-
Nutrients Nov 2023Several risk factors, including nutritional/lifestyle ones, play a role in gastric cancer etiology. Further interactions with mental health have also been emphasized. We...
Several risk factors, including nutritional/lifestyle ones, play a role in gastric cancer etiology. Further interactions with mental health have also been emphasized. We hypothesized that individuals with mental disorders would exhibit compromised nutrient intake, increasing their risk of gastric cancer. The state of mental health was evaluated in 82 patients with gastric cancer and 95 healthy controls using the 21-item Depression-Anxiety-Stress Scale. The participants' dietary intakes were evaluated by a 168-item food frequency questionnaire. Based on fully adjusted logistic regressions, there was a significant association between depression (OR = 1.938, CI 95%: 1.009-3.723) and stress (OR = 2.630, CI 95%: 1.014-6.819) with increased odds of gastric cancer. According to fully adjusted multinomial regressions, vitamins A and B6, beta-carotene, and black tea decreased the odds of depression, based on comparing the control group with cases of depression, while sugar and salt increased its odds. The highest significant association was found for salt intake and anxiety in cases with present anxiety (OR = 4.899, 95% CI: 2.218-10.819), and the highest significant protective effect was found for vitamin B6 and depression in cases with present depression (OR = 0.132, 95% CI: 0.055-0.320). However, considering causal relationships and clarifying the underlying mechanisms is imperative and requires further investigation. Advising healthy dietary patterns, e.g., a Mediterranean diet rich in vitamins, minerals, and phytochemicals such as vitamin A, B6, beta-carotene, and fiber, is expected to reduce the odds of gastric cancer, possibly related to lower levels of anxiety and depression.
Topics: Humans; beta Carotene; Depression; Stomach Neoplasms; Case-Control Studies; Mental Health; Diet; Vitamins; Vitamin A; Mental Disorders
PubMed: 38068839
DOI: 10.3390/nu15234981 -
Cureus Nov 2023Pyridoxal kinase (PDXK) plays a pivotal role as an essential enzyme in cellular processes. It catalyzes the phosphorylation of pyridoxal, pyridoxamine, and pyridoxine to...
Pyridoxal kinase (PDXK) plays a pivotal role as an essential enzyme in cellular processes. It catalyzes the phosphorylation of pyridoxal, pyridoxamine, and pyridoxine to generate pyridoxal 5'-phosphate (PLP), the bioactive form of vitamin B6. An intriguing link has emerged between elevated expression levels of PDXK and PLP and various types of carcinomas, including leukemia. Leukemic cells have an increased need for vitamin B6 to sustain their survival and rapid growth, highlighting the potential of targeting PDXK-PLP as a promising therapeutic target in cancer treatment. To discover a novel and promising PDXK inhibitor, we conducted a comprehensive screening of compounds derived from both natural sources and drug-like databases. Our approach involved employing structure-based virtual screening and molecular docking techniques to attenuate the phosphorylation of PLP. Among the top six compounds, ZINC095099376 (referred to as C03) emerged as the most potent inhibitor of PDXK, primarily due to its exceptional binding affinity and remarkable specificity for the target protein. Furthermore, our investigation revealed that compound C03 establishes crucial interactions with key residues within the substrate binding site, indicating that it binds at the same site as the co-crystallized ligand. Remarkably, compound C03 inhibited the endogenous PDXK expression, showed anti-proliferative activity, and triggered an intrinsic pathway for apoptosis via the activation of key apoptotic factors in leukemic cells. In summary, these findings strongly indicate that compound C03 holds promise as a novel inhibitor of PDXK, offering the potential for the development of effective treatments for leukemia.
PubMed: 38046746
DOI: 10.7759/cureus.48176 -
Cureus Oct 2023Pyridoxine deficiency is a prevalent condition in the United States that primarily affects patients with alcohol use disorder. The presentation of this condition is very...
Pyridoxine deficiency is a prevalent condition in the United States that primarily affects patients with alcohol use disorder. The presentation of this condition is very nonspecific and commonly presents with a constellation of symptoms including peripheral neuropathy, stomatitis, dermatitis, confusion, depression, encephalopathy, and seizures. Over half of these patients have associated alcohol use disorder, which causes pyridoxine deficiency due to the breakdown of pyridoxal phosphate during ethanol metabolism in the liver. As an important cofactor in the synthesis of γ-aminobutyric acid (GABA), deficient levels of pyridoxine may lower the seizure threshold due to reduced GABA-mediated inhibition. This case details a 57-year-old male with chronic alcoholism and a history of seizures who developed episodes of myoclonic jerks, tremors, anxiety, and neuropathy whose symptoms persisted even while on anti-epileptic medication. He was found to have pyridoxine deficiency and had full resolution of symptoms shortly after the administration of vitamin B6 supplementation. Pyridoxine deficiency may lead to severe neurologic disorders such as encephalopathy and seizures. Hence, it is important to consider pyridoxine deficiency in the workup of neurologic complaints, especially in high-risk patients.
PubMed: 38021490
DOI: 10.7759/cureus.47647 -
Current Therapeutic Research, Clinical... 2023Motion sickness (kinetosis) is a common and temporarily incapacitant ailment, manageable with behavioral as well as pharmacological measures.
A Combination of Gamma-Aminobutyric Acid, Glutamic Acid, Calcium, Thiamine, Pyridoxine, and Cyanocobalamin vs Ginger Extract in the Management of Chronic Motion Sickness: A Clinical Evaluation.
BACKGROUND
Motion sickness (kinetosis) is a common and temporarily incapacitant ailment, manageable with behavioral as well as pharmacological measures.
OBJECTIVE
To assess the effectiveness and safety of a combination of gamma-aminobutyric acid, glutamic acid, calcium, thiamine, pyridoxine, and cyanocobalamin (Group A) (n = 170) and extract of (ginger) (Group B) (n = 165) in the management of chronic complaints consistent with motion sickness.
METHODS
Both groups were tested according to the following end points, under self-paired as well as comparative study designs: reduction of ≥20 score points in the total motion sickness assessment questionnaire (MSAQ) score, percentage of patients presenting a reduction of the total MSAQ score, absolute MSAQ score reduction, physician's assessment scores, final overall assessment of study medication, and willingness to continue treatment. Safety was also evaluated.
RESULTS
There was a statistically significant better performance under both study designs for Group A ( = 0.05 using different statistical tests) in all end points. Both regimens were safe, with different neurological and gastrointestinal tolerability outcomes.
CONCLUSIONS
Group A and Group B regimens were effective and safe in the management of chronic complaints consistent with motion sickness and the Group A regimen was more effective than Group B.
PubMed: 38021267
DOI: 10.1016/j.curtheres.2023.100719 -
Drug Metabolism and Disposition: the... Nov 2023Our recent study revealed that SLC49A4, known as disrupted in renal carcinoma 2, is a H-coupled lysosomal exporter for pyridoxine (vitamin B6), a cationic compound, and...
Our recent study revealed that SLC49A4, known as disrupted in renal carcinoma 2, is a H-coupled lysosomal exporter for pyridoxine (vitamin B6), a cationic compound, and involved in the regulation of its lysosomal and cellular levels. We here examined a possibility that this transporter might also transport cationic amphiphilic drugs (CADs) that are known to undergo lysosomal trapping, using pyrilamine, an H-antagonist, as a model CAD and the COS-7 cell line as a model cell system for transient introduction of human SLC49A4 and a recombinant SLC49A4 protein (SLC49A4-AA), in which the N-terminal dileucine motif involved in lysosomal localization was removed by replacing with dialanine for redirected localization to the plasma membrane. The introduction of SLC49A4 into COS-7 cells induced a significant decrease in the accumulation of pyrilamine in the intracellular compartments in the cells treated with digitonin for permeabilization of plasma membranes, suggesting its operation for lysosomal pyrilamine export. Accordingly, functional analysis using the SLC49A4-AA mutant, which operates for cellular uptake at the plasma membrane, in transiently transfected COS-7 cells demonstrated its H-coupled operation for pyrilamine transport, which was saturable with a Michaelis constant of 132 μM at pH 5.5. In addition, many CADs that may potentially undergo lysosomal trapping, which include imipramine, propranolol, verapamil, and some others, were found to inhibit SLC49A4-AA-mediated pyrilamine transport, suggesting their affinity for SLC49A4. These results suggest that SLC49A4 is involved in the lysosomal trapping of pyrilamine, operating for its exit. The CADs that inhibited SLC49A4-AA-mediated pyrilamine transport could also be SLC49A4 substrate candidates. SLC49A4 mediates the transport of pyrilamine in a H-coupled manner at the lysosomal membrane. This could be a newly identified mechanism for lysosomal export involved in its lysosomal trapping.
PubMed: 37963658
DOI: 10.1124/dmd.123.001354 -
Journal of Clinical Medicine Oct 2023Antioxidants reduce arterial stiffness, but the effects previously reported are weak. A systematic review of the antioxidants vitamin E, vitamin C, vitamin A, and...
Antioxidants reduce arterial stiffness, but the effects previously reported are weak. A systematic review of the antioxidants vitamin E, vitamin C, vitamin A, and beta-carotenes (the most commonly studied antioxidants) on pulse wave velocity (PWV) found an effect size of only -0.20 (approximately -16 m/s or -2.5%). Studies in rats of the potent pro-oxidant substance acetaldehyde have shown that combinations of sulfur-containing antioxidants, including thiamine and l-cysteine, with ascorbic acid potently protect against oxidative-stress-mediated mortality. The effects of these combinations of oxidants on PWV have not been studied. The present study evaluated the effects of 2 weeks of therapy with a combination of sulfur-containing antioxidants (cysteine, thiamine, and pyridoxine) in combination with ascorbic acid on stiffness index (SI), a measure of arterial stiffness that is strongly correlated with PWV, using a Pulse Trace recorder in a diverse group of 78 volunteers. SI fell by -1.7 m/s relative to placebo (95% confidence intervals -0.6 to -2.7 m/s), a reduction of -19% (95% confidence intervals -9% to -31%). The Glass effect size was 1.4, indicating a very strong treatment effect which was substantially greater than the effect size found in previous studies of antioxidants. PWV reduction was correlated significantly with increasing age. Further studies of similar antioxidant combinations are required to determine whether they are of value in the treatment or prevention of cardiovascular disease.
PubMed: 37959269
DOI: 10.3390/jcm12216804 -
Foods (Basel, Switzerland) Nov 2023Rice ( L.) is the principal staple food, a fundamental component of food security, a significant source of energy and major nutrients, and a key player in the overall...
Rice ( L.) is the principal staple food, a fundamental component of food security, a significant source of energy and major nutrients, and a key player in the overall nutritional status in Bangladesh. Parboiling is a common rice-processing treatment in Bangladesh. Recently, polishing has also become a common practice among millers seeking to attract consumers. Polishing may influence the nutrient composition of rice. The present study aimed to investigate the impact of parboiling and polishing on the nutritional content of the five High Yield Varieties (HYVs) of rice (BR11, BRRI dhan28, BRRI dhan29, BRRI dhan49, and BRRI dhan84) and their percent contributions to the Recommended Dietary Allowances (RDA) of vitamins and minerals. All of the rice samples were analyzed for proximate parameters, vitamins (B1, B2, B3, B6, and folate), and minerals (Ca, Mg, Fe, Zn, Na, K, P). Moisture, ash, fat, and total dietary fiber (TDF) were determined gravimetrically, according to the AOAC Official Methods; protein was measured by the Kjeldahl method; B-group vitamins were measured using Ultra Pressure Liquid Chromatography; and mineral content was determined by ICP-OES. The energy, protein, fat, and total dietary fiber (TDF) content of the samples ranged between 342-357 kcal/100 g, 6.79-10.74 g/100 g, 0.31-1.69 g/100 g, and 2.59-3.92 g/100 g respectively. Thiamin, riboflavin, niacin, pyridoxin, and folate content ranged from 0.11-0.25 mg/100 g, 0.01-0.05 mg/100 g, 2.82-6.42 mg/100 g, 0.12-0.30 g/100 g, and 5.40-23.95 g/100 g respectively. In a comparison of parboiling and polishing, macronutrients and vitamin retention were higher in parboiled unpolished rice than in polished unparboiled rice. The minerals (mg/100 g) Ca, Mg, Fe, Zn, Na, K, and P were in the ranges 32.82-44.72, 30.69-58.34, 0.51-0.70,1.83-2.79, 5.00-5.36, 106.49-112.73, and 162.23-298.03. Minerals of BRRI dhan84 were unaffected by polishing and parboiling. BRRI dhan84 contributed a higher percentage of RDA of all B vitamins and minerals. Therefore, to reduce nutrient loss in rice, industries and consumers should be encouraged to avoid polishing or limit polishing to 10% DOM and to consume unpolished rice, either parboiled or unparboiled.
PubMed: 37959116
DOI: 10.3390/foods12213997 -
Journal of Medical Case Reports Oct 2023Few reports have described multidisciplinary treatment, including extracorporeal shock wave therapy, for patients with refractory chronic tension-type headache. In this...
BACKGROUND
Few reports have described multidisciplinary treatment, including extracorporeal shock wave therapy, for patients with refractory chronic tension-type headache. In this study, we conducted multidisciplinary treatment for a patient with chronic tension-type headache who suffered from chronic headache refractory to treatment.
CASE PRESENTATION
The patient was a 45-year-old Japanese male suffering from 20 years of headache. As his headache had worsened recently, he visited a local clinic. With the diagnosis of suspected tension-type headache, its treatment was unsuccessful and he was referred to our hospital. The neurology department confirmed the tension-type headache and prescribed another medication, but he showed no improvement. Then, the patient was referred to the rehabilitation medicine department for consultation. At the initial visit, we identified multiple myofascial trigger points in his bilateral posterior neck and upper back regions. At the initial visit, he was prescribed 10 mL of 1% lidocaine injected into the muscles in these areas. In addition, he received 2000 extracorporeal shock wave therapy into bilateral trapezius muscles, and was instructed to take oral Kakkonto extract granules, benfotiamine, pyridoxine hydrochloride, and cyanocobalamin. Cervical muscle and shoulder girdle stretches and exercises were also recommended. At follow-up treatment visits, we used extracorporeal shock wave therapy to bilateral trapezius muscles, which led to immediate pain relief. After 11 weeks, he was not taking any medication and his headache was subjectively improved and his medical treatment ended.
CONCLUSION
A patient with chronic tension-type headache refractory to regular treatment was successfully treated with a multimodal approach including extracorporeal shock wave therapy in addition to standard treatment. For patients with tension-type headache accompanied by myofascial trigger points, it may be recommended to promptly consider aggressive multimodal treatment that includes extracorporeal shock wave therapy.
Topics: Humans; Male; Middle Aged; Combined Modality Therapy; Extracorporeal Shockwave Therapy; Headache; Myofascial Pain Syndromes; Tension-Type Headache
PubMed: 37907963
DOI: 10.1186/s13256-023-04092-9 -
Molecules (Basel, Switzerland) Oct 2023The classical least squares (CLS) model and three augmented CLS models are adopted and validated for the analysis of pyridoxine HCl (PYR), cyclizine HCl (CYC), and...
The classical least squares (CLS) model and three augmented CLS models are adopted and validated for the analysis of pyridoxine HCl (PYR), cyclizine HCl (CYC), and meclizine HCl (MEC) in a quinary mixture with two related impurities: the CYC main impurity, Benzhydrol (BEH), which has carcinogenic and hepatotoxic effects, and the MEC official impurity, 4-Chlorobenzophenone (BEP). The proposed augmented CLS models are orthogonal signal correction CLS (OSC-CLS), direct orthogonal signal correction CLS (DOSC-CLS), and net analyte processing CLS (NAP-CLS). These models were applied to quantify the three active constituents in their raw materials and their corresponding dosage forms using their UV spectra. To evaluate the CLS-based models sensibly, we design a comparative study involving two sets: the training set to construct models and the validation set to assess the prediction abilities of these models. A five-level, five-factor calibration design was established to produce 25 mixtures for the calibration set. In addition, 16 experiments were performed for a test set distributed equally between the in-space and out-space samples. The primary criterion for comparing the models' performance was the validation set's root mean square error of prediction (RMSEP) value. Finally, augmented CLS models showed acceptable results for assaying the three analytes. The results were compared statistically with the reported HPLC methods; however, the DOSC-CLS model proved the best for assaying the dosage forms.
Topics: Antiemetics; Least-Squares Analysis; Meclizine; Calibration; Chromatography, High Pressure Liquid
PubMed: 37894524
DOI: 10.3390/molecules28207044 -
Biosensors Sep 2023Adjusting the morphological characteristics of a material can result in improved electrocatalytic capabilities of the material itself. An example of this is the...
Adjusting the morphological characteristics of a material can result in improved electrocatalytic capabilities of the material itself. An example of this is the introduction of rare-earth elements into the borate structure, which gives a new perspective on the possibilities of this type of material in the field of (bio)sensing. In this paper, we present the preparation of borates including La, Nd and Dy and their application for the modification of a glassy carbon electrode, which is used for the non-enzymatic detection of a biologically relevant molecule, vitamin B6 (pyridoxine). Compared with the others, dysprosium borate has the best electrocatalytic performance, showing the highest current and the lowest impedance, respectively, as determined using cyclic voltammetry and impedance tests. Quantitative testing of B6 was performed in DPV mode in a Britton-Robinson buffer solution with a pH of 6 and an oxidation potential of about +0.8 V. The calibration graph for the evaluation of B6 has a linear range from 1 to 100 μM, with a correlation coefficient of 0.9985 and a detection limit of 0.051 μM. The DyBO-modified electrode can be used repeatedly, retaining more than 90% of the initial signal level after six cycles. The satisfactory selectivity offered a potential practical application of the chosen method for the monitoring of pyridoxine in artificially prepared biological fluids with acceptable recovery. In light of all the obtained results, this paper shows an important approach for the successful design of electrocatalysts with tuned architecture and opens new strategies for the development of materials for the needs of electrochemical (bio)sensing.
Topics: Pyridoxine; Borates; Carbon; Electrodes
PubMed: 37887094
DOI: 10.3390/bios13100901