial microorganisms. Still, no data is available on the use of CS on reproductive performance in ruminants, so there is a need to evaluate the effects of using CS in breeding animals for an extended period. In this review, the action mode of CS was updated according to recently published data to highlight the beneficial effects of using CS in ruminants.

Ensuring clean water sources is pivotal for sustainable development and the well-being of communities worldwide. This study represents a pioneering effort in water purification, exploring an innovative approach utilizing modified reduced graphene oxide (rGO) aerogels. These advanced materials promise to revolutionize environmental remediation efforts, specifically removing organic contaminants from aqueous solutions. The study investigates the exceptional adsorption properties of rGO-aerogel, enhanced with cysteamine, to understand its efficacy in addressing water pollution challenges. The characterization methods utilized encompass various analytical techniques, including FE-SEM, BET, FTIR, TGA, DSC, XPS, NMR, and elemental analysis. These analyses provide valuable insights into the material’s structural modifications and surface chemistry. The research comprehensively explores the intricacies of adsorption kinetics, equilibrium, and isothermal study to unravel the underlying mechanisms governing contaminant removal. MO and Ni2+ exhibited adsorption of 542.6 and 150.6 mg g−1, respectively, at 25 °C. Ni2+ has unveiled the highest removal at pH 5, and MO has shown high removal in a wide pH range (pH 4–7). Both contaminants have shown fast adsorption kinetic performance on an rGO-aerogel surface. This study aims to identify the synergistic effect of cysteamine and rGO in aerogel formation to remove heavy metals and organic contaminants. These findings mark a significant stride in advancing sustainable water-treatment methods and pioneering in synthesizing innovative materials with versatile applications in environmental contexts, offering a potential solution to the global water pollution crisis.

For sustainable development, better performance, and less gas pollution during rumen fermentation, there is a need to find a green and safe feed additive for ruminants. Cysteamine (CS) is a biological compound naturally produced in mammalian cells. It is widely used as a growth promoter in ruminants because of its ability to control hormone secretions. It mainly controls the circulating concentration of somatostatin and enhances growth hormone production, leading to improved growth performance. CS modulates the rumen fermentation process in a way beneficial for the animals and environment, leading to less methane production and nutrients loss. Another beneficial effect of using CS is that it improves the availability of nutrients to the animals and enhances their absorption. CS also works as an antioxidant and protects the cells from oxidative damage. In addition, CS has no adverse effects on bacterial and fungal alpha diversity in ruminants. Dietary supplementation of CS enhances the population of beneficial microorganisms. Still, no data is available on the use of CS on reproductive performance in ruminants, so there is a need to evaluate the effects of using CS in breeding animals for an extended period. In this review, the action mode of CS was updated according to recently published data to highlight the beneficial effects of using CS in ruminants. [ABSTRACT FROM AUTHOR]

Background : Cystinosis is a rare autosomal recessive lysosomal disorder that mainly affects the kidney and eye. Early treatment with cysteamine significantly improves the prognosis. However, early diagnosis of cystinosis, especially the juvenile nephropathic form, remains challenging because typical symptoms only become apparent in adulthood. We herein describe a 13-year-old girl who presented with proteinuria only but was diagnosed with juvenile nephropathic cystinosis based on multinucleated podocytes in her kidney biopsy specimen. We also studied the nephropathology of another case to determine the features of the multinucleated podocytes. Case diagnosis: A previously healthy 13-year-old girl presented to our hospital because proteinuria had been detected in her school urine screening. She had been noted to have proteinuria on her school urine screening when she was 11 years of age but there was no consultation with her physician at that time. She was asymptomatic and had no other abnormalities on examination other than a relatively high urinary β-2 microglobulin level. Her kidney biopsy showed 15 multinucleated podocytes in 34 glomeruli, and the mean number of nuclei per multinucleated podocyte was 4.4. Ophthalmological examination showed cystine crystals in her cornea. Her white blood cell cystine level was high, and she was diagnosed with juvenile nephropathic cystinosis. She started oral cysteamine treatment and showed almost no progression of the disease after 2 years. In another patient with juvenile nephropathic cystinosis, there were 25 multinucleated podocytes in 63 glomeruli, and the mean number of nuclei per multinucleated podocyte was 2.9. Conclusion: Early diagnosis is crucial to improve the prognosis of patients with cystinosis. This report emphasizes the importance of recognizing the unique pathological feature of multinucleated podocytes as an essential clue to the diagnosis of cystinosis. [ABSTRACT FROM AUTHOR]

Cystinosis is a low-prevalence lysosomal storage disease. The pathomechanism involves abnormal functioning of the cystinosine lysosomal cystine transporter (CTNS), causing intraliposomal accumulation of the amino acid cysteine disulfide, which crystallizes and deposits in several parts of the body. The most common ophthalmic complication of cystinosis is the deposition of "gold dust" cystine crystals on the cornea, which already occurs in infancy and leads to severe photosensitivity and dry eyes as it gradually progresses with age. In the specific treatment of cystinosis, preparations containing cysteamine (CYA) are used. The availability of commercialized eyedrops for the targeted treatment is scarce, and only Cystadrops® are commercially available with strong limitations. Thus, magistral CYA-containing compounded eyedrops (CYA-CED) could have a key role in patient care; however, a rationally designed comprehensive study on the commercialized and magistral products is still missing. This work aims to build up a comprehensive study about commercialized and magistral CYA eye drops, involving pharmacokinetic and physicochemical characterization (applying mucoadhesivity, rheology test, investigation of drug release, and parallel artificial membrane permeability assays), as well as ex vivo tests, well supported by statistical analysis. [ABSTRACT FROM AUTHOR]

Background: Solar lentigines are common hyperpigmented lesions typically appearing after 50 years of age and associated with negative psychological effects in affected individuals. Topical depigmenting products, such as hydroquinone and even the Kligman's formula, are usually ineffective for treating lentigines. Stabilized cysteamine has been recently shown to be as effective as the modified Kligman's formula for treating melasma. In this study, we evaluated the therapeutic effect of a stabilized cysteamine on solar lentigines. Methods: A vehicle‐controlled, double‐blind, and randomized study was performed on 30 patients with solar lentigines. Stabilized cysteamine or vehicle control creams were applied on solar lentigines on the dorsum of the hands daily for 12 weeks. Clinical measurements with colorimetry and visual analog scale were performed at baseline, 4, 8, and 12 weeks. Results: Statistically significant results were obtained in the cysteamine group versus the vehicle control group. Stabilized cysteamine provided a 40% reduction in colorimetric values (p < 0.002) versus a 2% reduction in the vehicle group (p < 0.405). Cysteamine also provided a 40% reduction in VAS (p < 0.001) versus a 2% reduction in the vehicle group (p < 0.245). Conclusion: Significant improvement of solar lentigines was observed after 12 weeks of application of stabilized cysteamine by all evaluation methods. Stabilized cysteamine represents a highly effective topical treatment for solar lentigines and can be considered as one of the first topical therapies effective on this hyperpigmentary disorder. [ABSTRACT FROM AUTHOR]

Introduction: Chronic lung infection due to bacterial biofilms is one of the leading causes of mortality in cystic fibrosis (CF) patients. Among many species colonizing the lung airways, Pseudomonas aeruginosa and Staphylococcus aureus are two virulent pathogens involved in mechanically robust biofilms that are difficult to eradicate using airway clearance techniques like lung lavage. To remove such biological materials, glycoside hydrolase-based compounds are commonly employed for targeting and breaking down the biofilm matrix, and subsequently increasing cell susceptibility to antibiotics. Materials and methods: In this study, we evaluate the effects of N-acetyl cysteine (NAC) and Cysteamine (CYST) in disrupting interfacial bacterial films, targeting different components of the extracellular polymeric substances (EPS). We characterize the mechanics and structural integrity of the interfacial bacterial films using pendant drop elastometry and scanning electron microscopy. Results and discussion: Our results show that the film architectures are compromised by treatment with disrupting agents for 6 h, which reduces film elasticity significantly. These effects are profound in the wild type and mucoid P. aeruginosa, compared to S. aureus. We further assess the effects of competition and cooperation between S. aureus and P. aeruginosa on the mechanics of composite interfacial films. Films of S. aureus and wild-type P. aeruginosa cocultures lose mechanical strength while those of S. aureus and mucoid P. aeruginosa exhibit improved storage modulus. Treatment with NAC and CYST reduces the elastic property of both composite films, owing to the drugs' ability to disintegrate their EPS matrix. Overall, our results provide new insights into methods for assessing the efficacy of mucolytic agents against interfacial biofilms relevant to cystic fibrosis infection. [ABSTRACT FROM AUTHOR]

Simple Summary: The in vitro production (IVP) of bovine embryos has increased in popularity in the past few decades with improvements in our ability to harvest oocytes from genetically elite heifers and cows, fertilize them in vitro, and successfully culture embryos to the stage where they can be transferred. One issue with IVP is that the efficiency of embryo production is less than ideal. One likely reason for the poor development of IVP embryos is the excessive exposure of oocytes and embryos to reactive oxygen species (ROS). These molecules are produced as a normal by-product of energy generation; however, excess accumulation of ROS during the IVP of oocyte and embryo culture will damage nucleic acids, lipids, and proteins in ways that compromise development potential and post-transfer embryo survival. Molecules that react with and block ROS-induced damage are commonly referred to as antioxidants. This review explores the use of five common antioxidants to limit ROS-induced damage and promote the IVP of embryos. The in vitro production (IVP) of bovine embryos has gained popularity worldwide and in recent years and its use for producing embryos from genetically elite heifers and cows has surpassed the use of conventional superovulation-based embryo production schemes. There are, however, several issues with the IVP of embryos that remain unresolved. One limitation of special concern is the low efficiency of the IVP of embryos. Exposure to reactive oxygen species (ROS) is one reason why the production of embryos with IVP is diminished. These highly reactive molecules are generated in small amounts through normal cellular metabolism, but their abundances increase in embryo culture because of oocyte and embryo exposure to temperature fluctuations, light exposure, pH changes, atmospheric oxygen tension, suboptimal culture media formulations, and cryopreservation. When uncontrolled, ROS produce detrimental effects on the structure and function of genomic and mitochondrial DNA, alter DNA methylation, increase lipid membrane damage, and modify protein activity. Several intrinsic enzymatic pathways control ROS abundance and damage, and antioxidants react with and reduce the reactive potential of ROS. This review will focus on exploring the efficiency of supplementing several of these antioxidant molecules on oocyte maturation, sperm viability, fertilization, and embryo culture. [ABSTRACT FROM AUTHOR]

Objective To assess the effectiveness of 5% cysteamine serum combined with 3% tranexamic acid cream using layering technique for treatment of melasma. Methods The study design is a pretest-posttest clinical trial conducted at the dermatology outpatient clinic of Hasanuddin University Hospital and Wahidin Sudirohusodo Hospital, Makassar, South Sulawesi, Indonesia from December 2020-December 2021. A total of 40 subjects that met the inclusion criteria participated in the study. Subjects were instructed to cleanse their face at night and apply two drops of 5% cysteamine serum over the face for 15 minutes, followed with application of 1 fingertip unit (FTU) of 3% tranexamic acid cream. Parameters for assessment used in this study are modified melasma severity index (mMASI) score, pigmented facial spots using Janus Skin Analyzer, L* value using Chromameter and Melanin Index (MI) using Mexameter. Results There were significant improvements in all parameters with a mean mMASI score decrease of 0.42 point from 7.97 to 7.55 (p <0.05), decreased pigmented facial spots from 52.29 to 49.17 (p<0.05), an increase of L* value from 46.82 to 50.88 from W0 to W8 using Chromameter® (p<0.05), and a 48.94-point decrease in MI using Mexameter ® from 359.49 to 310.55 (p<0.05). Conclusion Combination of 5% cysteamine serum and 3% tranexamic acid cream using layering technique is a promising combined regiment for treatment of melasma. [ABSTRACT FROM AUTHOR]