Stem cell biotherapy: A new remedy for Trichinella spiralis-induced inflammatory myopathy.

Trichinella spiralis (T. spiralis)-induced myopathy is an inflammatory myopathy that is difficult to treat unless the parasite is combated in its early intestinal phase before it reaches the muscles. This study aimed to evaluate the effect of local mesenchymal stem cell (MSC) therapy on T. spiralis-induced inflammatory myopathy in rats. Rats were divided into four groups: Group 1 (non-infected non-treated group); Group 2 (infected non-treated group); Group 3 (infected albendazole (ABZ)-treated group); and Group 4 (infected MSC-treated group). Their muscle status was assessed physiologically with the righting reflex and electromyography (EMG), parasitologically with the total muscle larval count, histopathologically with hematoxylin and eosin and Mallory's trichrome stains, as well as immunohistochemically for myogenin as a marker of muscle regeneration. Additionally, serum muscle enzymes creatine kinase (CK) and lactate dehydrogenase (LDH), as well as muscle matrix metalloproteinases MMP1 and MMP9, were assayed. Finally, the immunological response was assessed by measuring the levels of the muscle inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ), and interleukin-4 (IL-4). Our findings revealed that MSC therapy markedly improved muscle EMG and righting reflex, as well as the histopathological appearance of the muscles, reduced inflammatory cellular infiltrates, and increased myogenin immunostaining. It also reduced serum CK and LDH levels, as well as muscle INF-γ, TNF-α, IL-4, MMP1, and MMP9 levels. However, it had no effect on the total muscle larval count. Accordingly, due to its anti-inflammatory properties and muscle-regenerative effect, MSC therapy could be a promising new remedy for T. spiralis-induced myopathy.

Bevacizumab: A new take on therapy of muscle phase of Trichinella spiralis infection.

Trichinellosis is a zoonosis that causes health and economic problems worldwide. The available therapy is far from perfect as the conventional drugs used against Trichinella spiralis (T. spiralis) are active against the intestinal adult parasites but much less active against encapsulated larvae in muscles. Therefore, this work aimed to evaluate the effect of the anti-angiogenic agent, bevacizumab, on the muscle larvae of T. spiralis. For this aim, T. spiralis-infected mice were treated by two different doses of bevacizumab, thereafter larval counts as well as biochemical and pathological changes were evaluated in the muscles. The larval burden was reduced in the muscles of treated mice, denoting a detrimental effect of bevacizumab against encapsulated Trichinella larvae. Moreover, there was marked improvement of muscle inflammation with the treatment, evidenced by reduction of the proinflammatory cytokines (IL-6 and TNF-α) and regression of the inflammatory infiltrates in histological sections. Amelioration of oxidative stress in the muscle was also observed in treated animals with reduction of malondialdehyde and carbonic anhydrase III and increase in superoxide dismutase levels. Finally, the treatment induced downregulation of the expression of VEGF and CD31, denoting suppressed angiogenesis. All these beneficial effects were found to be dose dependent. In conclusion, bevacizumab exhibited anthelmintic, anti-inflammatory, antioxidant, and anti-angiogenic activities against Trichinella during the muscular phase of infection. Therefore, bevacizumab could be considered as a useful adjuvant treatment in the late stages of trichinellosis.

Syphacia muris infection in rats attenuates colorectal carcinogenesis through oxidative stress and gene expression alterations. Implications for modulatory effects by Bryostatin-1.

Accumulating evidence suggest that some infectious agents may interfere in the natural progression of neoplasia. This study examined the association between chronic infection with adult Syphacia muris parasites and 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis in rats. In addition, the conceivable therapeutic effect of Bryostatin-1, a potent extract of the marine Bryozoan, Bugulane ritina, was investigated against this combined effect.DMH administration has induced aberrant crypt foci (ACF), surrogate biomarkers for colorectal carcinogenesis, while the S. muris infection combined with DMH has significantly increased the total numbers of ACF. Nonetheless, treatment with Bryostatin-1 after infection has significantly reduced the ACF numbers particularly larger ones. This inhibition was concomitant with significant inhibition in the immunohistochemical levels of the ki67, Caspase-3 and IgM levels in colorectal epithelium, as well as serum levels of IgM and IgG. Additionally, treatment with Bryostatin-1 after S. muris + DMH has modulated enzymatic antioxidative markers levels of superoxide dismutase and catalase as well as the non-enzymatic antioxidant markers levels of reduced glutathione, lipid peroxidation, nitric oxide and total antioxidant capacity. Further, treatment with Bryostatin-1 has down-regulated the mRNA expression levels of COX-2 and APC genes in colorectal mucosa. In conclusion, infection with S. muris during colorectal carcinogenesis has significantly modulated the oxidative stress markers in the colorectum, while treatment with Bryostatin-1 has exerted significant curative potential. A mechanism could be explained that Bryostatin-1 treatment has reduced oxidative stress markers activities along with affecting host to parasite immunity possibly leading to changes in the COX-2 and APC expression, retarding cellular proliferation and subsequently reducing the colorectal carcinogenesis events.