Biomedical Trends in Stimuli-Responsive Hydrogels with Emphasis on Chitosan-Based Formulations.

Biomedicine is constantly evolving to ensure a significant and positive impact on healthcare, which has resulted in innovative and distinct requisites such as hydrogels. Chitosan-based formulations stand out for their versatile utilization in drug encapsulation, transport, and controlled release, which is complemented by their biocompatibility, biodegradability, and non-immunogenic nature. Stimuli-responsive hydrogels, also known as smart hydrogels, have strictly regulated release patterns since they respond and adapt based on various external stimuli. Moreover, they can imitate the intrinsic tissues' mechanical, biological, and physicochemical properties. These characteristics allow stimuli-responsive hydrogels to provide cutting-edge, effective, and safe treatment. Constant progress in the field necessitates an up-to-date summary of current trends and breakthroughs in the biomedical application of stimuli-responsive chitosan-based hydrogels, which was the aim of this review. General data about hydrogels sensitive to ions, pH, redox potential, light, electric field, temperature, and magnetic field are recapitulated. Additionally, formulations responsive to multiple stimuli are mentioned. Focusing on chitosan-based smart hydrogels, their multifaceted utilization was thoroughly described. The vast application spectrum encompasses neurological disorders, tumors, wound healing, and dermal infections. Available data on smart chitosan hydrogels strongly support the idea that current approaches and developing novel solutions are worth improving. The present paper constitutes a valuable resource for researchers and practitioners in the currently evolving field.

Meckel's Diverticulum Injuries after Blunt Trauma.

Background: The complications associated with Meckel's diverticulum (MD) are well-known. However, blunt injuries regarding MD have not been widely described in the literature. This was the reason for undertaking research on MD lesions. Materials and Methods: The materials consisted of 28 cases of damage to MD after blunt trauma published during the years 1921-2022. The collected data were subjected to statistical analysis. Results: The following MD injuries have been identified, starting with the most common isolated perforation of MD, bleeding from the area of MD, perforation of MD with concomitant tearing of the mesentery intestines and bleeding, intussusception of MD, and intramural hematoma of MD with adjacent mesenteric hematoma. Most injuries were caused by a traffic accident, followed by sports, accidents at work, and then violence. Almost all the cases (27) involved men. Several possible mechanisms may contribute to post-traumatic damage to MD. First of all, they are associated with abdominal compression and a secondary increase in intra-abdominal pressure as well as with the action of shearing forces during deceleration. Conclusions: Traumatic MD injuries are differentiated and very rare. They can coexist with other serious injuries to the abdominal organs.

Carboxymethyl Chitosan Hydrogels for Effective Wound Healing-An Animal Study.

Hydrogels have various applications in medicine, for example, in systems for controlled drug release or as wound dressings, where they provide an appropriate environment for healing and constitute a barrier to microorganisms. The aim of this study was to evaluate the action of carboxymethyl chitosan (CMCS) hydrogels in wound healing therapy in vivo using a laboratory rat model. The hydrogels were formed from aqueous solutions of a CMCS biopolymer via electron beam irradiation, with the presence of a crosslinking agent of poly(ethylene glycol) diacrylate. A histopathological examination of injured tissue, using a model of a hard-to-heal wound, indicated that the CMCS hydrogel supported healing. The new gel dressing, being noncytotoxic, presents great potential in wound treatment, with positive effects on the amount of inflammatory infiltration, young collagen formation, and the degree of epidermalization. A key advantage of the current approach (i.e., using competitive radiation technology for synthesis) is that it includes only one step, with the product being sterilized as it is synthesized. The hydrogel effectively supports wound healing and can serve as a bio-based and biodegradable platform for other medical applications.

The artificial oxygen carrier erythrocruorin-characteristics and potential significance in medicine.

The diminishing supply and increasing costs of donated blood have motivated research into novel hemoglobin-based oxygen carriers (HBOCs) that can serve as red blood cell (RBC) substitutes. HBOCs are versatile agents that can be used in the treatment of hemorrhagic shock. However, many of the RBC substitutes that are based on mammalian hemoglobins have presented key limitations such as instability and toxicity. In contrast, erythrocruorins (Ecs) are other types of HBOCs that may not suffer these disadvantages. Ecs are giant metalloproteins found in annelids, crustaceans, and some other invertebrates. Thus far, the Ecs of Lumbricus terrestris (LtEc) and Arenicola marina (AmEc) are the most thoroughly studied. Based on data from preclinical transfusion studies, it was found that these compounds not only efficiently transport oxygen and have anti-inflammatory properties, but also can be modified to further increase their effectiveness. This literature review focuses on the structure, properties, and application of Ecs, as well as their advantages over other HBOCs. Development of methods for both the stabilization and purification of erythrocruorin could confer to enhanced access to artificial blood resources.

Biocompatibility and Mechanical Properties of Carboxymethyl Chitosan Hydrogels.

Hydrogels have the properties of solid substances and are useful for medicine, e.g., in systems for the controlled release of drugs or as wound dressings. They isolate the wound from the external environment and constitute a barrier to microorganisms while still being permeable to oxygen. In the current study, hydrogels were formed from concentrated aqueous solutions of carboxymethyl chitosan (CMCS) via electron beam irradiation, with the presence of a crosslinking agent: poly(ethylene glycol)diacrylate. The aim of the study was to compare the properties and action of biopolymer CMCS hydrogels with commercial ones and to select the best compositions for future research towards wound-dressing applications. The elasticity of the gel depended on the component concentrations and the irradiation dose employed to form the hydrogel. Young's modulus for the tested hydrogels was higher than for the control material. The Live/Dead test performed on human fibroblasts confirmed that the analyzed hydrogels are not cytotoxic, and for some concentrations, they cause a slight increase in the number of cells compared to the control. The biocompatibility studies carried out on laboratory rats showed no adverse effect of hydrogels on animal tissues, confirming their biocompatibility and suggesting that CMCS hydrogels could be considered as wound-healing dressings in the future. Ionizing radiation was proven to be a suitable tool for CMCS hydrogel synthesis and could be of use in wound-healing therapy, as it may simultaneously sterilize the product.

Biological assessment of new tetrahydroacridine derivatives with fluorobenzoic moiety in vitro on A549 and HT-29 cell lines and in vivo on animal model.

A new series of tetrahydroacridine derivatives with the fluorobenzoyl moiety was synthesized and evaluated for cytotoxic activity against lung cancer cell lines A549 and colorectal cancer HT29. The cytotoxic activity of the compounds was compared on the somatic cell line-EAhy926. Compounds showed high cytotoxic activity on A549 cells (IC50 183.26-68.07 µM) and HT29 cells (IC50 68.41-19.70 µM), higher than controls-etoposide (IC50 451.47 µM) toward A549 and 5-fluorouracil (IC50 1626.85 µM) against HT29. Derivative 4 was the most cytotoxic to A549, whereas for the cell lines HT29 compound 6. Selected compounds showed similar cytotoxicity to the EAhy926 cell line (IC50 about 50 µM). In the hyaluronidase inhibition assay, all compounds exhibited anti-inflammatory activity, including 4 exhibiting the best inhibitory activity-IC50 of 52.27 µM when the IC50 heparin was 56.41 µM. Mathematical modeling was performed to determine LD50 after intraperitoneal, oral, intravenous and subcutaneous administration and to predict potential mutagenicity and carcinogenicity of the compounds analyzed. Obtained results showed that tested derivatives are slightly toxic compounds, and LD50 values (mg/kg) ranged from 680 to 1200 (oral rat model), the analyzed compounds have low mutagenic potential, and differences between derivatives are insignificant and very low probability of carcinogenicity. To confirm mathematical calculations, an in vivo test was carried out on a laboratory mouse model for two selected compounds. It allowed to qualify compounds: 6 to category 4 of the GHS scale, and 4 to category 3 of the GHS scale.

Novel tetrahydroacridine derivatives with iodobenzoic moieties induce G0/G1 cell cycle arrest and apoptosis in A549 non-small lung cancer and HT-29 colorectal cancer cells.

A series of nine tetrahydroacridine derivatives with iodobenzoic moiety were synthesized and evaluated for their cytotoxic activity against cancer cell lines-A549 (human lung adenocarcinoma), HT-29 (human colorectal adenocarcinoma) and somatic cell line-EA.hy926 (human umbilical vein cell line). All compounds displayed high cytotoxicity activity against A549 (IC50 59.12-14.87 µM) and HT-29 (IC50 17.32-5.90 µM) cell lines, higher than control agents-etoposide and 5-fluorouracil. Structure-activity relationship showed that the position of iodine in the substituent in the para position and longer linker most strongly enhanced the cytotoxic effect. Among derivatives, 1i turned out to be the most cytotoxic and displayed IC50 values of 14.87 µM against A549 and 5.90 µM against HT-29 cell lines. In hyaluronidase inhibition assay, all compounds presented anti-inflammatory activity, however, slightly lower than reference compound. ADMET prediction showed that almost all compounds had good pharmacokinetic profiles. 1b, 1c and 1f compounds turned out to act against chemoresistance in cisplatin-resistant 253J B-V cells. Compounds intercalated into DNA and inhibited cell cycle in G0/G1 phase-the strongest inhibition was observed for 1i in A549 and 1c in HT-29. Among compounds, the highest apoptotic effect in both cell lines was observed after treatment with 1i. Compounds caused DNA damage and H2AX phosphorylation, which was detected in A549 and HT-29 cells. All research confirmed anticancer properties of novel tetrahydroacridine derivatives and explained a few pathways of their mechanism of cytotoxic action.

[Tragedy in the Valley Jaworowa: incredible coincidence or perfect murder?]

The paper presents the case of an unexplained and the most mysterious death in the history of Polish Tatra tourism. It concerns three people of different ages and occurred on August 3, 1925 in the Valley of Jaworowa. Kazimierz Kasznica, his son Waclaw Kasznica and a newly discovered mountaineer Ryszard Wasserberger died suddenly for unknown reasons in 15 minutes during a mountain trek. This story is interesting due to the mysterious, simultaneous death of three people of different ages and due to the fact that Waleria Kasznica - the wife of Kazimierz and the mother of Waclaw Kasznica survived the journey. KEY WORDS.