Functionalization of bacterial cellulose: Exploring diverse applications and biomedical innovations: A review.

The demand for the functionalization of additive materials based on bacterial cellulose (BC) is currently high due to their potential applications across various sectors. The preparation of BC-based additive materials typically involves two approaches: in situ and ex situ. In situ modifications entail the incorporation of additive materials, such as soluble and dispersed substances, which are non-toxic and not essential for bacterial cell growth during the production process. However, these materials can impact the yield and self-assembly of BC. In contrast, ex situ modification occurs subsequent to the formation of BC, where the additive materials are not only adsorbed on the surface but also impregnated into the BC pellicle, while the BC slurry was homogenized with other additive materials and gelling agents to create composite films using the casting method. This review will primarily focus on the in situ and ex situ functionalization of BC then sheds light on the pivotal role of functionalized BC in advancing biomedical technologies, wound healing, tissue engineering, drug delivery, bone regeneration, and biosensors.

M1 polarization bias and subsequent nonalcoholic steatohepatitis progression is attenuated by nitric oxide donor DETA NONOate via inhibition of CYP2E1-induced oxidative stress in obese mice.

Activation of M1 macrophages in nonalcoholic steatohepatitis (NASH) is produced by several external or endogenous factors: inflammatory stimuli, oxidative stress, and cytokines are known. However, any direct role of oxidative stress in causing M1 polarization in NASH has been unclear. We hypothesized that CYP2E1-mediated oxidative stress causes M1 polarization in experimental NASH, and that nitric oxide (NO) donor administration inhibits CYP2E1-mediated inflammation with concomitant attenuation of M1 polarization. Because CYP2E1 takes center stage in these studies, we used a toxin model of NASH that uses a ligand and a substrate of CYP2E1 for inducing NASH. Subsequently, we used a methionine and choline-deficient diet-induced rodent NASH model where the role of CYP2E1 in disease progression has been shown. Our results show that CYP2E1 causes M1 polarization bias, which includes a significant increase in interleukin-1ß (IL-1ß) and IL-12 in both models of NASH, whereas CYP2E1-null mice or diallyl sulfide administration prevented it. Administration of gadolinium chloride (GdCl3), a macrophage toxin, attenuated both the initial M1 response and the subsequent M2 response, showing that the observed increase in cytokine levels is primarily from macrophages. Based on the evidence of an adaptive NO increase, the NO donor administration in vivo that mechanistically inhibited CYP2E1 catalyzed the oxidative stress during the entire study in NASH-abrogated M1 polarization and NASH progression. The results obtained show the association of CYP2E1 in M1 polarization, and that inhibition of CYP2E1 catalyzed oxidative stress by an NO donor (DETA NONOate [(Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate]) can be a promising therapeutic strategy in NASH.

The angiopietin-1-Tie2 pathway prevents rather than promotes pulmonary arterial hypertension in transgenic mice.

The role of the angiopoietin-1 (Ang1)-Tie2 pathway in the pathogenesis of pulmonary arterial hypertension (PAH) is controversial. Although Ang1 is well known to prevent endothelial activation and injury in systemic vascular beds, this pathway has been suggested to mediate pulmonary vascular remodeling in PAH. Therefore, we used transgenic models to determine the effect of increased or decreased Tie2 activity on the development of PAH. We now report modest spontaneous elevation in right ventricular systolic pressure in Tie2-deficient mice (Tie2(+/-)) compared with wild-type (WT) littermate controls, which was exacerbated upon chronic exposure to the clinically relevant PAH triggers, serotonin (5-HT) or interleukin-6 (IL-6). Moreover, overexpression of Ang1 in transgenic mice had no deleterious effect on pulmonary hemodynamics and, if anything, blunted the response to 5-HT. Exposure to 5-HT or IL-6 also decreased lung Ang1 expression, further reducing Tie2 activity and inducing pulmonary apoptosis in the Tie2(+/-) group only. Similarly, cultured pulmonary artery endothelial cells subjected to Tie2 silencing demonstrated increased susceptibility to apoptosis after 5-HT treatment. Finally, treatment of Tie2-deficient mice with Z-VAD, a pan-caspase inhibitor, prevented the pulmonary hypertensive response to 5-HT. Thus, these findings firmly establish that endothelial survival signaling via the Ang1-Tie2 pathway is protective in PAH.

Regulation of proliferation and membrane potential by chloride currents in rat pulmonary artery smooth muscle cells.

Pulmonary artery smooth muscle cell (PASMC) proliferation contributes to increased pulmonary vascular resistance and pulmonary hypertension. Because proliferation depends on membrane potential (V(m)) and because V(m) is, in part, determined by Cl(-) currents (I(Cl)), we examined the effects of I(Cl) inhibition with 4,4;-diisothiocyanatostilbene-2,2;-disulfonic acid (DIDS) on cultured rat PASMCs. DIDS (30 mumol/L) reduced cell numbers, decreased 5-bromodeoxyuridine incorporation and delayed cell cycle progression. I(Cl) inhibition with 5-Nitro-2-(3-phenylpropylamino) benzoic acid (100 mumol/L) also reduced cell numbers of cultured rat PASMCs. To test the possible involvement of I(Cl) in the regulation of PASMC proliferation, we measured V(m) and I(Cl) in both cultured (proliferating) and acutely dissociated (nonproliferating) rat PASMCs. V(m) (-39.3+/-1.4 mV) was close to the equilibrium potential of Cl(-) (-39 mV) in proliferating PASMCs but differed from equilibrium potential of Cl(-) in acutely dissociated cells (-45.3+/-0.9 mV). DIDS and substitution of extracellular Cl(-) with I(-) induced V(m) hyperpolarization in proliferating but not nonproliferating PASMCs. Consistent with V(m) recordings, DIDS-sensitive baseline and swelling-activated (Ca(2+)-independent) I(Cl)s, recorded with low Ca(2+) (<1 nmol/L) pipette solutions, were approximately 5-fold greater in proliferating than in nonproliferating PASMCs. By contrast, Ca(2+)-activated I(Cl) did not differ between proliferating and nonproliferating PASMCs. Ca(2+)-independent I(Cl)s were also increased in proliferating PASMCs acutely dissociated from rats exposed to hypoxia (10% O(2); 7 days). These findings are consistent with the conclusion that I(Cl)s regulate proliferation of PASMCs and suggest that selective I(Cl) inhibition may be useful in treating pulmonary hypertension.

Oxygen regulation of arterial smooth muscle cell proliferation and survival.

The purpose of this study was to determine if hypoxia elicits different proliferative and apoptotic responses in systemic arterial smooth muscle cells incubated under conditions that do or do not result in cellular ATP depletion and whether these effects are relevant to vascular remodeling in vivo. Gene expression profiling was used to identify potential regulatory pathways. In human aortic smooth muscle cells (HASMCs) incubated at 3% O(2), proliferation and progression through the G1/S interphase are enhanced. Incubation at 1% O(2) reduced proliferation, delayed G1/S transition, increased apoptotic cell death, and is associated with mitochondrial membrane depolarization and reduced cellular ATP levels. In aorta and mesenteric artery from rats exposed to hypoxia (10% O(2), 48 h), both proliferation and apoptosis are increased, as are medial nuclear density and smooth muscle cell content. Although nuclear levels of hypoxia-inducible factor 1-alpha (HIF-1alpha) are increased to a similar extent in HASMCs incubated at 1 and 3% O(2), expression of tumor protein p53, its transcriptional target p21, as well as their regulatory factors and downstream effectors, are differentially affected under these two conditions, suggesting that the bidirectional effects of hypoxia are mediated by this pathway. We conclude that hypoxia induces a state of enhanced cell turnover through increased rates of both smooth muscle cell proliferation and death. This confers the ability to remodel the vasculature in response to changing tissue metabolic needs while avoiding the accumulation of mutations that may lead to malignant transformation or the formation of abnormal vascular structures.