UCHL1/PGP 9.5 Dynamic in neuro-immune-cutaneous milieu : focusing on axonal nerve terminals and epidermal keratinocytes in psoriatic itch

Psoriasis is an immunogenetic skin disease manifesting as plaque lesions on the skin. Patients with psoriasis frequently suffer from itch, an unpleasant sensation causing a desire to scratch. Psoriatic itch is mainly transmitted by unmyelinated C-fibers; however, the exact molecular mechanism of psoriatic itch is still unexplained. Protein gene product 9.5 (PGP 9.5) is a panneurological marker commonly used for analysis of peripheral peptidergic and nonpeptidergic nerves and identification of cutaneous neuro-immune-endocrine cells. However, some studies suggested that nonneuronal cells, like keratinocytes, may also express PGP 9.5. This phenomenon might be linked with impaired axonal transport, keratinocyte injury, or dysfunctions of neuro-immune-cutaneous connections. The aim of this study was to analyze the expression of PGP 9.5 in psoriatic skin. We observed significantly altered density of PGP 9.5-positive axonal nerve terminals in pruritic lesional (p=0.04) and nonlesional psoriatic skin (p>0.001) compared with controls. In contrast, no significant differences were observed between psoriatic skin without itch and controls. Furthermore, PGP 9.5 expression by suprabasal keratinocytes (SBKs) was significantly increased in itchy skin lesions (p=0.007) compared to skin without itch, and a positive correlation was observed between PGP 9.5 expression and itch intensity (r=0.64; p=0.02). Our findings indicate changes in peripheral innervations and psoriatic keratinocytes, which may influence neuro-immune-cutaneous homeostasis and modulate itch transmission

Complexity of the Genetic Background of Oncogenesis in Ovarian Cancer—Genetic Instability and Clinical Implications

Ovarian cancer is a leading cause of death among women with gynecological cancers, and is often diagnosed at advanced stages, leading to poor outcomes. This review explores genetic aspects of high-grade serous, endometrioid, and clear-cell ovarian carcinomas, emphasizing personalized treatment approaches. Specific mutations such as TP53 in high-grade serous and BRAF/KRAS in low-grade serous carcinomas highlight the need for tailored therapies. Varying mutation prevalence across subtypes, including BRCA1/2, PTEN, PIK3CA, CTNNB1, and c-myc amplification, offers potential therapeutic targets. This review underscores TP53’s pivotal role and advocates p53 immunohistochemical staining for mutational analysis. BRCA1/2 mutations’ significance as genetic risk factors and their relevance in PARP inhibitor therapy are discussed, emphasizing the importance of genetic testing. This review also addresses the paradoxical better prognosis linked to KRAS and BRAF mutations in ovarian cancer. ARID1A, PIK3CA, and PTEN alterations in platinum resistance contribute to the genetic landscape. Therapeutic strategies, like restoring WT p53 function and exploring PI3K/AKT/mTOR inhibitors, are considered. The evolving understanding of genetic factors in ovarian carcinomas supports tailored therapeutic approaches based on individual tumor genetic profiles. Ongoing research shows promise for advancing personalized treatments and refining genetic testing in neoplastic diseases, including ovarian cancer. Clinical genetic screening tests can identify women at increased risk, guiding predictive cancer risk-reducing surgery

Old and new face of aspirin

Salicylic acid has been known as a therapeutic substance since antiquity. Since its inception, acetylsalicylic acid, i.e. its original acetylated derivative, has become one of the most popular analgesic substances. Over the years, it has gained the recognition of cardiologists, and its potential antineoplastic effects have been recently studied. By inhibiting cyclooxygenase 2 (COX-2), the drug reduces the formation of prostaglandins, which relieves inflammation, eases swelling and lowers fever. Moreover, aspirin has an anticoagulant effect owing to its inhibition of cyclooxygenase 1 (COX-1). The prophylactic outcome of acetylsalicylic acid in patients with cardiovascular diseases is undeniable, but its benefits in individuals without cardiac disease are controversial. However, research is ongoing to identify the group of beneficiaries of primary prevention precisely, and the results are expected in the near future. Another field of action of acetylsalicylic acid which is currently under investigation is related to the potential antineoplastic effect of the drug. Nowadays, most of the data indicate its positive effects in patients with a positive history of colorectal proliferative diseases. The antineoplastic activity of the drug is based on the inhibition of COX-2, an enzyme stimulating cell divisions. Therefore, the effect of the medicine may be visible in tumours characterised by an overexpression of this enzyme. A positive response to aspirin also depends on the human genome and specific mutations in cancer cells. By acting on platelet COX-1, aspirin reduces the metastatic potential of cancer, as platelet-derived substances promote the formation of metastases. To sum up, only a selected group of patients exhibit sensitivity to the anticancer effects of the drug. Nevertheless, the use of aspirin could turn out to be dangerous in people with a high risk of complications, so each patient should be treated individually.Kwas salicylowy jako substancja lecznicza był znany już w starożytności. Odkąd powstał kwas acetylosalicylowy (potocznie zwany później aspiryną) – jego oryginalna acetylowana pochodna – lek ten stał się jedną z najpopularniejszych substancji przeciwbólowych. W miarę upływu lat zyskał on uznanie kardiologów, a ostatnio badane jest jego potencjalne działanie przeciwnowotworowe. Aspiryna poprzez inhibicję cyklooksygenazy 2 (COX-2) zmniejsza powstawanie prostaglandyn, co ogranicza stan zapalny, zmniejsza obrzęk oraz zwalcza gorączkę, a dzięki hamującemu wpływowi na cyklooksygenazę 1 (COX-1) działa antykoagulacyjnie. Profilaktyczne działanie kwasu acetylosalicylowego u osób obciążonych chorobami układu sercowo-naczyniowego jest niepodważalne, natomiast kontrowersyjne jest jego stosowanie u osób nieobciążonych kardiologicznie. Trwają jednak badania mające na celu definitywne określenie grupy beneficjentów profilaktyki pierwotnej. Wyniki będą znane w najbliższej przyszłości. Kolejnym obecnie badanym polem działania kwasu acetylosalicylowego jest jego potencjalne działanie przeciwnowotworowe. Obecnie najwięcej danych wskazuje na jego pozytywny wpływ u osób z dodatnim wywiadem w kierunku chorób rozrostowych jelita grubego oraz odbytnicy. Działanie antyproliferacyjne leku polega na hamowaniu COX-2, która pobudza podziały komórkowe. Dlatego też efekt jego działania może być widoczny w nowotworach cechujących się zwiększoną ekspresją tego enzymu. Pozytywna odpowiedź na aspirynę zależy od genomu danej osoby, jak również od określonych mutacji w komórkach nowotworowych. Lek ten, działając na płytkową COX-1, zmniejsza potencjał metastatyczny raka, gdyż substancje pochodzące z płytek krwi promują powstawanie przerzutów. Reasumując, można stwierdzić, że tylko wybrana grupa pacjentów jest wrażliwa na przeciwnowotworowe działanie kwasu acetylosalicylowego, a u osób z dużym ryzykiem powikłań jego stosowanie mogłoby się okazać niebezpieczne, dlatego do przypadku każdego chorego należy podchodzić indywidualnie

Transcript level of AKR1C3 is down-regulated in gastric cancer

Steroid hormones are shown to play some role in gastric carcinogenesis. Large amounts of them are locally produced in peripheral tissues at both genders. Type 5 of 17β-hydroxysteroid dehydrogenase, encoded by AKR1C3 gene, plays a pivotal role in both androgen and estrogen metabolism and its deregulated expression was found in different cancers. In this study we measured AKR1C3 transcript and protein levels in nontumoral and primary tumoral gastric tissues and evaluated their association with some clinicopathological features of gastric cancer (GC). We found decreased AKR1C3 transcript (pThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Elemental and mineralogical analysis of marine and coastal sediments from Phra Thong Island, Thailand: Insights into the provenance of coastal hazard deposits

Sediment records left by coastal hazards (e.g. tsunami and/or storms) may shed light on the sedimentary and hydrodynamic processes happening during such events. Modern onshore and offshore sediment samples were compared with the 2004 Indian Ocean Tsunami, three palaeotsunami and a 2007 storm deposit from Phra Thong Island, Thailand, to determine provenance relationships between these coastal overwash deposits. Sedimentological and stratigraphic characteristics are generally inadequate to discriminate tsunami and storm deposits so a statistical approach (including cluster analysis, principal component analysis and discriminant function analysis) was used based on grain size, mineralogy and trace element geochemistry. The mineral content and trace element geochemistry are statistically inadequate to distinguish the provenance of the modern storm and tsunami deposits at this site, but the mean grain size can potentially discriminate these overwash deposits. The 2007 storm surge deposits were most likely sourced from the onshore sediment environment whereas all four tsunami units statistically differ from each other indicating diverse sediment sources. Our statistical analyses suggest that the 2004 tsunami deposit was mainly derived from nearshore marine sediments. The uppermost palaeotsunami deposit was possibly derived from both onshore and nearshore materials while the lower palaeotsunami deposits showed no clear evidence of their sediment sources. Such complexity raises questions about the origin of the sediments in the tsunami and storm deposits and strongly suggests that local context and palaeogeography are important aspects that cannot be ignored in tsunami provenance studies

Combined Effects of Methyldopa and Baicalein or <i>Scutellaria baicalensis</i> Roots Extract on Blood Pressure, Heart Rate, and Expression of Inflammatory and Vascular Disease-Related Factors in Spontaneously Hypertensive Pregnant Rats

The aim of the study was to investigate the effect of baicalein or Scutellaria baicalensis root extract interaction with methyldopa in pregnant spontaneously hypertensive rats (SHR) at the pharmacodynamic, molecular, and biochemical levels. The rats, after confirming pregnancy, received baicalein (200 mg/kg/day, p.o.) and extract (1000 mg/kg/day, p.o.), in combination with methyldopa (400 mg/kg/day; p.o.), for 14 consecutive days, 1 h before blood pressure and heart rate measurements. In the heart and placenta from mothers after giving birth to their offspring, mRNA expression of factors related to inflammatory processes (TNF-α, Il-1β, IL-6) and vascular diseases (TGF-β, HIF-1α, VEGF, PlGF) was measured. Levels of markers of oxidative stress (superoxide dismutase and malondialdehyde) in the placenta and indicators of myocardial damage (troponin cTnC and cTnI, creatine kinase, myoglobin, and lactate dehydrogenase) in the heart were also assessed. Baicalein co-administered with methyldopa was associated with reduced blood pressure, especially during the first three days. The interactions were more pronounced for such factors as TGF-β, HIF-1α, VEGF, and PlGF than TNF-α, Il-1β, and IL-6. Combined application of baicalein and extract with methyldopa may be of value in the development of a new antihypertensive medication intended for patients suffering from preeclampsia or pregnancy-induced hypertension