Study finds that early (defined as 1-2 weeks after diagnosis) surgery after diagnosis of uterine cancer is associated with increased complications including death. This compared to lower postoperative death rates in delay out to 3-4 weeks.
Patients with higher tumor markers are likely to have higher tumor burden, higher oxidative stress and, therefore, are more likely to have lower post IVC plasma levels.
Our data also showed that cancer patients with metastasis tend to have lower post-IVC vitamin C levels than those without metastasis
Lower peak plasma concentrations are obtained in cancer patients than in healthy subjects. Cancer patients who are deficient in vitamin C prior to therapy tend to achieve lower plasma levels post infusion.
Patients with higher inflammation or tumor burdens, as measured by CRP levels or tumor antigen levels, tend to show lower peak plasma ascorbate levels after IVC.
Patients with metastatic tumors tend to achieve lower post infusion plasma ascorbate levels than those with localized tumors.
The inflammatory microenvironment of cancer cells leads to increasing oxidative stress, which apparently depletes vitamin C, resulting in lower plasma ascorbate concentrations in blood samples post IVC infusion. Another explanation for this finding may be that cancers are themselves more metabolically active in their uptake of vitamin C, causing subjects to absorb more of the vitamin, and as a results show lower plasma ascorbate concentrations in blood post IVC infusion.
Most of the prostate cancer patients studied, 75±19% (95% confidence), showed reductions in PSA levels during the course of their IVC therapy
Laboratory studies suggest that, at high concentrations, ascorbate does not interfere with chemotherapy or irradiation and may enhance efficacy in some situations
Cameron and Pauling observed fourfold survival times in terminal cancer patients treated with intravenous ascorbate infusions followed by oral supplementation
Meta-analyses of clinical studies involving cancer and vitamins also conclude that antioxidant supplementation does not interfere with the efficacy of chemotherapeutic regiments
patients with severely elevated CRP levels attain plasma ascorbate concentrations after IVC infusions that are only 65% of those attained for subjects with normal CRP levels
The finding of decreased plasma ascorbate levels in cancer patients may relate to the molecular structure of ascorbic acid; in particular, the similarity of its oxidized form, dihydroascorbic acid, to glucose
Since tumor have increased requirement for glucose [67], transport of dehydroascorbate into the cancer cells via glucose transport molecules and ascorbate through sodium-dependent transporter may be elevated
Increased accumulation of ascorbic acid in the tumor site was supported by measurements of the level of ascorbic acid in tumors in animal experiments
Regarding inflammation, 73±13% of subjects (95% confidence) showed a reduction in CRP levels during therapy. This was an even more dramatic 86±13% (95% confidence) in subjects who started therapy with CRP levels above 10 mg/L
IVC therapy appears to reduce CRP levels in cancer patients.
CRP concentrations directly correlate with disease activity in many cases and can contribute to disease progression through a range of pro-inflammatory properties.
Being an exquisitely sensitive marker of systemic inflammation and tissue damage, CRP is very useful in screening for organic disease and monitoring treatment responses
ncreases in CRP concentrations have been associated with poorer prognosis of survival in cancer patients, particularly with advance disease independent of tumor stage
patients with advanced malignancies may have lower level of ascorbic acid in tissue, creating a higher demand for the vitamin C
patients treated by IVC with follow-up several year showed that suppression of inflammation in cancer patients by high-dose IVC is feasible and potentially beneficial
Inflammation is a marker of high cancer risk, and poor treatment outcome
The subjects with highly elevated CRP concentrations have a three-fold elevation “all-cause” mortality risk and a twenty-eight fold increase in cancer mortality risk
cancer patients may need higher doses to achieve a given plasma concentration.
patients with lower vitamin C levels may see more distribution of intravenously administered ascorbate into tissues and thus attain less in plasma.
When treating patients with IVC, the first treatment likely serves to replenish depleted tissue stores, if those subjects were vitamin C deficient at the beginning of the treatment. Then, in subsequent treatments, with increasing doses, higher plasma concentrations can be attained. On-going treatments serve to progressively reduce oxidative stress in cancer patients.
large doses given intravenously may result in maximum plasma concentrations of roughly 30 mM, a level that has been shown to be sufficient for preferential cytotoxicity against cancer cells
oral intake of vitamin C exceeded 200 mg administered once daily, it was difficult to increase plasma and tissue concentrations above roughly 200 μM.
Great review on the use of IV vitamin C in cancer and to reduce inflammation. The article does a great job of discussing the mechanism of vitamin C therapy in cancer as well as the proposed reasons for low vitamin C in cancer patients. The study also highlights the obstacles to rise in vitamin C levels post IV vitamin C in cancer patients.
As per Max Motamedian, this is where all the extra bloating and water weight can be avoided in the process Also about proteins and fibers as the most helpful factors in any given weight loss regimen.
not well understood, but it is felt to be a combination of both heat-induced necrosis and of protein inactivation (e.g., repair enzymes) as opposed to DNA damage
alterations in tumor cytoskeletal and membrane structures, which disrupt cell motility and intracellular signal transduction
A common explanation for HT-enhancement of RT and CT involves inhibition of homologous recombination repair of double-strand DNA breaks, preventing cells from repairing sub-lethal damage
it does appear to inhibit rejoining of RT-induced DNA breaks more than is commonly observed after RT alone
HT damages cells and enhances RT and CT sensitivity as a function of both temperature and duration of treatment
as temperature or duration increase, the rate of cell killing also increases
At temperatures above 42 °C, tumor vasculature is damaged, resulting in decreased blood flow
Cancer cells are particularly vulnerable to heating; in vivo studies have shown that temperatures in the range of 40–44 °C cause more selective damage to tumor cells
cancerous blood vessels are chaotic, leaky, and inefficient
selective cytotoxic effect on tumor cells include inhibition of key cancer cell-signaling pathways such as AKT, inducing apoptosis, suppression of cancer stem cell proliferation, and others
increase in immunological attacks against tumors after HT, which were believed to be achieved through activation of HSPs and subsequent modulation of the innate and adaptive immune responses against tumor cells
HT does lead to activation of the immune system and HSP-induced cell death through modification of the tumor cell surface
These HSPs and tumor antigens are taken up by dendritic cells and macrophages and go on to induce specific anti-tumor immunity
In vivo studies demonstrate HT-enhancement of NK cell activity, and HT has been shown to increase neutrophilic granulocytes with anti-tumor activity
it has become increasingly clear that HT results in immune stimulation, through both direct heat-mediated cell killing as well as innate and adaptive immune system modulation
The term hyperthermia is used in this review to refer to heating within the clinically accepted range of 40–45 °C
temperatures above 42.5–43 °C the exposure time can be halved with each 1 °C increase while maintaining equivalent cell killing
gradual heating at 43 °C for 1 h worked through an apoptotic pathway
short-term HFO introduces DNA methylation changes on a genome-wide scale in human skeletal muscle
These changes were only partly reversed after 6–8 weeks
The induction of DNA methylation changes after 5 days of HFO supports the growing awareness of DNA methylation as a dynamic signal that is possibly relevant to short-term day-to-day metabolic adaptations, including acute exercise
Diverging DNA methylation levels between elderly, but not young, genetically identical twins indicate that environmental exposures throughout life may permanently influence DNA methylation, suggesting some preservation of de novo DNA methylation in adults
our finding of a slow reversibility rate indicates the demethylation process may be somewhat impeded compared with the induction of methylation changes by diet, which could have implications for the preservation or build-up of CpG methylation over time
A slow reversibility of DNA methylation induced by carcinogenic agents has likewise been observed due to ingestion of high-fat diets in rodents
the relationship between DNA methylation and gene expression is not always straightforward
Study finds variability of methylation and some genetic expression alteration with high fat diet. Restated, what you eat interacts with your DNA to alter genetic expression. This has implications on initiation of therapy as well as response to therapy.
MicroRNAs (miRNAs), a major family of small RNAs, are ∼23 nt-long single strands of RNA that bind to mRNA transcripts to inhibit their translation
A recent study by Zhang et al. reported that plant-derived miRNAs can be found in human serum.
The group demonstrates that the plant miRNA miR168 may be taken up through dietary intake to inhibit the expression of its target low-density lipoprotein receptor 1 in the liver21, providing the first evidence that miRNA in food may influence gene expression in mammalian organs.
A more recent finding by the same group shows that a plant miRNA from honeysuckle is able to inhibit Influenza A replication22, indicating that plant miRNAs may be useful for treating human diseases.
We found that plant miR159 could be detected in human sera and its levels were inversely correlated with BC incidence and progression.
We further identified TCF7 as a mammalian target for miR159 and showed the anti-proliferative function of miR159 in BC cells using in vitro and in vivo models, demonstrating for the first time that a plant miRNA is able to influence BC cell growth.
certain dietary miRNAs from plants and other species may serve as highly affordable and powerful means of treatment with minimal inconvenience to patients.
miR159 which (using a synthetic mimic) targets TCF7 to inhibit the proliferation of cells whose growth is dependent on TCF7 such as the BC cells MDA-MB-231
our study using a BC model clearly indicates the anti-tumor effect of orally administered synthetic miR159 in its naturally existing form with the plant-specific 2'-O-methylation, suggesting the feasibility of using synthetic forms of plant miRNAs as dietary supplements in the treatment of human cancers, including those outside of the GI track
Experimental animal studies have shown that Borrelia burgdorferi, the agent of Lyme borreliosis, consistently establishes persistent infections in a variety of immunocompetent hosts, including laboratory mice [1], white-footed mice (Peromyscus leucopus) [2], [3], [4], rats [5], hamsters [6], guinea pigs [7], gerbils [8], dogs [9], and nonhuman primates, including rhesus macaques (Macaca mulatta) [10] and baboons (Papio spp.
With the advent of PCR, and more recently real-time quantitative PCR (qPCR), which offers greater sensitivity and specificity, B. burgdorferi-specific DNA has been found to persist for months following antibiotic treatment in tissues of experimentally infected mice [14], [15], [16], [17], [18], [19], [20], dogs [9], [21] and macaques [22], as well as humans
In addition, intact spirochetes have been demonstrated by immunohistochemistry in connective tissue of culture-negative treated mice and within ticks that fed upon them [15], [17] as well as in tissues of and ticks that fed upon treated macaques
Results of this study demonstrated not only persistence, but also resurgence of non-cultivable B. burgdorferi in tissues of mice at up to 12 months following antibiotic treatment
mouse model using ceftriaxone treatment regimen found that non-cultivatable B. burgdorferia persisted 8+ months post treatment and there was an increase in B. burgdorferi DNA in multiple sites at 12 months.
The levels of LH in the ibuprofen group had increased by 23% after 14 d of administration
This increase was even more pronounced at 44 d, at 33%
We found an 18% decrease (P = 0.056) in the ibuprofen group compared with the placebo group after 14 d (Fig. 1A) and a 23% decrease (P = 0.02) after 44 d (Fig. 1C). Taken together, these in vivo data suggest that ibuprofen induced a state of compensated hypogonadism during the trial,
which occurred as early as 14 d and was maintained until the end of the trial at 44 d
We first investigated testosterone production after 24 and 48 h of ibuprofen
exposure to assess its effects on Leydig cell steroidogenesis. Inhibition of testosterone levels was significant and dose-dependent
(β = −0.405, P = 0.01 at 24 h and β = −0.664, P < 0.0001 at 48 h) (Fig. 2A) and was augmented over time
The AMH data show that the hypogonadism affected not only Leydig cells but also Sertoli cells and also occurred as early
as 14 d of administration
Sertoli cell activity showed that AMH levels decreased significantly with ibuprofen
administration, by 9% (P = 0.02) after 14 d (Fig. 1B) and by 7% (P = 0.05) after 44 d compared with the placebo group
Examination of the effect of ibuprofen exposure on both the ∆4 and ∆5 steroid pathways (Fig. 2B) showed that it generally inhibited all steroids from pregnenolone down to testosterone and 17β-estradiol; the production
of each steroid measured decreased at doses of 10−5–10−4 M. Under control conditions, production of androstenediol and dehydroepiandrosterone (DHEA) was below the limit of detection
except in one experiment with DHEA
Measuring the mRNA expression of genes involved in steroidogenesis in vitro showed that ibuprofen had a profound inhibitory
effect on the expression of these genes (Fig. 3 B–D), consistent with that seen above in our ex vivo organ model. Taken together, these data examining effects on the endocrine
cells confirm that ibuprofen-induced changes in the transcriptional machinery were the likely reason for the inhibition of
steroidogenesis.
Suppression of gene expression concerned the initial conversion of cholesterol to the final testosterone synthesis. Hence,
expression of genes involved in cholesterol transport to the Leydig cell mitochondria was impaired
A previous study reported
androsterone levels decreased by 63% among men receiving 400 mg of ibuprofen every 6 h for 4 wk
We next examined the gene expression involved in testicular steroidogenesis ex vivo and found that levels of expression of
every gene that we studied except CYP19A1 decreased after exposure for 48 h compared with controls
the changes in gene expression indicate that the transcriptional machinery behind the endocrine action
of Leydig cells was most likely impaired by ibuprofen exposure.
Together, these data show that ibuprofen also directly impairs Sertoli cell function ex vivo by inhibiting transcription
ibuprofen use in men led to (i) elevation of LH; (ii) a decreased testosterone/LH ratio and, to a lesser degree, a decreased inhibin B/FSH ratio; and (iii) a reduction in the levels of the Sertoli cell hormone AMH
The decrease in the free testosterone/LH ratio resulted primarily
from the increased LH levels, revealing that testicular responsiveness to gonadotropins likely declined during the ibuprofen
exposure. Our data from the ex vivo experiments support this notion, indicating that the observed elevation in LH resulted
from ibuprofen’s direct antiandrogenic action
AMH levels were consistently suppressed by ibuprofen both in vivo and ex vivo, indicating that this hormone is uncoupled from
gonadotropins in adult men. The ibuprofen suppression of AMH further demonstrated that the analgesic targeted not only the
Leydig cells but also the Sertoli cells, a feature encountered not only in the human adult testis but also in the fetal testis
a chemical compound, through its effects on the signaling
compounds, can result in changes in the testis at gene level, resulting in perturbations at higher physiological levels in
the adult human
The analgesics acetaminophen/paracetamol and ibuprofen have previously been shown to inhibit the postexercise
response in muscles by repressing transcription
Previous ex vivo studies on adult testis have indeed pointed to an antiandrogenicity, only on Leydig cells, of phthalates
(41), aspirin, indomethacin (42), and bisphenol A (BPA) and its analogs
ibuprofen’s effects were not restricted to Leydig and Sertoli cells, as data showed that the expression of genes
in peritubular cells was also affected
short-term
exposure
In the clinical setting, compromised Leydig cell function resulting in increased insensitivity to LH is defined as compensated
hypogonadism (4), an entity associated with all-cause mortality
compensated hypogonadic men present with an increased likelihood of reproductive, cognitive, and physical symptoms
an inverse relationship was recently reported between endurance exercise training and male sexual libido
AMH concentrations are lower in seminal plasma from patients with azoospermia than
from men with normal sperm levels
inhibin B is a key clinical marker of reproductive health (32). The function of AMH, also secreted by Sertoli cells, and its regulation through FSH remain unclear in men
the striking dual effect of ibuprofen observed here on both Leydig and Sertoli cells makes this NSAID the chemical
compound, of all the chemical classes considered, with the broadest endocrine-disturbing properties identified so far in men.
after administration of 600 mg of ibuprofen to healthy
volunteers
নাম না জানা অনেক ফুলই পথের ধারে ফোটে,
এইতো সময় এলো তাদের রাখতে পুজোর ঘটে ।
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The spinal fusion surgery cost amount to only a fraction of that of their counterparts in most Western countries. The spinal fusion surgery cost is usually 25-50% less than that of equivalent treatment in the West
we wanted to investigate if other molecular targets and pathways may be used by SARS-CoV-2. We investigated the possibility of the spike 1 S protein and its receptor-binding domain (RBD) to target the epidermal growth factor receptor (EGFR) and its downstream signaling pathway in vitro using the lung cancer cell line (A549 cells). Protein expression and phosphorylation were examined upon cell treatment with the recombinant full spike 1 S protein or RBD. We demonstrate for the first time the activation of EGFR by the Spike 1 protein associated with the phosphorylation of the canonical Extracellular signal-regulated kinase1/2 (ERK1/2) and AKT kinases and an increase in survivin expression controlling the survival pathway.
play a role during the initial chemotactic response of neutrophils shortly after infection
following vitamin C supplementation, a 20% increase in neutrophil chemotactic activity was observed
also contributes to the phagocytosis and killing of microbes by neutrophils
low levels of vitamin C occurring in high-stress situations
maturation, proliferation, and viability of T cells have all been shown to be upregulated by the presence of normal physiologic concentrations of vitamin C
Vitamin C has been shown to directly affect the number of Igs released from B cells
vitamin C among healthy young adult males showed a significant increase in serum levels of IgA, IgG, and IgM
effects of high-dose vitamin C on cytokine levels in cancer patients, finding decreased amounts of the cytokines Interleukin-1 alpha (IL-1 alpha), IL-2, IL-8, and tumor necrosis factor-alpha (TNF-alpha) after high-dose vitamin C infusion
when vitamin C was supplemented with vitamin E in healthy adults, it increased the production of cytokines IL-1 beta and TNF-alpha
vitamin C acts to modulate the levels of cytokines to prevent them from fluctuating in either direction
vitamin C also acts as an important antioxidant to the cells of the immune system.
human leukocytes, neutrophils, in particular, possess the ability to transport the oxidized form of vitamin C across its membrane to use as a defense mechanism against ROS produced during an immune response
Vitamin C also can recover other endogenous antioxidants in the body such as vitamin E and glutathione, returning them to their active state
vitamin C can decrease the activation of NF-kB
can reduce harmful nitrogen-based compounds such as N-nitrosamines and nitrosamides, both of which are carcinogenic
subjects taking oral vitamin C supplementation saw a 60% to 90% reduction in oxidative stress compared to a placebo control
subjects infused with vitamin C alone had a 516% increase in glutathione levels compared to subjects not provided the 500 mg daily supplementation
hydroxylating proline and lysine
mature and stabilize the tissue of a healing wound
healing
oral surgery
improved soft tissue regeneration
vitamin C increases the mRNA levels of type I and type III collagen in the human dermis
Studies have demonstrated that those with low levels of vitamin C are at a significantly higher risk of respiratory infection compared to those with normal levels
viral cold duration was reduced by about 8% in adults and 13.5% in children using prophylactic daily doses of 200 mg of oral vitamin C
prophylactically supplementing vitamin C decreases the risk of infection with respiratory viruses such as the common cold
combined with probiotics, oral vitamin C supplementation showed a 33% decrease in the incidence of respiratory tract infections in preschool-age children [
high-dose oral supplementation of vitamin C managed to prevent or reduce symptoms if taken before or just after the onset of cold- or flu-like symptoms
improvements in oxygen saturation and decreased IL-6 levels (a marker of inflammation) in the treatment group compared to the control group
8 g doses of oral vitamin C
there is a negative correlation between age and serum levels of vitamin C
Patients with COVID-19 will likely also experience depletion in serum levels of vitamin C as a direct result of the upregulation of the immune system to combat the infection
Colunga et al. suggested that oral vitamin C can be combined with oral Quercetin, an antiviral flavonoid, to improve Quercetin’s ability to block viral membrane fusion of SARS-CoV-2
high doses of 1-2 g/day of oral vitamin C could prevent other upper respiratory infections
It appears vitamin C supplementation by itself does not provide a striking benefit in preventing COVID-19 infection for those without a deficiency
Flawed statement. What is normal? Vitamin D.
Many variables effect levels and dose, including the two compartment kinetics and absorption.
Hiedra et al. were able to show decreases in inflammatory biomarkers, such as D-dimer and ferritin
some evidence to support that prophylactic use of vitamin C helps reduce the severity of respiratory infection symptoms once a subject has already been infected
oral vitamin C in combination with zinc provided the largest amount of antibody titers 42 days
linear relationship between days of vitamin C therapy and survival duration
other studies were unable to find any definitive improvement concerning therapy with vitamin C
Either these studies are designed to fail or the authors are lacking some basic understanding of pharmacokinetics and pharmacodynamics with vitamin C.
Fowler et al. aimed to see if a high-dose vitamin C infusion would benefit patients affected by ARDS, but they were unable to conclude that vitamin C infusion, compared to a placebo, could decrease vascular inflammation and damage in ARDS
They are kind of make the point from my earlier note.
continuous vitamin C infusion at a rate of 60 mg/kg/day for four days decreased the need for mechanical ventilation and vasopressor use but had no significant effect on overall mortality
Again, designed to fail or ignorance designed the study which failed
Carr et al. suggested that high-dose IV vitamin C is most effective when treating sepsis as septic patients receiving the normal daily recommendations through diet still showed decreased vitamin C levels
High-dose IV vitamin C treatment has also been shown by Kakodkar et al. to decrease syndecan-1, an endothelial glycocalyx that contributes to mortality in septic patients
combined with hydrocortisone and thiamine, septic patients treated with 1.5 g of IV vitamin C every six hours showed a distinct decrease in their SOFA scores and none of the patients treated developed organ failure
combined with hydrocortisone and thiamine, septic patients treated with 1.5 g of IV vitamin C every six hours showed a distinct decrease in their SOFA scores and none of the patients treated developed organ failure
reduced overall mortality
reduced overall mortality
propose the use for high-dose vitamin C to aid in the treatment of septic shock-induced hypotension
treatment of severe sepsis using a high dose (up to 200 mg/kg/day) of IV vitamin C was explored in phase I, a double-blind, randomized, placebo-controlled trial by Fowler et al. [75]. Their findings included a reduction in SOFA scores and decreased vascular injury compared to a placebo control group, all while showing minimal adverse side effects