Laboratory Diagnosis of Intrathecal Synthesis of Immunoglobulins: A Review about the Contribution of OCBs and K-index.

The diagnosis of MS relies on a combination of imaging, clinical examinations, and biological analyses, including blood and cerebrospinal fluid (CSF) assessments. G-Oligoclonal bands (OCBs) are considered a "gold standard" for MS diagnosis due to their high sensitivity and specificity. Recent advancements have involved the introduced of kappa free light chain (k-FLC) assay into cerebrospinal fluid (CSF) and serum (S), along with the albumin quotient, leading to the development of a novel biomarker known as the "K-index" or "k-FLC index". The use of the K-index has been recommended to decrease costs, increase laboratory efficiency, and to skip potential subjective operator-dependent risk that could happen during the identification of OCBs profiles. This review aims to provide a comprehensive overview and analysis of recent scientific articles, focusing on updated methods for MS diagnosis with an emphasis on the utility of the K-index. Numerous studies indicate that the K-index demonstrates high sensitivity and specificity, often comparable to or surpassing the diagnostic accuracy of OCBs evaluation. The integration of the measure of the K-index with OCBs assessment emerges as a more precise method for MS diagnosis. This combined approach not only enhances diagnostic accuracy, but also offers a more efficient and cost-effective alternative.

Urine Parameters in Patients with COVID-19 Infection.

A urine test permits the measure of several urinary markers. This is a non-invasive method for early monitoring of potential kidney damage. In COVID-19 patients, alterations of urinary markers were observed. This review aims to evaluate the utility of urinalysis in predicting the severity of COVID-19. A total of 68 articles obtained from PubMed studies reported that (i) the severity of disease was related to haematuria and proteinuria and that (ii) typical alterations of the urinary sediment were noticed in COVID-19-associated AKI patients. This review emphasizes that urinalysis and microscopic examination support clinicians in diagnosing and predicting COVID-19 severity.

Contribution of vitamin D3 and thiols status to the outcome of COVID-19 disease in Italian pediatric and adult patients.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), was declared a global pandemic by the World Health Organization (WHO) on March 2020, causing unprecedented disease with million deaths across the globe, mostly adults. Indeed, children accounted for only a few percent of cases. Italy was the first Western country struck by the COVID-19 epidemic. Increasing age, which is one of the principal risk factors for COVID-19 mortality, is associated with declined glutathione (GSH) levels. Over the last decade, several studies demonstrated that both vitamin D (VD) and GSH have immunomodulatory properties. To verify the association between VD, GSH and the outcome of COVID-19 disease, we conducted a multicenter retrospective study in 35 children and 128 adult patients with COVID-19. Our study demonstrated a hypovitaminosis D in COVID-19 patients, suggesting a possible role of low VD status in increasing the risk of COVID-19 infection and subsequent hospitalization. In addition, we find a thiol disturbance with a GSH depletion associated to the disease severity. In children, who fortunately survived, both VD and GSH levels at admission were higher than in adults, suggesting that lower VD and thiols levels upon admission may be a modifiable risk factor for adverse outcomes and mortality in hospitalized patients with COVID-19.

Admission eGFR predicts in-hospital mortality independently of admission glycemia and C-peptide in patients with type 2 diabetes mellitus and COVID-19.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) and impaired kidney function are associated with a higher risk of poor outcomes of coronavirus disease 2019 (COVID-19). We conducted a retrospective study in hospitalized T2DM patients with COVID-19 to assess the association between in-hospital mortality and admission values of different hematological/biochemical parameters, including estimated glomerular filtration rate (eGFR), plasma glucose and C-peptide (the latter serving as a marker of beta-cell function). METHODS: The study included T2DM patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were consecutively admitted to our Institution between 1 October 2020 and 1 April 2021. RESULTS: Patients (n = 74) were categorized into survivors (n = 55) and non-survivors (n = 19). Non-survivors exhibited significantly higher median white blood cell (WBC) count, D-dimer, neutrophil-to-lymphocyte ratio, high-sensitivity C-reactive protein (hsCRP), and procalcitonin levels, as well as significantly lower median serum 25-hydroxyvitamin D [25(OH)D] levels compared to survivors. Non-survivors exhibited significantly higher median admission plasma glucose (APG) values compared to survivors (210 vs. 166 mg/dL; p = .026). There was no statistically significant difference in median values of (random) plasma C-peptide between non-survivors and survivors (3.55 vs. 3.24 ng/mL; p = .906). A significantly higher percentage of patients with an eGFR < 60 mL/min/1.73 m2 was observed in the non-survivor group as compared to the survivor group (57.9% vs. 23.6%; p = .006). A multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, sex, body mass index, major comorbidities) showed a significant inverse association between admission eGFR values and risk of in-hospital mortality (OR, 0.956; 95% CI, 0.931-0.983; p = .001). We also found a significant positive association between admission WBC count and risk of in-hospital mortality (OR, 1.210; 95% CI, 1.043-1.404; p = .011). CONCLUSIONS: Admission eGFR and WBC count predict in-hospital COVID-19 mortality among T2DM patients, independently of traditional risk factors, APG and random plasma C-peptide. Hospitalized patients with COVID-19 and comorbid T2DM associated with impaired kidney function at admission should be considered at high risk for adverse outcomes and death.

Low Vitamin D Status at Admission as a Risk Factor for Poor Survival in Hospitalized Patients With COVID-19: An Italian Retrospective Study.

OBJECTIVE: Preliminary findings suggest a relationship between lower serum 25-hydroxyvitamin D [25(OH)D] levels and incidence and severity of COVID-19. The aim of this study was to evaluate the relationship between vitamin D status at admission and different markers of inflammation, coagulation, and sepsis in hospitalized patients with COVID-19. METHOD: We conducted a retrospective study on 137 consecutive patients with SARS-CoV-2 infection and available data on serum 25(OH)D levels, who were admitted to our Institution between March 1 and April 30, 2020. Patients were divided into two groups: survivors (n = 78; 57%) and non-survivors (n = 59; 43%). RESULTS: At admission, all patients showed hypovitaminosis D. Median total serum 25(OH)D levels at admission were significantly higher in survivors than non-survivors (12 ng/mL vs 8 ng/mL; p < 0.01). Non-survivors exhibited significantly higher median levels of white blood cell (WBC) count, neutrophil-to-lymphocyte count ratio (NLR), high-sensitivity C-reactive protein (hsCRP), ferritin, interleukin 6 (IL-6), D-dimer, fibrinogen, and procalcitonin (PCT) compared to survivors at three different time points during hospitalization. In a multivariate analysis performed by a logistic regression model, serum 25(OH)D levels were significantly inversely associated with risk of COVID-19-related in-hospital mortality (odds ratio, 0.91; 95% confidence interval, 0.85-0.98; p = 0.01). According to receiver operating characteristic curve analysis, hsCRP, NLR, ferritin, and D-dimer were the best predictive biomarkers for poor prognosis of COVID-19, whereas IL-6, PCT, fibrinogen, 25(OH)D, WBC count, and tumor necrosis factor alpha (TNF-α) may serve as supportive biomarkers for worse clinical course of the disease. CONCLUSIONS: We found a markedly high prevalence (100%) of hypovitaminosis D in patients admitted to hospital with COVID-19, suggesting a possible role of low vitamin D status in increasing the risk of SARS-CoV-2 infection and subsequent hospitalization. The inverse association between serum 25(OH)D levels and risk of in-hospital mortality observed in our cohort suggests that a lower vitamin D status upon admission may represent a modifiable and independent risk factor for poor prognosis in COVID-19.

Bridging the Generational Digital Divide in the Healthcare Environment.

Increasing technological advances have generated a digital dependency in the population, resulting in a group of digitally excluded vulnerable people that lack basic digital skills. The aim of this study was to assess the digital divide in patients in relation to the healthcare environment. We explored the extent and effects of the digital health divide by undertaking a systematic review of the academic literature and comparing our findings with the results of a cross-sectional in-person survey answered by 881 people at four community pharmacies. In terms of the sociodemographic profile of the patients, we collected data regarding their gender, age, education level, and location (periphery or urban). The parameters evaluated were use of the internet to search for health information, use of telemedicine, use of different medical/healthcare applications, understanding explanations given by physicians regarding health, and asking pharmacists for help about newly prescribed treatments. Moreover, 168 pharmacists answered an online survey about how often they helped patients to make health center appointments or to download their COVID-19 vaccination certificate. Gender did not influence these results, but age, education level, and population location did. Those with the lowest levels of education required more help to request a health center appointment. People with high education levels and those living in an urban environment more often searched the internet for information about treatments that were new to them. Finally, people living in periphery areas received more help from their pharmacists, 60% of which said they had helped patients to download their COVID-19 vaccination certificate, with 24% of them saying they helped patients with this on a daily basis.

Evaluation of Natural and Vaccine-Induced Anti-SARS-CoV-2 Immunity: A Comparative Study between Different Groups of Volunteers.

(1) Background: The production of anti-SARS-CoV-2 antibodies should help minimize the severity of COVID-19 disease. Our focus was to investigate and compare different vaccination schedules, monitoring circulating S-RBD Ab (antibodies anti-Spike protein-Receptor Binding Domain) levels after administering two doses in naïve patients. Likewise, vaccine-stimulated immunity in naïve and previously infected patients was compared. (2) Methods: We included 392 patients. Sera were evaluated by Elecsys anti-SARS-CoV-2 S. Statistical analyses were conducted by MedCalc and JASP. (3) Results: In COVID-19 patients, the median value of Ab levels was 154 BAU/mL, stable up to 9 months after the infection. From the data observed in vaccinated patients, higher median values were recorded in COVID-19/Pfizer BioNTech (18913 BAU/mL) than in other groups (Pfizer BioNTech: 1841; ChadOx1 961; heterologous vaccination: 2687) BAU/mL. (4) Conclusions: In conclusion, a single booster dose given to previously infected patients raised an antibody response much higher than two doses given to naïve individuals and heterologous vaccination generated a robust persistent antibody response at high levels, steady up to three months after administration.

Leukocyte Telomere Length Variability as a Potential Biomarker in Patients with PolyQ Diseases.

SCA1, SCA2, and SCA3 are the most common forms of SCAs among the polyglutamine disorders, which include Huntington's Disease (HD). We investigated the relationship between leukocyte telomere length (LTL) and the phenotype of SCA1, SCA2, and SCA3, comparing them with HD. The results showed that LTL was significantly reduced in SCA1 and SCA3 patients, while LTL was significantly longer in SCA2 patients. A significant negative relationship between LTL and age was observed in SCA1 but not in SCA2 subjects. LTL of SCA3 patients depend on both patient's age and disease duration. The number of CAG repeats did not affect LTL in the three SCAs. Since LTL is considered an indirect marker of an inflammatory response and oxidative damage, our data suggest that in SCA1 inflammation is present already at an early stage of disease similar to in HD, while in SCA3 inflammation and impaired antioxidative processes are associated with disease progression. Interestingly, in SCA2, contrary to SCA1 and SCA3, the length of leukocyte telomeres does not reduce with age. We have observed that SCAs and HD show a differing behavior in LTL for each subtype, which could constitute relevant biomarkers if confirmed in larger cohorts and longitudinal studies.

Development, characterization, and ex vivo evaluation of an insert for the ocular administration of progesterone.

Progesterone (PG) affords neuroprotection in degenerative diseases associated to oxidative stress, such as cataracts, age-related macular degeneration, glaucoma, diabetic retinopathy and retinitis pigmentosa. The aim of this project was to develop ocular inserts for delivery of PG to the eye. Different inserts with PG in its composition were formulated and the insert with the best characteristics (59% polyvinyl alcohol, 39% polyvinylpyrrolidone K30 and 2% propylene glycol) was selected for ex vivo studies. Physical characteristics and drug release patterns of the insert were analysed. In vitro diffusion studies revealed a controlled diffusion of progesterone. Ex vivo experiments demonstrated similar trans-corneal and trans-scleral PG diffusion (corneal apparent permeability coefficient 6.46 ± 0.38 × 10-7 cm/s and scleral apparent permeability coefficient 5.87 ± 1.18 × 10-7 cm/s; mean ± SD; n = 5). However, the amount of PG accumulated in scleras was statistically higher than in corneas (30.07 ± 9.09 µg/cm2 and 15.56 ± 4.36 µg/cm2 respectively). The PG-loaded inserts (55.6 µg/cm2) were thin, translucent, showed no irritancy (HET-CAM test) and were elastic and robust, all suitable properties for its potential use in the treatment of several ocular diseases.

HPLC-UV analytical validation of a method for quantification of progesterone in ex vivo trans-corneal and trans-scleral diffusion studies.

Progesterone (PG) diminishes free radical damage and thus can afford protection against oxidative stress affecting the retina. The therapeutic use of PG is limited because it is a highly hydrophobic steroid hormone with very low solubility in water. This is the main drawback for the therapeutic application of PG at ocular level. The aims of this study were: (i) to analyze if PG causes ocular irritation (ii) to validate a HPLC method to determine PG in ex vivo studies and (iii) to evaluate PG permeation through cornea and sclera. A high performance liquid chromatographic method was developed and validated to detect PG incorporated to ß-cyclodextrin using a Waters Sunfire C18 (150 × 4.6 mm) reverse-phase column packed with 5 µm silica particles using a mobile phase consisted of a mixture of acetonitrile (ACN) and pure water 80:20 (v/v), pH 7.4. The limit of detection and the limit of quantification for 50 µL injection of PG were found to be 0.42 and 1.26 µg/mL, respectively. The calibration curve showed excellent linearity over the concentration range (0.5 µg/mL to 100 µg/mL). As proof of concept, ex-vivo experiments to investigate PG permeation through cornea and sclera with vertical diffusion cells were carried out to quantify PG diffusion. Ex vivo experiments demonstrate its applicability to investigate permeation levels of PG from 6.57 ±â€¯0.37 µg/cm2 at cornea and 8.13 ±â€¯0.85 µg/cm2 sclera. In addition, at the end of diffusion studies the amount of PG retained in each tissue was also quantified, and it was 40.87 ±â€¯9.84 µg/cm2 (mean ±â€¯SD; n = 6) in cornea and 56.11 ±â€¯16.67 µg/cm2 (mean ±â€¯SD; n = 6) in sclera.

The Influence of Vitamin D on Neurodegeneration and Neurological Disorders: A Rationale for its Physio-pathological Actions.

Vitamin D is a steroid hormone implicated in the regulation of neuronal integrity and many brain functions. Its influence, as a nutrient and a hormone, on the physiopathology of the most common neurodegenerative diseases is continuously emphasized by new studies. This review addresses what is currently known about the action of vitamin D on the nervous system and neurodegenerative diseases such as Multiple Sclerosis, Alzheimer's disease, Parkinson's disease and Amyotrophic Lateral Sclerosis. Further vitamin D research is necessary to understand how the action of this "neuroactive" steroid can help to optimize the prevention and treatment of several neurological diseases.

Ex-Vivo Trans-Corneal and Trans-Scleral Diffusion Studies with Ocular Formulations of Glutathione as an Antioxidant Treatment for Ocular Diseases.

Exposure to sunlight and contact with atmospheric oxygen makes the eye particularly susceptible to oxidative stress, which can potentially produce cellular damage. In physiological conditions, there are several antioxidant defense mechanisms within the eye. Glutathione (GSH) is the most important antioxidant in the eye; GSH deficit has been linked to several ocular pathologies. The aim of this study was to explore the potential for newly developed formulations allowing controlled delivery of antioxidants such as GSH and vitamin C (Vit C) directly to the eye. We have investigated the stability of antioxidants in aqueous solution and assessed ex-vivo the diffusion of GSH through two ocular membranes, namely cornea and sclera, either in solution or included in a semisolid insert. We have also carried out the hen's egg-chlorioallantoic membrane test (HET-CAM) to evaluate the ocular irritancy of the different antioxidant solutions. Our results showed that GSH is stable for up to 30 days at 4 °C in darkness and it is not an irritant to the eye. The diffusion studies revealed that the manufactured formulation, a semisolid insert containing GSH, could deliver this tripeptide directly to the eye in a sustained manner.

Multiple Sclerosis: kFLC index values related to gender.

BACKGROUND: Multiple sclerosis (MS) is a chronic multifactorial inflammatory and neurodegenerative disease of the central nervous system (CNS). The identification of biomarkers with good diagnostic and prognostic power is of great importance for monitoring and treating MS patients. METHODS: We analyzed serum and cerebrospinal fluid of 228 patients, with different neurological disorders and with MS to confirm our previous results and determine a possible gender difference of kFLC Index cut-off. RESULTS: We have obtained a kFLC Index cut-off of 12.5 (100% specificity and 90.4% sensitivity) and 11 (100% specificity and 97.5% sensitivity) for women and men with MS respectively. CONCLUSIONS: This study reinforces the importance that kFLC Index could have as a diagnostic aid to detect MS. Our data highlight a difference in the cut-off of the kFLC Index calculated by gender; male patients with a kFLC Index value greater than 11 are at higher risk to develop MS respect females having the same result.

Vitamin D Improves Neurogenesis and Cognition in a Mouse Model of Alzheimer's Disease.

The impairment of hippocampal neurogenesis at the early stages of Alzheimer's disease (AD) is believed to support early cognitive decline. Converging studies sustain the idea that vitamin D might be linked to the pathophysiology of AD and to hippocampal neurogenesis. Nothing being known about the effects of vitamin D on hippocampal neurogenesis in AD, we assessed them in a mouse model of AD. In a previous study, we observed that dietary vitamin D supplementation in female AD-like mice reduced cognitive decline only when delivered during the symptomatic phase. With these data in hand, we wondered whether the consequences of vitamin D administration on hippocampal neurogenesis are stage-dependent. Male wild-type and transgenic AD-like mice (5XFAD model) were fed with a diet containing either no vitamin D (0VD) or a normal dose of vitamin D (NVD) or a high dose of vitamin D (HVD), from month 1 to month 6 (preventive arm) or from month 4 to month 9 (curative arm). Working memory was assessed using the Y-maze, while amyloid burden, astrocytosis, and neurogenesis were quantified using immunohistochemistry. In parallel, the effects of vitamin D on proliferation and differentiation were assayed on primary cultures of murine neural progenitor cells. Improved working memory and neurogenesis were observed when high vitamin D supplementation was administered during the early phases of the disease, while a normal dose of vitamin D increased neurogenesis during the late phases. Conversely, an early hypovitaminosis D increased the number of amyloid plaques in AD mice while a late hypovitaminosis D impaired neurogenesis in AD and WT mice. The observed in vivo vitamin D-associated increased neurogenesis was partially substantiated by an augmented in vitro proliferation but not an increased differentiation of neural progenitors into neurons. Finally, a sexual dimorphism was observed. Vitamin D supplementation improved the working memory of males and females, when delivered during the pre-symptomatic and symptomatic phases, respectively. Our study establishes that (i) neurogenesis is improved by vitamin D in a male mouse model of AD, in a time-dependent manner, and (ii) cognition is enhanced in a gender-associated way. Additional pre-clinical studies are required to further understand the gender- and time-specific mechanisms of action of vitamin D in AD. This may lead to an adaptation of vitamin D supplementation in relation to patient's gender and age as well as to the stage of the disease.

Influence of Chemical Enhancers and Iontophoresis on the In Vitro Transdermal Permeation of Propranolol: Evaluation by Dermatopharmacokinetics.

The aims of this study were to assess, in vitro, the possibility of administering propranolol transdermally and to evaluate the usefulness of the dermatopharmacokinetic (DPK) method in assessing the transport of drugs through stratum corneum, using propranolol as a model compound. Four chemical enhancers (decenoic and oleic acid, laurocapram, and R-(+)-limonene) and iontophoresis at two current densities, 0.25 and 0.5 mA/cm² were tested. R-(+)-limonene, and iontophoresis at 0.5 mA/cm² were proven to be the most efficient in increasing propranolol transdermal flux, both doubled the original propranolol transdermal flux. Iontophoresis was demonstrated to be superior than the chemical enhancer because it allowed faster delivery of the drug. The DPK method was sufficiently sensitive to detect subtle vehicle-induced effects on the skin permeation of propranolol. The shorter duration of these experiments and their ability to provide mechanistic information about partition between vehicle and skin and diffusivity through skin place them as practical and potentially insightful approach to quantify and, ultimately, optimize topical bioavailability.

Ex vivo rabbit cornea diffusion studies with a soluble insert of moxifloxacin.

The objective of this research was to develop and evaluate an ocular insert for the controlled drug delivery of moxifloxacin which could perhaps be used in the treatment of corneal keratitis or even bacterial endophthalmitis. We have evaluated the ex vivo ocular diffusion of moxifloxacin through rabbit cornea, both fresh and preserved under different conditions. Histological studies were also carried out. Subsequently, drug matrix inserts were prepared using bioadhesive polymers. The inserts were evaluated for their physicochemical parameters. Ophthalmic ex vivo permeation of moxifloxacin was carried out with the most promising insert. The formulate insert was thin and provided higher ocular diffusion than commercial formulations. Ocular diffusion studies revealed significant differences between fresh and frozen corneas. Histological examinations also showed differences in the thickness of stroma between fresh and frozen corneas. The ophthalmic insert we have developed allows a larger quantity of moxifloxacin to permeate through the cornea than existing commercial formulations of the drug. Ocular delivery of moxifloxacin with this insert could be a new approach for the treatment of eye diseases.

Vitamin D, Cognition and Alzheimer's Disease: The Therapeutic Benefit is in the D-Tails.

Since its discovery during the epidemic of rickets in the early 1920s, the physiological effects of vitamin D on calcium/phosphorus homeostasis have been thoroughly studied. Along with the understanding of its actions on skeletal diseases and advances in cellular and molecular biology, this misnamed vitamin has gained attention as a potential player in a growing number of physiological processes and a variety of diseases. During the last 25 years, vitamin D has emerged as a serious candidate in nervous system development and function and a therapeutic tool in a number of neurological pathologies. More recently, experimental and pre-clinical data suggest a link between vitamin D status and cognitive function. Human studies strongly support a correlation between low levels of circulating 25-hydroxyvitamin D (25(OH)D) and cognitive impairment or dementia in aging populations. In parallel, animal studies show that supplementation with vitamin D is protective against biological processes associated with Alzheimer's disease (AD) and enhances learning and memory performance in various animal models of aging and AD. These experimental observations support multiple mechanisms by which vitamin D can act against neurodegenerative processes. However, clinical interventional studies are disappointing and fail to associate increased 25(OH)D levels with improved cognitive outcomes. This review collects the current available data from both animal and human studies and discusses the considerations that future studies examining the effects of vitamin D status on neurocognitive function might consider.

[Role of vitamin D in the physiopathology of neurodegenerative diseases]. / Rôle de la vitamine D dans la physiopathologie des maladies neurodégénératives.

The involvement of vitamin D in brain function has been discovered in the past 25 years by epidemiological and fundamental studies. Research on neurodegenerative diseases and their animal or cellular models unveiled converging lines of evidence indicating that hypovitaminosis D is not just an effect of the progression of neurodegenerative diseases, but truly an aggravating co-factor, sometimes very closely related to their physiopathology. Vitamin D is a steroid hormone capable of regulating the expression of hundreds of genes through both genetic and epigenetic mechanisms. This reflects the highly pleiotropic nature of its action in its conventional bone and phosphocalcic metabolism targets. Its role in the central nervous system and neurodegenerative diseases makes no exception to this rule. Here we focus on the identified role and mechanisms of vitamin D in multiple sclerosis, Alzheimer's disease and Parkinson's disease. The important prevalence of hypovitaminosis D under our latitudes in general and in at-risk groups in particular, its easy evaluation and correction, and the results of early clinical studies, suggest that vitamin D supplementation could usefully complement our therapeutic armory to fight these diseases.

Bioinformatics analysis of the serine and glycine pathway in cancer cells.

Serine and glycine are amino acids that provide the essential precursors for the synthesis of proteins, nucleic acids and lipids. Employing 3 subsequent enzymes, phosphoglycerate dehydrogenase (PHGDH), phosphoserine phosphatase (PSPH), phosphoserine aminotransferase 1 (PSAT1), 3-phosphoglycerate from glycolysis can be converted in serine, which in turn can by converted in glycine by serine methyl transferase (SHMT). Besides proving precursors for macromolecules, serine/glycine biosynthesis is also required for the maintenance of cellular redox state. Therefore, this metabolic pathway has a pivotal role in proliferating cells, including cancer cells. In the last few years an emerging literature provides genetic and functional evidences that hyperactivation of serine/glycine biosynthetic pathway drives tumorigenesis. Here, we extend these observations performing a bioinformatics analysis using public cancer datasets. Our analysis highlighted the relevance of PHGDH and SHMT2 expression as prognostic factor for breast cancer, revealing a substantial ability of these enzymes to predict patient survival outcome. However analyzing patient datasets of lung cancer our analysis reveled that some other enzymes of the pathways, rather than PHGDH, might be associated to prognosis. Although these observations require further investigations they might suggest a selective requirement of some enzymes in specific cancer types, recommending more cautions in the development of novel translational opportunities and biomarker identification of human cancers.