PIEZO1 activation may serve as an early tissue biomarker for the prediction of irradiation-induced salivary gland dysfunction.

Irradiation (IR)-induced xerostomia is the most common side effect of radiation therapy in patients with head and neck cancer (HNC). Xerostomia diagnosis is mainly based on the patient's medical history and symptoms. Currently, no direct biomarkers are available for the early prediction of IR-induced xerostomia. Here, we identified PIEZO1 as a novel predictive tissue biomarker for xerostomia. Our data demonstrate that PIEZO1 is significantly upregulated at the gene and protein levels during IR-induced salivary gland (SG) hypofunction. Notably, PIEZO1 upregulation coincided with that of inflammatory (F4/80) and fibrotic markers (fibronectin and collagen fibers accumulation). These findings suggest that PIEZO1 upregulation in SG tissue may serve as a novel predictive marker for IR-induced xerostomia.

Survival Outcome and Prognostic Factors Among Patients With Hepatocellular Carcinoma: A Hospital-Based Study.

Background: Hepatocellular carcinoma (HCC) is a leading cancer with very high incidence and mortality and low survival rate in Vietnam and worldwide. This study aimed to investigate the survival outcome and its prognostic factors among HCC patients. Methods: This is a retrospective descriptive study on patients newly diagnosed with HCC at Hanoi Oncology Hospital, Vietnam from January 2018 to December 2020. Overall survival (OS) was calculated by the Kaplan-Meier method. Log-rank test and Cox regression were used to investigate the association among patients' OS and their diagnosis and treatment factors. Results: A total of 674 patients were included. The median OS was 10.0 months. The survival rates at 6, 12, 24, and 36 months were 57.3%, 46.6%, 34.8%, and 29.7%, respectively. The initial performance status (PS), Child-Pugh score, and Barcelona Clinic Liver Cancer (BCLC) stage at the time of diagnosis are prognostic factors of HCC OS. A total of 451 (66.8%) patients have died, most of them (375 equally 83.1%) died at home, and only 76 (16.9%) died at hospital. Hepatocellular carcinoma patients living in the rural area more likely died at home than those living in the urban area (85.9% vs 74.8%, P = .007). Conclusions: Hepatocellular carcinoma has a poor prognosis with low OS. Performance status, Child-Pugh score, and BCLC stage were the independent prognostic factors for the survival outcome of HCC patients. The fact that most HCC patients died at home suggested that home-based hospice care needs to be paid special attention.

GmDREB6, a soybean transcription factor, notably affects the transcription of the NtP5CS and NtCLC genes in transgenic tobacco under salt stress conditions.

Soil is contaminated with salinity, which inhibits plant growth and development and reduces crop yields. The DREB (dehydration responsive element binding protein) gene responds to salt stresses through enhanced transcriptional expression and activation of genes involved in plant salinity resistance. In this study, we present the results of the analysis of the expression of the GmDREB6 transgene, a gene that encodes the soybean DREB6 transcription factor, regulating the transcription of the NtP5CS and NtCLC genes in transgenic tobacco under salt stress conditions. The transcription of GmDREB6, NtP5CS, and NtCLC in transgenic tobacco lines was confirmed by qRT-PCR. Under salt stress conditions, the GmDREB6 gene transcription levels in the transgenic tobacco lines L1 and L9 had increased from 2.40- to 3.22- fold compared with the condition without salinity treatment. Two transgenic lines, L1 and L9, had transcription levels of the P5CS gene that had increased from 1.24- to 3.60- fold compared with WT plants. For the NtCLC gene, under salt stress conditions, the transgenic lines had transcription levels that had increased by 3.65-4.54 (fold) compared with WT plants (P < 0.05). The L1-transgenic tobacco line showed simultaneous expression of both the GmDREB6 transgene and two intrinsic genes, the NtP5CS and NtCLC genes. This study demonstrated that expression of the GmDREB6 gene from soybean increases the transcription levels of the NtP5CS and NtCLC genes in transgenic tobacco plants under salt stress conditions. The analysis results have suggested that the GmDREB6 gene is a potential candidate for improving the salt tolerance of plants, opening up research and development opportunities for salt stress-tolerant crops to respond to climate change and the rise in sea levels.

Natural oil blend formulation as an anti-African swine fever virus agent in in vitro primary porcine alveolar macrophage culture.

BACKGROUND AND AIM: African swine fever is one of the severe pathogens of swine. It has a significant impact on production and economics. So far, there are no known remedies, such as vaccines or drugs, reported working successfully. In the present study, the natural oil blend formulation's (NOBF) efficacy was evaluated against ASFV in vitro using porcine alveolar macrophages (PAMs) cells of swine. MATERIALS AND METHODS: The capacity of NOBF against the ASFV was tested in vitro. The NOBF combines Eucalyptus globulus, Pinus sylvestris, and Lavandula latifolia. We used a 2-fold serial dilution to test the NOBF formulation dose, that is, 105 HAD50/mL, against purified lethal dose of African swine in primary PAMs cells of swine. The PAM cells survival, real-time polymerase chain reaction (PCR) test, and hemadsorption (HAD) observation were performed to check the NOBF efficacy against ASFV. RESULTS: The in vitro trial results demonstrated that NOBF up to dilution 13 or 0.000625 mL deactivates the lethal dose 105 HAD50 of ASFV. There was no HAD (Rosetta formation) up to dilution 12 or 0.00125 mL of NOBF. The Ct value obtained by running real-time PCR of the NOBF group at 96 h post-infection was the same as the initial value or lower (25), whereas the Ct value of positive controls increased several folds (17.84). CONCLUSION: The in vitro trial demonstrated that NOBF could deactivate the ASFV. The NOBF has the potential to act as anti-ASFV agent in the field. The next step is to conduct in vivo level trial to determine its efficacy.

Survival in resectable pancreatic ductal adenocarcinoma with para-aortic lymph node dissection: A retrospective study in Vietnamese population.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a high recurrence rate and poor outcome. Lymph node (LN) metastasis, especially para-aortic LN (PALN), is an important prognostic factor. PALN assessment through sampling with frozen-section analysis is a validated method. Our aim was to evaluate the prognostic impact of PALN on overall survival (OS) in patients who underwent standard pancreaticoduodenectomy, lymphadenectomy with PALN sampling, as well as to identify other prognostic factors for survival. METHODS: Our retrospective study included 89 PDAC patients undergoing radical resection with PALN sampling. The patients were classified into PALN(+) (n = 11) and PALN(-) (n = 78). Univariate and multivariate analyses of 1-year and 3-year OS and Kaplan-Meier model were used. RESULTS: OS after 1-year for PALN(+) and PALN(-) was 18.2 and 56.4%, after 3-year was 15.4% and 0%, respectively. Tumor differentiation, LN metastasis (LN(-), LN(+) PALN(-), LN(+) PALN(+)) were significant prognostic factors in both univariate and multivariate analyses for 1-year OS, and neural invasion (PN) was the solely significant factor for 3-year OS (p < 0.05). Kaplan-Meier estimate showed that OS of PALN(+) and PN (+) was significantly lower than the negative group, respectively (p < 0.05). No statistical difference in OS was seen between LN(-) and LN(+) PALN(-); and between LN(+) PALN(-) and PALN(+) (p = 0.107). Patients with PN (-) PALN(+) had similar OS compared to PN (+) PALN(-) (p > 0.05). CONCLUSION: PDAC had a poor outcome despite treatment with radical resection. Further follow-up should be conducted to determine the role of surgery in PALN(+)and PN invasion.

Treatment of complex complications after choledochal cyst resection by multiple minimal invasive therapies: A case report.

INTRODUCTION: Choledochal cyst is a rare benign congenital dilation of the bile duct, which causes recurring disturbing symptoms without totally resection. Nonetheless, postoperative complications are still a common issue. A step up management for patients with complex complications is required to address the problem. CASE PRESENTATION: We report a 10-year-old child who suffered complex postoperative complications after choledochal cyst resection at the age of 5, including cholangitis, bilioenteric stenosis and cystolithiasis in remnant intrapancreatic duct cyst. She occasionally endured episodes of epigastric pain, fever and jaundice afterwards. As the symptoms and recurrent rate were worsen over time, the patient was admitted multiple times and various approaches (balloon dilation, percutaneous transhepatic biliary drainage, endoscopic retrograde cholangiopancreatography and laparoscopic surgery) were applied. Afterwards, patient recovered and discharged without any complications. CONCLUSION: Our case presented sophisticated complications relating to choledochal cyst that were successfully treated by a combination of modern minimal invasive techniques. Despite operated by experienced surgeons, the post-op complications are still a concerned problem due to difficult laparoscopic techniques, injuries of hepatic artery, infection and risk of malignancy. We suggested that minimal-invasive procedures should be considered first with the aim of relieving symptoms, biliary drainage and preparing for the reoperation.

Transferrin-conjugated pH-sensitive platform for effective delivery of porous palladium nanoparticles and paclitaxel in cancer treatment.

Porous palladium (Pd) nanoparticles have garnered great research attention due to their potential anticancer activity and photothermal effect. In this study, a transferrin-conjugated pH-sensitive platform (Tf-PPP), comprising porous Pd nanoparticles (PdNPs) and paclitaxel (PTX), was successfully developed for combined chemo-phototherapy. Tf-PPPs have a small size of 164.6 ± 8.7 nm, PDI of 0.278 ± 0.029, and negative charge (-13.2 ± 1.8 mV). Poly(acrylic acid)-poly(ethylene oxide) (PAA-PEO), a pH sensitive polymer, was used to achieve pH-dependent drug release from nanoparticles. Transferrin (Tf) conjugated on the surface of nanoplatforms could enhance the cellular uptake and prolong nanoparticle accumulation in the tumor site. The combination of phototherapy induced by PdNPs and chemotherapeutic agent (PTX) could exhibit synergistic anticancer activities. Consistent findings were observed in both in vitro experiments including cytotoxicity, live/dead assay, and assessment of apoptotic protein levels, and in vivo antitumor study in MCF-7 tumor-bearing mice, with results decreasing in the following order: Tf-PPPs + NIR > Tf-PPPs > PPPs + NIR > PPPs > PTX > PdNPs. These findings suggest that the administration of Tf-PPPs, followed by NIR irradiation could be a promising strategy in the treatment of cancer.

The role of thiamine in cancer: possible genetic and cellular signaling mechanisms.

The relationship between supplemental vitamins and various types of cancer has been the focus of recent investigation, and supplemental vitamins have been reported to modulate cancer rates. A significant association has been demonstrated between cancer and low levels of thiamine in the serum. Genetic studies have helped identify a number of factors that link thiamine to cancer, including the solute carrier transporter (SLC19) gene, transketolase, transcription factor p53, poly(ADP-ribose) polymerase-1 gene, and the reduced form of nicotinamide adenine dinucleotide phosphate. Thiamine supplementation may contribute to a high rate of tumor cell survival, proliferation and chemotherapy resistance. Thiamine has also been implicated in cancer through its effects on matrix metalloproteinases, prostaglandins, cyclooxygenase-2, reactive oxygen species, and nitric oxide synthase. However, some studies have suggested that thiamine may exhibit some antitumor effects. The role of thiamine in cancer is controversial. However, thiamine deficiency may occur in patients with cancer and cause serious disorders, including Wernicke's encephalopathy, that require parenteral thiamine supplementation. A very high dose of thiamine produces a growth-inhibitory effect in cancer. Therefore, further investigations of thiamine in cancer are needed to clarify this relationship.

The beneficial role of vitamin D in obesity: possible genetic and cell signaling mechanisms.

The prevalence rates of overweight and obesity are considered an important public issue in the United States, and both of these conditions are increasing among both children and adults. There is evidence of aberrations in the vitamin D-endocrine system in obese subjects. Vitamin D deficiency is highly prevalent in patients with obesity, and many studies have demonstrated the significant effect of calcitriol on adipocytes. Genetic studies have provided an opportunity to determine which proteins link vitamin D to obesity pathology, including the vitamin D receptor, toll-like receptors, the renin-angiotensin system, apolipoprotein E, vascular endothelial growth factor, and poly (ADP-ribose) polymerase-1. Vitamin D also exerts its effect on obesity through cell-signaling mechanisms, including matrix metalloproteinases, mitogen-activated protein kinase pathways, the reduced form of nicotinamide adenine dinucleotide phosphate, prostaglandins, reactive oxygen species, and nitric oxide synthase.In conclusion, vitamin D may have a role in obesity. The best form of vitamin D for use in the obese individuals is calcitriol because it is the active form of the vitamin D3 metabolite, its receptors are present in adipocytes, and modulates inflammatory cytokine expression.

The role of ß-adrenergic blockers in Parkinson's disease: possible genetic and cell-signaling mechanisms.

Genetic studies have identified numerous factors linking ß-adrenergic blockade to Parkinson's disease (PD), including human leukocyte antigen genes, the renin-angiotensin system, poly(adenosine diphosphate-ribose) polymerase 1, nerve growth factor, vascular endothelial growth factor, and the reduced form of nicotinamide adenine dinucleotide phosphate. ß-Adrenergic blockade has also been implicated in PD via its effects on matrix metalloproteinases, mitogen-activated protein kinase pathways, prostaglandins, cyclooxygenase 2, and nitric oxide synthase. ß-Adrenergic blockade may have a significant role in PD; therefore, the characterization of ß-adrenergic blockade in patients with PD is needed.

The role of Beta-adrenergic receptor blockers in Alzheimer's disease: potential genetic and cellular signaling mechanisms.

According to genetic studies, Alzheimer's disease (AD) is linked to beta-adrenergic receptor blockade through numerous factors, including human leukocyte antigen genes, the renin-angiotensin system, poly(adenosine diphosphate-ribose) polymerase 1, nerve growth factor, vascular endothelial growth factor, and the reduced form of nicotinamide adenine dinucleotide phosphate. Beta-adrenergic receptor blockade is also implicated in AD due to its effects on matrix metalloproteinases, mitogen-activated protein kinase pathways, prostaglandins, cyclooxygenase-2, and nitric oxide synthase. Beta-adrenergic receptor blockade may also have a significant role in AD, although the role is controversial. Behavioral symptoms, sex, or genetic factors, including Beta 2-adrenergic receptor variants, apolipoprotein E, and cytochrome P450 CYP2D6, may contribute to beta-adrenergic receptor blockade modulation in AD. Thus, the characterization of beta-adrenergic receptor blockade in patients with AD is needed.

The beneficial role of vitamin D in systemic lupus erythematosus (SLE).

Patients with systemic lupus erythematosus (SLE) have a high prevalence of abnormal bone metabolism and vitamin D deficiency. Genetic studies have provided the opportunity to determine the specific proteins linking vitamin D to SLE pathology [i.e., major histocompatibility complex (MHC) class II molecules, the vitamin D receptor (VDR), microRNAs (miRNAs), the renin-angiotensin system (RAS), apolipoprotein E (ApoE), liver X receptor (LXR), and toll-like receptors (TLRs)]. Vitamin D also exerts protective effects against SLE through non-genomic factors, such as ultraviolet radiation (UV) exposure, matrix metalloproteinase (MMPs), heme oxygenase-1 (HO-1), the prostaglandins (PGs), cyclooxygenase-2 (COX-2), and oxidative stress. Thus, vitamin D may play a beneficial role in SLE. Moreover, the use of calcitriol or 1α,25-dihydroxyvitamin D(3) is optimal for the treatment of SLE patients because this active form of the vitamin D(3) metabolite can modulate inflammatory cytokine production. However, further investigation into the effects of calcitriol with SLE is warranted.

The roles of beta-adrenergic receptors in tumorigenesis and the possible use of beta-adrenergic blockers for cancer treatment: possible genetic and cell-signaling mechanisms.

Cancer is the leading cause of death in the USA, and the incidence of cancer increases dramatically with age. Beta-adrenergic blockers appear to have a beneficial clinical effect in cancer patients. In this paper, we review the evidence of an association between ß-adrenergic blockade and cancer. Genetic studies have provided the opportunity to determine which proteins link ß-adrenergic blockade to cancer pathology. In particular, this link involves the major histocompatibility complex class II molecules, the renin-angiotensin system, transcription factor nuclear factor-kappa-light-chain-enhancer of activated B cells, poly(ADP-ribose) polymerase-1, vascular endothelial growth factor, and the reduced form of nicotinamide adenine dinucleotide phosphate oxidase. Beta-adrenergic blockers also exert anticancer effects through non-genomic factors, including matrix metalloproteinase, mitogen-activated protein kinase pathways, prostaglandins, cyclooxygenase-2, oxidative stress, and nitric oxide synthase. In conclusion, ß-adrenergic blockade may play a beneficial role in cancer treatment. Additional investigations that examine ß-adrenergic blockers as cancer therapeutics are required to further elucidate this role.

The beneficial role of vitamin D and its analogs in cancer treatment and prevention.

BACKGROUND: Cancer is the leading cause of death in the United States, and the probability of developing cancer increases dramatically with age. Interestingly, vitamin D deficiency is also recognized more often in people of advanced ages. A potential relationship between vitamin D deficiency and cancer has been reported in the literature. METHOD: Review Medline database literature and discuss the relationship between vitamin D status and cancer. RESULTS: Environmental (including seasonal and geographic) and genetic factors contribute to the development of both vitamin D deficiency and cancer. The vitamin D receptor is present in many tissues, especially in malignant cells, and may contribute to the successful use of vitamin D and its analogs in the treatment of some cancer patients. CONCLUSION: Further investigation of the role of vitamin D in the treatment of cancer is warranted.