Integrative Evaluation of the Clinical Significance Underlying Protein Arginine Methyltransferases in Hepatocellular Carcinoma.

HCC is a major contributor to cancer-related mortality worldwide. Curative treatments are available for a minority of patients diagnosed at early stages; however, only a few multikinase inhibitors are available and are marginally effective in advanced cases, highlighting the need for novel therapeutic targets. One potential target is the protein arginine methyltransferase, which catalyzes various forms of arginine methylation and is often overexpressed in various cancers. However, the diverse expression patterns and clinical values of PRMTs in HCC remain unclear. In the present study, we evaluated the transcriptional expression of PRMTs in HCC cohorts using publicly available datasets. Our results revealed a significant association between PRMTs and prognosis in HCC patients with diverse clinical characteristics and backgrounds. This highlights the promising potential of PRMTs as prognostic biomarkers in patients with HCC. In particular, single-cell RNA (scRNA) sequencing analysis coupled with another human cohort study highlighted the pivotal role of PRMT1 in HCC progression, particularly in the context of Tex. Translating these findings into specific therapeutic decisions may address the unmet therapeutic needs of patients with HCC.

Synthesis of Mikto-Arm Star Peptide Conjugates.

Mikto-arm star peptide conjugates are an emerging class of self-assembling peptide-based structural units that contain three or more auxiliary segments of different chemical compositions and/or functionalities. This group of molecules exhibit interesting self-assembly behavior in solution due to their chemically asymmetric topology. Here we describe the detailed procedure for synthesis of an ABC Mikto-arm star peptide conjugate in which two immiscible entities (a saturated hydrocarbon and a hydrophobic and lipophobic fluorocarbon) are conjugated onto a short ß-sheet forming peptide sequence, GNNQQNY, derived from the Sup35 prion, through a lysine junction. Automated and manual Fmoc-solid phase synthesis techniques are used to synthesize the Mikto-arm star peptide conjugates, followed by HPLC purification. We envision that this set of protocols can afford a versatile platform to synthesize a new class of peptidic building units for diverse applications.

Supramolecular Crafting of Self-Assembling Camptothecin Prodrugs with Enhanced Efficacy against Primary Cancer Cells.

Chemical modification of small molecule hydrophobic drugs is a clinically proven strategy to devise prodrugs with enhanced treatment efficacy. While this prodrug strategy improves the parent drug's water solubility and pharmacokinetic profile, it typically compromises the drug's potency against cancer cells due to the retarded drug release rate and reduced cellular uptake efficiency. Here we report on the supramolecular design of self-assembling prodrugs (SAPD) with much improved water solubility while maintaining high potency against cancer cells. We found that camptothecin (CPT) prodrugs created by conjugating two CPT molecules onto a hydrophilic segment can associate into filamentous nanostructures in water. Our results suggest that these SAPD exhibit much greater efficacy against primary brain cancer cells relative to that of irinotecan, a clinically used CPT prodrug. We believe these findings open a new avenue for rational design of supramolecular prodrugs for cancer treatment.

Lactobacillus acidophilus modulates inflammatory activity by regulating the TLR4 and NF-κB expression in porcine peripheral blood mononuclear cells after lipopolysaccharide challenge.

A total of forty weaned pigs ((Landrace × Yorkshire) × Duroc) were used to evaluate the effects of Lactobacillus acidophilus on inflammatory activity after lipopolysaccharide (LPS) challenge. Experimental treatments were as follows: (T1) control diet+saline challenge; (T2) control diet with 0·1% L. acidophilus+saline challenge; (T3) control diet+LPS challenge; and (T4) control diet with 0·1% L. acidophilus+LPS challenge. On d-14, piglets were challenged with saline (T1 and T2) or LPS (T3 and T4). Blood samples were obtained at 0, 2, 4, 6 and 12 h after being challenged and analysed for immune cell cytokine production and gene expression pattern. The L. acidophilus treatment increased the average daily weight gain (ADWG) and average daily feed intake (ADFI) compared with the control diet. With the control diet, the LPS challenge (T3) increased the number of immune cells and expression of TNF-α and IL-6 compared with the saline challenge (T1). Whereas with the saline challenge L. acidophilus treatment (T2) increased the number of leucocytes and CD4 compared with the control diet (T1), with the LPS challenge L. acidophilus treatment (T4) decreased the number of leucocytes, lymphocytes, CD4+ and CD8+ and expression of TNF-α and IL-6 compared with the control diet (T3). L. acidophilus treatment decreased the expression of TRL4 and NF-κB in peripheral blood mononuclear cells (PBMC) after LPS challenge, which leads to inhibition of TNF-α, IFN-γ, IL-6, IL-8 and IL1B1 and to induction of IL-4 and IL-10. We suggested that L. acidophilus improved ADWG and ADFI and protected against LPS-induced inflammatory responses by regulating TLR4 and NF-κB expression in porcine PBMC.

One-component nanomedicine.

One-component nanomedicine (OCN) represents an emerging class of therapeutic nanostructures that contain only one type of chemical substance. This one-component feature allows for fine-tuning and optimization of the drug loading and physicochemical properties of nanomedicine in a precise manner through molecular engineering of the underlying building blocks. Using a precipitation procedure or effective molecular assembly strategies, molecularly crafted therapeutic agents (e.g. polymer-drug conjugates, small molecule prodrugs, or drug amphiphiles) could involuntarily aggregate, or self-assemble into nanoscale objects of well-defined sizes and shapes. Unlike traditional carrier-based nanomedicines that are inherently multicomponent systems, an OCN does not require the use of additional carriers and could itself possess desired physicochemical features for preferential accumulation at target sites. We review here recent progress in the molecular design, conjugation methods, and fabrication strategies of OCN, and analyze the opportunities that this emerging platform could open for the new and improved treatment of devastating diseases such as cancer.

Significance of Serum Testosterone for Prostate-Specific Antigen (PSA) Elevation and Prediction of Prostate Cancer in Patients with PSA Above 10 ng/ml.

PURPOSE: Testosterone is essential for the prostate gland's normal growth and development and is also a possible risk factor for prostate cancer. This study's aim was to determine the significance of serum testosterone for prostate-specific antigen (PSA) elevation and prostate cancer prediction in high-risk men. MATERIALS AND METHODS: The study included 120 patients with PSA >10 ng/ml who underwent a transrectal-prostate biopsy. Serum testosterone, prostate volume, and PSA density (PSAD) were checked in all patients. Patients were divided into two groups, patients with and those without prostate cancer; and testosterone-related factors, prostate volume, PSA, PSAD, age, prostate cancer prediction rate, and cancer aggressiveness were evaluated. RESULTS: Thirty-five patients (30.2%) were confirmed as having prostate cancer. The average serum testosterone level in patients without and in those with prostate cancer was 452.25±154.62 ng/dl and 458.10±158.84 ng/dl, respectively; average PSA was 17.58±9.02 ng/ml and 18.62±6.53 ng/ml, respectively; and average age was 69.02±7.52 years and 70.69±7.02 years, respectively (p>0.05). Hypogonadal and eugonadal patients showed no significant difference in cancer prevalence (30.3% vs. 32.0%, respectively). The testosterone level did not differ significantly in patients with and those without prostate cancer in either hypogonadal or eugonadal men (p>0.05). Serum testosterone showed no correlation with PSA, PSAD, or age in either group (p>0.05) and was unrelated to prostate cancer risk or aggressiveness (p>0.05). CONCLUSIONS: In our study's results, serum testosterone at the time of diagnosis was unrelated to PSA elevation, prostate cancer risk, and aggressiveness.