Hepatocellular carcinoma (HCC) is one of the most common and lethal malignant tumors worldwide. HCC is a complex process that is associated with several etiological factors, which in turn result in ...aberrant activation of different cellular and molecular pathways and the disruption of balance between activation and inactivation of protooncogenes and tumor suppressor genes, respectively. Since HCC most often occurs in the setting of a diseased or cirrhotic liver and most of the patients are diagnosed at the late stage of disease, prognosis is generally poor. At present, limited treatment options with marginal clinical benefits are available. Systemic therapy, particularly in the form of conventional cytotoxic drugs, are generally ineffective. In recent years, molecular-targeted therapies have been clinically used to treat various cancers, including liver cancer. This approach inhibits the growth of tumor cells by interfering with molecules that are involved in carcinogenesis, which makes it more selective and specific than cytotoxic chemotherapy. Many clinical trials have been carried out while using molecular targeted drugs in advanced HCC with many more in progress. The clinical trials in HCC to date have evaluated a single-targeted therapy alone, or two or more targeted therapies in parallel. The aim of this review is to provide insight of various molecular mechanisms, leading to HCC development and progression, and also the range of experimental therapeutics for patients with advanced HCC. The review will summarize different clinical trials data the successes and failures of these treatments, as well as the most effective and approved drugs designed against HCC.
Organic n‐type materials (e.g., fullerene derivatives, naphthalene diimides (NDIs), perylene diimides (PDIs), azaacene‐based molecules, and n‐type conjugated polymers) are demonstrated as promising ...electron transport layers (ETLs) in inverted perovskite solar cells (p–i–n PSCs), because these materials have several advantages such as easy synthesis and purification, tunable frontier molecular orbitals, decent electron mobility, low cost, good solubility in different organic solvents, and reasonable chemical/thermal stability. Considering these positive factors, approaches toward achieving effective p–i–n PSCs with these organic materials as ETLs are highlighted in this Review. Moreover, organic structures, electron transport properties, working function of electrodes caused by ETLs, and key relevant parameters (PCE and stability) of p–i–n PSCs are presented. Hopefully, this Review will provide fundamental guidance for future development of new organic n‐type materials as ETLs for more efficient p–i–n PSCs.
Organic n‐type materials as electron transport layers (ETLs) in inverted perovskite solar cells (p–i–n PSCs) have attracted many scientists' attention, not only because of their several advantages, including easy synthesis, tunable frontier molecular orbitals, decent electron mobility, and reasonable chemical/thermal stability, but also because of their ability to make large‐scale solution‐processing p–i–n PSCs possible.
Low concentrations of vanadium (V) are essential for various plant species but it becomes toxic to plants, animals, and humans at high levels. A significant amount of V is currently being emitted ...into the atmosphere due to intensified industrial processing. Therefore, this study aimed at evaluating the effect of raw (BC) and HNO3-modified biochar (OBC) derived from rice straw on growth, photosynthetic assimilation, relative chlorophyll content, SPAD index, ion leakage, enzyme activities, hydrogen peroxide (H2O2), bioavailability and V uptake by rice in a laboratory-scale experiment. Characterization of OBC and BC by FTIR (Fourier transform infrared spectroscopy), SEM (scan electron microscopy), BET (Brunauer–Emmett–Teller), elemental analysis, and z-potential revealed a substantial difference between both of them. The V-stress significantly reduced the rice plant growth, biomass yield, chlorophyll parameters, root length and surface area. Under V-stress conditions, root accumulated more V than shoots and OBC significantly improved the above-mentioned parameters, while, decreasing hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels in plants. The antioxidant function and gene expression levels induced by V-stress and OBC application further increased the expression profile of three genes (SOD, POD, and CAT) encoding antioxidant enzymes and one metal-tolerant conferring gene (OsFSD1). In summary, these results demonstrated the critical role of OBC in mitigating the detrimental effects of high V-stress on rice growth and enhancing plant defence against V-stress.
Display omitted
•High V concentration cause drastic effects on plant growth, generate oxidative stress.•Rice growth was increased with the increase in C and N contents due to modified biochar.•Oxidized biochar boosted the expression of metal tolerant genes.•Oxidized biochar illustrates the use of eco-friendly and cost-effective approach to remediate V.
Introduction and hypothesis
Most vaginal births are associated with trauma to the perineum. The morbidity associated with perineal trauma can be significant, especially when it leads to third- and ...fourth-degree perineal tears. We hypothesized that antenatal perineal massage could decrease the incidence of perineal trauma, particularly severe perineal tears and other postpartum complications.
Methods
We searched four different databases from inception until August 2019 for the available trials. We included randomized controlled trials (RCTs) which assessed the effect of antenatal perineal massage (intervention group) versus control group (no antenatal perineal massage) in perineal trauma patients. Data were extracted from eligible studies and meta-analyzed using RevMan software. Primary outcomes were the risk of episiotomies and perineal tears. Secondary outcomes were perineal pain, second stage of labor duration, wound healing, anal incontinence, and Apgar scores at 1 and 5 min.
Results
Eleven RCTs with 3467 patients were analyzed. Women who received antenatal perineal massage had significantly lower incidence of episiotomies (RR = 0.79, 95% CI 0.72, 0.87,
p
< 0.001) and perineal tears (RR = 0.79, 95% CI 0.67, 0.94,
p
= 0.007), particularly the risk of third- and fourth-degree perineal tears (
p
= 0.03). Better wound healing and less perineal pain were evident in the antenatal perineal massage group. Antenatal perineal massage reduced the second stage of labor duration (
p
= 0.005) and anal incontinence (
p
= 0.003) with significant improvement in Apgar scores at 1 and 5 min (
p
= 0.01 and
p
= 0.02).
Conclusions
Antenatal perineal massage is associated with a lower risk of severe perineal trauma and postpartum complications.
Objective
We aimed to evaluate the efficacy and safety of infliximab biosimilar, CT-P13, for patients with inflammatory bowel disease.
Methods
We searched PubMed, Scopus, Ovid, and Web of Science for ...relevant clinical trials discussing CT-P31 administration for IBD patients either naïve to biological therapy or switched from IFX therapy. Data of the rates of clinical response, clinical remission, and adverse events were extracted and pooled in a random effect model meta-analysis using CMA version 2.
Results
Thirty-two studies with a total of 3464 IBD patients treated with CT-P13 were identified. The pooled rates of clinical response among Crohn’s disease (CD) and ulcerative colitis (UC) at 8–14 weeks were 0.81 (95% CI = 0.72 to 0.87) and 0.68 (95% CI = 0.63 to 0.72), respectively, and at 48–63 weeks were 0.69 (95% CI = 0.48 to 0.85) and 0.54 (95% CI = 0.45 to 0.63) respectively. After switching from IFX to CT-P13, the pooled rates of sustained clinical response among CD and UC at 30–32 weeks were 0.84 (95% CI = 0.57 to 0.96) and 0.96 (95% CI = 0.58 to 0.99), respectively, and at 48–63 weeks were 0.51 (95% CI = 0.22 to 0.79) and 0.83 (95% CI = 0.19 to 0.99) respectively. Moreover, adverse events were reported (CD = 0.10, 95% CI 0.04 to 0.22; UC = 0.18, 95% CI 0.05 to 0.15).
Conclusion
CT-P13 is effective and well tolerated in short and long-term periods. Switching to CT-P13 is recommended for the management of IBD.
Background and aims So far, few clinical trials are available concerning the role of growth hormone receptor (GHR)/signal transducer and activator of transcription 5 (STAT5)/insulin like growth ...factor-1 (IGF-1) axis in hepatocarcinogenesis. The aim of this study was to evaluate the hepatic expression of GHR/STAT5/IGF-1 signaling pathway in hepatocellular carcinoma (HCC) patients and to correlate the results with the clinico-pathological features and disease outcome. The interaction between this signaling pathway and some inducers of epithelial-mesenchymal transition (EMT), namely Snail-1 and type 2 transforming growth factor-beta receptor (TGFBR2) was studied too. Material and methods A total of 40 patients with HCV-associated HCC were included in this study. They were compared to 40 patients with HCV-related cirrhosis without HCC, and 20 healthy controls. The hepatic expression of GHR, STAT5, IGF-1, Snail-1 and TGFBR2 proteins were assessed by immunohistochemistry. Results Compared with cirrhotic patients without HCC and healthy controls, cirrhotic patients with HCC had significantly lower hepatic expression of GHR, STAT5, and IGF-1proteins. They also displayed significantly lower hepatic expression of TGFBR2, but higher expression of Snail-1 versus the non-HCC cirrhotic patients and controls. Serum levels of alpha-fetoprotein (AFP) showed significant negative correlations with hepatic expression of GHR (r = -0.31; p = 0.029) and STAT5 (r = -0.29; p = 0.04). Hepatic expression of Snail-1 also showed negative correlations with GHR, STAT5, and IGF-1 expression (r = -0.55, p = 0.02; r = -0.472, p = 0.035, and r = -0.51, p = 0.009, respectively), whereas, hepatic expression of TGFBR2 was correlated positively with the expression of all these proteins (r = 0.47, p = 0.034; 0.49, p = 0.023, and r = 0.57, p100 ng/ml (p = 0.048), increased tumor size (p = 0.02), vascular invasion (p = 0.002), and advanced pathological stage (p = 0.01). Similar significant associations were found between down-regulation of STAT5 expression and AFP level > 100 ng/ml (p = 0.006), vascular invasion (p = 0.009), and advanced tumor stage (p = 0.007). Also, attenuated expression of IGF-1 showed a significant association with vascular invasion (p < 0.001). Intriguingly, we detected that lower expression of GHR, STAT5 and IGF-1 were considered independent predictors for worse outcome in HCC. Conclusion Decreased expression of GHR/STAT5/IGF-1 signaling pathway may have a role in development, aggressiveness, and worse outcome of HCV-associated HCC irrespective of the liver functional status. Snail-1 and TGFBR2 as inducers of EMT may be key players. However, large prospective multicenter studies are needed to validate these results.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A Schiff base ligand of o-vanillin and 4-aminoazobenzene and its transition metal complexes of Ni(II), Co(II), Zn(II), Cu(II), Mn(II), and Zr(IV) were prepared under microwave irradiation as a ...green approach compared to the conventional method. The structures of new compounds have been characterized and elucidated via elemental and spectroscopic analyses. In addition, magnetic susceptibility, electron spin resonance, and electronic spectra of the synthesized complexes explained their geometrical structures. The thermal stability of Cu(II), Zn(II), and Zr(IV) complexes was studied by thermo-gravimetric analyses (TGA). Coats–Redfern and Horowitz–Metzger equations were used to calculate the thermal and dehydration decomposition activities of proposed structures kinetically. Surface morphologies of the solid compounds were imaged by scanning electron microscopy (SEM). The particle size of prepared complexes was measured by using a particle size analyzer at a diffraction angle of 10.9°. The geometry structures of the synthesized compounds were verified utilizing electronic spectra, ESR spectrum, and magnetic moment value. The newly synthesized compounds were screened for antimicrobial activity. Also, the anticancer activity of the free Schiff base ligand and its metal complexes were studied against two cell lines: human colon (HCT-116) and human liver cancer cells (HepG-2). The obtained results showed that the Cu(II) complex displayed the highest cytotoxic activity (IC50 = 18 and 22 μg/mL for HepG-2 and HCT, respectively) compared to the free Schiff base ligand.
Key Clinical Message
Bilateral thalamic infarction in paramedian artery territory may present with severe acute illness, confusion, coma and memory impairment. However, subtle clinical presentation ...as in our case should alert the clinician to consider such a diagnosis as it can be associated with good prognosis.
Bilateral thalamic infarct is a rare form of stroke. Mostly thalamic infarcts are unilateral. In most cases, bilateral thalamic infarction leads to cognitive dysfunction, opthalmoparesis, conscious impairment, behavioral disturbance, and corticospinal dysfunction. Here, we describe the case of a 75‐year‐old male patient who presented to the emergency department of our hospital with agitation and somnolence for one day. He had poorly controlled hypertension. There was no previous history of stroke, diabetes mellitus, hyperlipidemia, known cardiac disease, or smoking history. There was no seizure, recent headache, or visual disturbance. The patient was somnolent and not oriented to time, person, or place. Neurological examination did not show any focal weakness or vertical eye movement restrictions. Other systemic examinations, including those of the respiratory and cardiovascular systems, were unremarkable. Extensive laboratory investigations excluded potential metabolic, infectious, endocrine, or toxic etiologies. The patient did not have any recent history of drug misuse, including benzodiazepines. Brain MRI with diffusion‐weighted imaging showed an acute bilateral thalamic infarct. Cerebral angiography was unremarkable. The patient was treated with low molecular weight heparin 60 mg subcutaneously, aspirin 300 mg daily, and haloperidol 5 mg twice daily for agitation. After two weeks of intrahospital treatment, his condition improved (consciousness and orientation massively improved).
Organic–inorganic perovskite solar cells (PSCs) have been emerging as one of the most promising photovoltaic technologies. Surface morphology is considered as a key-parameter in energy alignment and ...plays a dominant role in specifying the device performance. The large grains and low roughness enhance the transport of charge carriers from perovskite layers to the transport layers, and this reflects on the delivered power conversion efficiency (PCE). Therefore, in this study, we investigated the influence of the fabrication parameters on the grain size and the morphology of perovskite layers, thereby the PCE of PSCs. These parameters included the anti-solvent nature (chlorobenzene or toluene), annealing temperature, and annealing ramp rate (slow or flash annealing). The scanning electron microscope confirmed that flash annealing results in a better morphology than slow annealing whether by employing an anti-solvent dripping or not. Furthermore, the dripping of chlorobenzene as an anti-solvent produced better morphology and large grains compared with toluene. Therefore, combining chlorobenzene with flash annealing induced the formation of large grains, full cover, and a uniform perovskite layer, which reflects on the performance of the fabricated PSCs. Finally, employing the aforementioned optimum preparation parameters to fabricate carbon-based PSCs resulted in decent PCE, current density short circuit (Jsc), open circuit voltage (Voc), and fill factor (FF) of 7%, 11.3 mA/cm2, 0.74 V, and 34%, respectively.
Five new compounds
kaempferol 3-
-(4″-galloyl)-
-d-glucopyranosyl-(1‴→6″)-
-β-d-glucopyranoside (
), kaempferol 3-
-
-d-mannuronopyranoside (
), kaempferol 3-
-
-d-mannopyranoside (
), quercetin 3-
-
...-d-mannuronopyranoside (
), 2, 3 (S)- hexahydroxydiphenoyl-d-glucose (
) along with fifteen known compounds were isolated from 80% aqueous methanol extract (AME) of
. AME and compounds exerted similar or better antioxidant activity to ascorbic acid using DPPH, O
, and NO inhibition methods. In addition, compounds
,
, and
showed cytotoxic activity against MCF-7 cell lines while
,
and
exhibited strong activity against HepG2. An in silico analysis using molecular docking for polyphenolic compounds
,
,
,
and
against human stable 5-LOX was performed and compared to that of ascorbic acid and quercetin. The binding mode as well as the enzyme-inhibitor interactions were evaluated. All compounds occupied the 5-LOX active site and showed binding affinity greater than ascorbic acid or quercetin. The data herein suggest that AME, a source of polyphenols, could be used against oxidative-stress-related disorders.
PDF
