•Diabetes mellitus and hyperglycemia significantly affect the incidence and prognosis of colorectal cancer.•Evidence of the effects of metformin remain controversial in cancer prognosis.•Potential ...molecular mechanisms by which DM and hyperglycemia affects cancer risk.•Potential roles of glucose modulation in CRC therapy.
Diabetes mellitus (DM) and hyperglycemia have been shown to have significant effects on the incidence, chemoresistance, and prognosis of colorectal cancer (CRC), as well as the outcomes of localized and metastatic CRC. Inflammation and endocrine effects may act as central mechanisms of DM and cancer and stimulate the insulin‐like growth factor 1–phosphoinositide 3-kinase–Akt–mammalian target of rapamycin (IGF-1–PI3K–AKT–mTOR) pathway. Dysregulation of the AMP-activated protein kinase (AMPK) pathway leads to metabolic imbalance and indicates cancer risk. The use of metformin for chemoprevention has been shown to reduce CRC and adenoma incidence through the upregulation of AMPK, which causes cell cycle arrest in the Gap 1–S (G1–S) phase and inhibits the mTOR pathway, even potentially reversing the epithelial–mesenchymal transition. However, evidence of the effects of metformin remain controversial in cancer prognosis. Several genes, such as transcription factor 7-like 2(TCF7L2), tumor protein P53 inducible nuclear protein 1(TP53INP1), gremlin 1 (GREM1), and potassium voltage-gated channel subfamily Q member 1(KCNQ1), are pleiotropically related to DM as well as cancer risk and prognosis. Epigenetic modification of members of the Let-7 family such as miR-497, miR-486, and miR-223 is strongly associated with impaired glucose tolerance and CRC risk. Herein we review the pathophysiological and epidemiological evidence as well as potential underlying molecular mechanisms by which DM and hyperglycemia affect CRC risk. We also suggest potential roles of glucose modulation in CRC therapy and propose an agenda for future research and clinical practice.
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Background:
The high prevalence of type 2 diabetes mellitus (DM) among patients with colorectal cancer (CRC) is becoming a serious public health concern worldwide. FOLFOX4 chemotherapy is one of the ...most widely used adjuvant therapies in patients with stage III colon cancer after surgical resection. However, chemotherapy resistance is associated with a poor prognosis. The prognostic impact of high blood sugar levels on oxaliplatin resistance in CRC patients is an unexplored topic.
Methods:
In total, 157 patients with stage III CRC were classified according to their fasting blood sugar level (⩾126 or <126 mg/dl). Clinicopathological features and oxaliplatin chemoresistance/survival outcome of the two groups were compared. In vitro cell proliferation assay was performed through d-(+)-glucose administration.
Results:
Multivariate analysis results revealed that high blood sugar level was a significantly independent prognostic factor of disease-free survival and overall survival (both p < 0.05), but not DM history. After metformin administration, enhanced proliferation of CRC cells (HT-29, HCT-116, SW480, and SW620) with d-(+)-glucose administration could be reversed and oxaliplatin chemosensitivity considerably increased (p < 0.05). Furthermore, phosphorylation of two glycolysis-related target proteins, SMAD3 and MYC, notably increased under high glucose concentration.
Conclusions:
Hyperglycemia can affect clinical outcomes in stage III CRC patients receiving adjuvant chemotherapy, and the mechanism underlying oxaliplatin resistance is possibly associated with increased phosphorylation of SMAD3 and MYC and upregulation of EHMT2 expression.
In this study, the antimicrobial agents of mono(hydroxyethoxyethyl)phthalate (M(HEEP)
) with different metal of M = Zn, Mn, Pb, and Ca were synthesized from diethylene glycol (DEG), phthalic ...anhydride (PA), and divalent metal acetates including calcium acetate, zinc acetate, manganese acetate, and lead acetate, respectively. The waterborne urethane oil (WUO) dispersions synthesized from linseed oil, diisocyanates (hexamethylene diisocyanate (HDI) and isophorone diisocyanate (IPDI)), dimethylolpropionic acid at NCO/OH molars of 0.9, by acetone processing method were described as in our previous report. The M(HEEP)
antimicrobial agents as well as the commercial nanosilver powder were added into WUO dispersions as the antimicrobial coatings. The effects of various antimicrobial agents and dosages (0.0, 0.2, 0.6, 0.8, 1.0, 2.0, and 4.0 phr) on antimicrobial activity of WUO films against gram-negative bacterium of
, gram-positive bacterium of
, brown-rot fungus of
, and white-rot fungus of
were assessed. In addition, the film properties of the best antimicrobial WUO coatings were also examined. The results showed that the antimicrobial agents of mono(hydroxyethoxyethyl) phthalate M(HEEP)
(M = Zn, Mn, Pb, and Ca) powders should certainly be synthesized by FTIR,
H-NMR,
C-NMR, and energy-dispersive X-ray spectroscopy (EDS) identifications and the yields of them were 43-55%. The results also revealed that the WUO film synthesizing with HDI films containing Zn(HEEP)
of 2.0 phr and Pb(HEEP)
of 0.4 phr had the best antibacterial activity for
and
, respectively. The IPDI films containing Zn(HEEP)
of 1.0 phr had the best antibacterial activity for both
and
For antifungal activity, the WUO film synthesizing with HDI films containing Pb(HEEP)
of 0.8 phr and Zn(HEEP)
of 2.0 phr as well as IPDI films containing Mn(HEEP)
of 0.2 phr and Zn(HEEP)
of 4.0 phr had the best performances against
and
, respectively. Comparing with commercial nanoAg powder, the Zn(HEEP)
and Pb(HEEP)
had a superior antifungal efficiency for
and
, while it had a slightly inferior efficiency in the antibacterial activity for
and
. On the properties of WUO films, adding metal-containing antimicrobial agents could slightly enhance the thermal stability, but lowered the gloss of all films, however, the
value increased for HDI film and decreased for IPDI film. In addition to this, they had no significant difference in the film properties including hardness, impact resistance, bending resistance, adhesion, mass retention, and light-fastness between the WUO films with and without adding antimicrobial agents.
Patients with cancer use low-molecular-weight fucoidan (LMF) as a supplement to therapy. However, most studies of LMF are in vitro or conducted using animals. Concurrent chemoradiotherapy (CCRT) is ...the gold standard for locally advanced rectal cancer (LARC). This study investigated the quality of life (QoL) and clinical outcomes of patients with LARC taking LMF as a supplement to neoadjuvant CCRT. This was a double-blind, randomized, placebo-controlled study. The sample comprised 87 patients, of whom 44 were included in a fucoidan group and 43 were included in a placebo group. We compared their QoL scores and clinical outcomes before treatment, and at 1 month, 2 months, and 3 months posttreatment. Pretreatment and posttreatment gut microbiota differences were also compared. Although enhanced physical well-being (PWB) at 2 months and 3 months posttreatment in the fucoidan group were observed (both P < .0125), the improvements of the Functional Assessment of Cancer Therapy for Patients with Colorectal Cancer (FACT-C) were nonsignificant (all P > .0125). Skin rash and itching and fatigue were less common in the fucoidan group (both P < .05). Posttreatment, the genus Parabacteroides was significantly more common in the gut microbiota of the fucoidan group. LMF administration improved the QoL, skin rash and itching, fatigue, and gut microbiota composition of the patients with LARC receiving CCRT.
Clinical Trial Registration: NCT04342949
► We used castor oil to produce the polyol for 2-package waterborne PU wood coatings. ► The film containing IPDI hardener had excellent gloss and hardness. ► The film containing PEG-modified PIPDI ...hardener had the lowest hardness. ► The film containing PEG-modified PHDI hardener showed the best elongation at break. ► The coating containing HDI hardener is most suitable for wood finishing.
The effects of four kinds of hardener on the properties of castor oil (CO) based 2-package waterborne polyurethane (2K-WPU) wood coatings were examined. Modified castor oil (MCO) was prepared by transesterification of glycerol and CO at the molar ratio of 2.0. The waterborne polyurethane-dispersed polyol (PUDp), one component of the 2K-WPU, was synthesized from MCO, dimethylol propionic acid (DMPA) and isophorone diisocyanate (IPDI) by the acetone process to provide a prepolymer with a carboxyl and hydroxyl groups. Then the prepolymer was neutralized by triethylamine (TEA) and dispersed into water. After vacuum distillation to remove acetone, the PUDp was obtained and then mixed with four different hardeners: IPDI, hexamethylene diisocyanate (HDI), polyethylene glycol (PEG) modified PIPDI (polymeric IPDI) and PEG-modified PHDI (polymeric HDI). The NCO/OH molar ratio of 1.5 was used and a 2K-WPU coating was obtained. The results showed that the film of the 2K-WPU coatings obtained from IPDI hardener had excellent gloss and hardness. On the contrary, the film containing PEG-modified PIPDI hardener (PEG-PIPDI) had lower hardness and gloss but higher tensile strength. The film containing PEG-modified PHDI hardener (PEG-PHDI) showed the best elongation at break, abrasion resistance and impact resistance, though it had the worst hardness. The film with HDI hardener had the best hardness and highest tensile strength and superior water resistance among all the films with different hardeners, and it was suitable for wood coatings.
In our previous report, the antibacterial agents with different metals, mono(hydroxyethoxyethyl)phthalate M(HEEP)2, M = Zn, Mn, and Ca, were synthesized. For increasing their yields, modified ...synthesis and purified processes were further investigated. The result of energy-dispersive X-ray spectroscopy showed the M(HEEP)2 could be stable and successfully synthesized, and their yields were raised to 73–85% from our previous report of 43–55%. For ultraviolet-cured wood floor coating application, the Zn(HEEP)2 was selected as an antibacterial agent and mixed with commercial UV wood floor coating. The effects on the antibacterial activity of UV films with different Zn(HEEP)2 additions of 0, 4, 8, and 12 phr as well as the commercial nano-Ag of 12 phr against Escherichia coli were evaluated. In the static antibacterial test, the UV films with Zn(HEEP)2 additions had similar antibacterial activity of 57–59%. In another dynamic shaking antibacterial test, the film containing 12 phr Zn(HEEP)2 had the best antibacterial activity among all the UV films. On the film properties, the Zn(HEEP)2-containing UV films had lower gloss and abrasion resistance, and slightly increased the hardness than those of UV film without Zn(HEEP)2 addition. However, there were no noticeable differences in mass retention, lightfastness, and thermal stability between UV films with and without the Zn(HEEP)2 addition. In this study, the 12 phr Zn(HEEP)2-containing UV film provided the best antibacterial activity against E. coli and had the balanced film properties for application on the UV wood floor coating.
Oriental lacquer is a natural polymeric coating with a satiny texture and excellent characteristics, such as chemical resistance and durability. However, the poor lightfastness resulted in the ...natural aromatic structures of the urushiol structures limited its suitability for outdoor application. This study aimed at the improvement of the lightfastness by adding the different hindered amine light stafbilizers (HALS) with 2 phr addition as well as the effects on the coating and film property of the refined oriental lacquers (RL). The
plate, glass sheets, and the other substrates were used for finishing. The results showed that the lightfastness of RL film was obviously improved by adding 2 phr HALS of Bis(2,2,6,6-tetramethyl-4-piperidinyl) sebacate (H90) containing -NH group and Bis (1,2,2,6,6-pentamethyl-4-piperidinyl)-3,5-bis(1,1-dimethyl ethyl) -4-hydroxyphenyl methyl butylmalonate (H60) containing -NCH
groups. The HALS additions increased the pH value of RL and improved the activities of laccase-catalyzed reaction. Meanwhile, the oxidative polymerization of the side chains of RL was inhibited, caused by a radical scavenging ability of HALS. The changes in the drying process affected not only the curing time, but also the film properties. Among the 2 phr additions of different HALS, the film containing H90 had the best lightfastness. Meanwhile, it kept the most similar properties with RL and shortened the drying time of RL, and it was selected as the best HALS addition under 2 phr in this study.
Locally advanced colon cancer (LACC) is associated with surgical challenges during R0 resection, increased postoperative complications, and unfavorable treatment outcomes. Neoadjuvant concurrent ...chemoradiotherapy followed by surgical resection is an effective treatment strategy that can increase the complete surgical resection rate and improve the patient survival rate. This study investigated the efficacy and toxicity of concurrent chemoradiotherapy in patients with LACC as well as the prognosis and long-term clinical outcomes of these patients.
From January 2012 to July 2020, we retrospectively reviewed the real-world data of 75 patients with LACC who received neoadjuvant concurrent chemoradiotherapy. The chemotherapy regimen consisted of folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX). The following data were obtained from medical records: patients' characteristics, pathologic results, toxicity, and long-term oncologic outcome.
Of the 75 patients, 13 (17.3%) had pathologic complete responses. Hematologic adverse effects were the most common (grade 1 anemia: 80.0% and leukopenia: 82.7%). Conversely, grade 2 or 3 adverse effects were relatively uncommon (<10%). Pathologic N downstaging, ypT0, and pathologic complete responses were significant prognostic factors for patient survival. Multivariate analysis revealed that pathologic N downstaging was an independent predictor of patients' overall survival (P = 0.019). The estimated 5-year overall and disease-free survival rates were 68.6% and 50.6%, and the medians of overall and disease-free survival periods were 72.3 and 58.7 months, respectively. Moreover, patients with pathologic complete responses had improved overall survival (P = 0.039) and an improved local recurrence control rate (P = 0.042) but an unfavorable distant metastasis control rate (P = 0.666) in the long-term follow-up.
The long-term oncologic outcome of patients with LACC following concurrent chemoradiotherapy is acceptable, and the adverse effects seem to be tolerable. Pathologic N downstaging was an independent prognostic factor for patients' overall survival. However, a large prospective, randomized control study is required to confirm the current results.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose. The purpose of the present study was to review the literature regarding the blood loss and postoperative pain in the isolated sagittal split ramus osteotomy (SSRO) and intraoral vertical ...ramus osteotomy (IVRO). Materials and Methods. Investigating the intraoperative blood loss and postoperative pain, articles were selected from 1970 to 2021 in the English published databases (PubMed, Web of Science, and Cochrane Library). Article retrieval and selection were performed by two authors, and they independently evaluated them based on the eligibility criteria. The articles meeting the search criteria had especially at least 30 patients. Results. In the review of intraoperative blood loss, a total of 139 articles were retrieved and restricted to 6 articles (SSRO: 4; IVRO: 2). In the review of postoperative pain, a total of 174 articles were retrieved and restricted to 4 articles (SSRO: 3; IVRO: 1). The mean blood loss of SSRO and IVRO was ranged from 55 to 167 mL and 82 to 104 mL, respectively. The mean visual analog scale (VAS) scores of the first postoperative day were 2 to 5.3 in SSRO and 2.93 to 3.13 in IVRO. The mean VAS scores of the second postoperative day were 1 to 3 in SSRO and 1.1 to 1.8 in IVRO. Conclusion. Compared to traditional SSRO, IVRO had a significantly lower amount of blood loss. However, the blood transfusion is not necessary in a single-jaw operation (SSRO or IVRO). Postoperative pain was similar between SSRO and IVRO.
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