Pain has been considered as a concept of sensation that we feel as a reaction to the stimulus of our surrounding, putting us in harm’s way and acting as a form of defense mechanism that our body has permanently installed into its system. However, pain leads to a huge chunk of finances within the healthcare system with continuous rehabilitation of patients with adverse pain sensations, which might reduce not only their quality of life but also their productivity at work setting back the pace of our economy. It may not look like a huge deal but factor in pain as an issue for majority of us, it becomes an economical burden. Although pain has been researched into and understood by numerous researches, from its definition, mechanism of action to its inhibition in hopes of finding an absolute solution for victims of pain, the pathways of pain sensation, neurotransmitters involved in producing such a sensation are not comprehensively reviewed. Therefore, this review article aims to put in place a thorough understanding of major pain conditions that we experience—nociceptive, inflammatory and physiologically dysfunction, such as neuropathic pain and its modulation and feedback systems. Moreover, the complete mechanism of conduction is compiled within this article, elucidating understandings from various researches and breakthroughs.

The receptor for advanced glycation end products (RAGE) is a transmembrane receptor of the immunoglobulin superfamily, capable of binding a broad repertoire of ligands. RAGE-ligands interaction induces a series of signal transduction cascades and lead to the activation of transcription factor NF-κB as well as increased expression of cytokines, chemokines, and adhesion molecules. These effects endow RAGE with the role in the signal transduction from pathogen substrates to cell activation during the onset and perpetuation of inflammation. RAGE signaling and downstream pathways have been implicated in a wide spectrum of inflammatory-related pathologic conditions such as arteriosclerosis, Alzheimer's disease, arthritis, acute respiratory failure, and sepsis. Despite the significant progress in other RAGE studies, the functional importance of the receptor in clinical situations and inflammatory diseases still remains to be fully realized. In this review, we will summarize current understandings and lines of evidence on the molecular mechanisms through which RAGE signaling contributes to the pathogenesis of the aforementioned inflammation-associated conditions.

Human gut is home to a diverse and complex microbial ecosystem encompassing bacteria, viruses, parasites, fungi, and other microorganisms that have an undisputable role in maintaining good health for the host. Studies on the interplay between microbiota in the gut and various human diseases remain the key focus among many researchers. Nevertheless, advances in sequencing technologies and computational biology have helped us to identify a diversity of fungal community that reside in the gut known as the mycobiome. Although studies on gut mycobiome are still in its infancy, numerous sources have reported its potential role in host homeostasis and disease development. Nonetheless, the actual mechanism of its involvement remains largely unknown and underexplored. Thus, in this review, we attempt to discuss the recent advances in gut mycobiome research from multiple perspectives. This includes understanding the composition of fungal communities in the gut and the involvement of gut mycobiome in host immunity and gut-brain axis. Further, we also discuss on multibiome interactions in the gut with emphasis on fungi-bacteria interaction and the influence of diet in shaping gut mycobiome composition. This review also highlights the relation between fungal metabolites and gut mycobiota in human homeostasis and the role of gut mycobiome in various human diseases. This multiperspective review on gut mycobiome could perhaps shed new light for future studies in the mycobiome research area.

The aim of the present study was to verify the anti-inflammatory activity of Orthosiphon stamineus leaf extracts and to identify the active compound(s) contributing to its anti-inflammatory activity using a developed HPLC method. Active chloroform extract of O. stamineus was fractionated into three fractions using a dry flash column chromatography method. These three fractions were investigated for anti-peritoneal capillary permeability, in vitro nitric oxide scavenging activity, anti-inflammatory and nitric oxide (NO) inhibition using carrageenan-induced hind paw edema method. The flavonoid rich chloroform extract fraction (CF2) [containing sinensetin (2.86% w/w), eupatorin (5.05% w/w) and 3’-hydroxy-5,6,7,4’-tetramethoxyflavone (1.101% w/w)], significantly reduced rat hind paw edema, NO and decreased dye leakage to peritoneal cavity at p < 0.05. IC50 of in vitro NO scavenging of CF2 was 0.3 mg/mL. These results suggest that the anti-inflammatory properties of these CF2 may possibly be due to the presence of flavonoid compounds capable of affecting the NO pathway.

Orthosiphon stamineus (OS), Benth. (Lamiaceae) is widely used in Malaysia for treatments of various kidney and liver ailments. In the experiment, DPPH* radicals scavenging, Fe(3+)-induced lipid peroxidation inhibiting activities and trolox equivalent antioxidant capacity (TEAC) of methanol/water extract of Orthosiphon stamineus (SEOS) were determined. The results indicated that SEOS exhibited antioxidant, lipid peroxidation inhibition and free radical scavenging activities. The hepatoprotective activity of the SEOS was studied using CCl(4)-induced liver toxicity in rats. The activity was assessed by monitoring liver function tests through the measurement of alanine transaminase (ALT) and aspartate transaminase (AST). Furthermore, hepatic tissues were also subjected to histopathological studies. Pretreatment of SEOS (125, 250, 500 and 1000 mg/kg p.o.) dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of serum ALT and AST activities. The results of the present study indicated that the hepatoprotective effect of Orthosiphon stamineus might be ascribable to its antioxidant and free radical scavenging property.